Publications by authors named "Vincenzo Cuomo"

89 Publications

[Primary hyperoxaluria: case report and therapeutic perspectives].

G Ital Nefrol 2020 Feb 12;37(1). Epub 2020 Feb 12.

UOSD Nefrologia e dialisi, P.O. Piedimonte Matese, Azienda Sanitaria Locale Caserta.

Primary hyperoxaluria (PH) is a rare genetic disorder with autosomal recessive transmission, characterized by high endogenous production and markedly excessive urinary excretion of oxalate (Ox). It causes the accumulation of calcium oxide crystals in organs and tissues including bones, heart, arteries, skin and kidneys, where it may cause oxalo-calcic nephrolithiasis, nephrocalcinosis and chronic renal failure. Some forms are secondary to enteric diseases, drugs or dietetic substances, while three primitive forms, caused by various enzymatic defects, are currently known: PH1, PH2 and PH3. An early diagnosis, with the aid of biochemical and genetic investigations, helps prevent complications and establish a therapeutic strategy that often includes liver and liver-kidney transplantation, improving the prognosis of these patients. In this work we describe the clinical case of a patient with PH1 undergoing extracorporeal hemodialysis treatment and we report the latest research results that could change the life of patients with PH.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2020

The Heme Oxygenase/Biliverdin Reductase System as Effector of the Neuroprotective Outcomes of Herb-Based Nutritional Supplements.

Front Pharmacol 2019 11;10:1298. Epub 2019 Nov 11.

Institute of Pharmacology, Università Cattolica del Sacro Cuore, Roma, Italy.

Over the last few years, several preclinical studies have shown that some herbal products, such as ferulic acid, , and resveratrol, exert neuroprotective effects through the modulation of the heme oxygenase/biliverdin reductase system. Unfortunately, sufficient data supporting the shift of knowledge from preclinical studies to humans, particularly in neurodegenerative diseases, are not yet available in the literature. The purpose of this review is to summarize the studies and the main results achieved on the potential therapeutic role of the interaction between the heme oxygenase/biliverdin reductase system with ferulic acid, , and resveratrol. Some critical issues have also been reported, mainly concerning the safety profile and the toxicological associated to the supplementation with the herbs mentioned above, based on both current literature and specific reports issued by the competent Regulatory Authorities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2019.01298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859463PMC
November 2019

Ketamine administration induces early and persistent neurochemical imbalance and altered NADPH oxidase in mice.

Prog Neuropsychopharmacol Biol Psychiatry 2020 01 22;96:109750. Epub 2019 Aug 22.

Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, Piazzale Aldo Moro, 5, 00185 Rome, Italy. Electronic address:

Administration in adulthood of subanaesthetic doses of ketamine, an NMDA receptor (NMDA-R) antagonist, is commonly used to induce psychotic-like alterations in rodents. The NADPH oxidase (NOX) derived-oxidative stress has been shown to be implicated in ketamine-induced neurochemical dysfunctions and in the loss of parvalbumin (PV)-positive interneurons associated to the administration of this NMDA receptor antagonist in adult mice. However, very few data are available on the effects of early ketamine administration and its contribution to the development of long-term dysfunctions leading to psychosis. Here, by administering a subanaesthetic dose of ketamine (30 mg/kg i.p.) to mice at postnatal days (PNDs) 7, 9 and 11, we aimed at investigating early neurochemical and oxidative stress-related alterations induced by this NMDA-R antagonist in specific brain regions of mice pups, i.e. prefrontal cortex (PFC) and nucleus accumbens (NAcc) and to assess whether these alterations lasted until the adult period. To this purpose, we evaluated glutamatergic, glutamine and GABAergic tissue levels, as well as PV amount in the PFC, both two hours after the last ketamine injection (PND 11) and at 10  weeks of age. Dopamine (DA) tissue levels and DA turnover were also evaluated in the NAcc at the same time points. Levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a reliable biomarker of oxidative stress, as well as of the free radical producers NOX1 and NOX2 enzymes, were also assessed in both PFC and NAcc of ketamine-treated pups and adult mice. Ketamine-treated pups showed increased cortical levels of glutamate (GLU) and glutamine, as well as similar GABA amount compared to controls, together with an early reduction of cortical PV levels. In the adult period, the same was observed for GLU and PV, whereas GABA levels were increased and no changes in glutamine amount were detected. Ketamine administration in early life induced a decrease in DA tissue levels and an increase of DA turnover which were also detectable at 10 weeks of age. These alterations were accompanied by 8-OHdG elevations in both PFC and NAcc at the two considered life stages. The expression of NOX1 was significantly reduced in these brain regions following ketamine administration at early life stages, while, in the adult period, significant elevation of this enzyme was observed. Levels of NOX2 were found increased at both time points. Our results suggest that an early increase of NOX2-derived oxidative stress may contribute to the development of neurochemical imbalance in PFC and NAcc, induced by ketamine administration. Modifications of NOX1 expression might represent, instead, an early response of the developing brain to a neurotoxic insult, followed by a later attempt to counterbalance ketamine-related detrimental effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pnpbp.2019.109750DOI Listing
January 2020

Curcumin and Heme Oxygenase: Neuroprotection and Beyond.

Int J Mol Sci 2019 May 16;20(10). Epub 2019 May 16.

Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.

Curcumin is a natural polyphenol component of , which is currently considered one of the most effective nutritional antioxidants for counteracting free radical-related diseases. Several experimental data have highlighted the pleiotropic neuroprotective effects of curcumin, due to its activity in multiple antioxidant and anti-inflammatory pathways involved in neurodegeneration. Although its poor systemic bioavailability after oral administration and low plasma concentrations represent restrictive factors for curcumin therapeutic efficacy, innovative delivery formulations have been developed in order to overwhelm these limitations. This review provides a summary of the main findings involving the heme oxygenase/biliverdin reductase system as a valid target in mediating the potential neuroprotective properties of curcumin. Furthermore, pharmacokinetic properties and concerns about curcumin's safety profile have been addressed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20102419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567096PMC
May 2019

[The unusual couple: a clinical case of coexistence between aHUS and Fabry's disease].

G Ital Nefrol 2019 Feb;36(1)

Professore Ordinario di Nefrologia, Università degli Studi della Campania, Luigi Vanvitelli.

Atypical hemolytic-uremic syndrome (aHUS) is a rare, potentially lethal (1-4) systemic disorder, capable of affecting both adults and children, causing thrombotic microangiopathy (TMA) (5) that leads to the formation of thrombus within small blood vessels with multiple organ failure. The pathogenesis of the aHUS is part of a sort of chronic and uncontrolled activation of the complement system by genetic mutation of some proteins usually responsible for its self-regulation (6,7). Today, the rapid diagnosis of the disease and the timely start of treatment with eculizumab, improve outcomes of renal failure, stroke and heart attack (8-10). Fabry disease is a rare tesaurismosis, X linked, due to the deficiency of the lysosomal enzyme alpha-galactosidase A (11-13), necessary for the physiological catabolism of glycosphingolipids. Multisystem clinical manifestations lead to a serious degenerative pathology. The diagnostic suspicion based on anamnesis and careful research of the symptoms and then confirmed by the enzymatic dosage of alpha galactosidase or by molecular analysis, allows the early treatment of the patient with enzyme replacement therapy, guaranteeing the resolution and/or slowing down the evolution of the disease, especially in the brain, heart and kidneys. In this report, we describe the clinical case of a patient who is a carrier of both rare diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2019

The Visible Burrow System: A behavioral paradigm to assess sociability and social withdrawal in BTBR and C57BL/6J mice strains.

Behav Brain Res 2018 05 7;344:9-19. Epub 2018 Feb 7.

Groningen Institute for Evolutionary Life Science, University of Groningen, Nijenborgh 7, 9747 AG, Groningen, The Netherlands. Electronic address:

Disrupted sociability and consequent social withdrawal are (early) symptoms of a wide variety of neuropsychiatric diseases, such as schizophrenia, autism spectrum disorders, depressive disorders and Alzheimer's disease. The paucity of objective measures to translationally assess social withdrawal characteristics has been an important limitation to study this behavioral phenotype, both in human and rodents. The aim of the present study was to investigate sociability and social withdrawal in rodents using an ethologically valid behavioral paradigm, the Visible Burrow System (VBS). The VBS mimics a natural environment, with male and female rodents housed together in an enclosure where a large open arena is connected to a continuously dark burrow system that includes 4 nest boxes. In this study, mixed-sex colonies of C57BL/6J and of BTBR mice have been investigated (n = 8 mice per colony). Results showed marked differences between the two strains, in terms of sociability as well as social withdrawal behaviors. In particular, BTBR mice performed less social behaviors and have a preference for non-social behaviors compared to C57BL/6J mice. Neurobiologically, the decreased sociability of BTBR was accompanied by reduced GABA and increased glutamate concentrations in brain prefrontal cortex (PFC) and amygdala regions. In conclusion, our study validated the use of the VBS as an ethologically relevant behavioral paradigm in group-housed mice to investigate individual sociability and social withdrawal features and their underlying neurobiology. This paradigm may provide new insights to develop new therapeutic treatments for behavioral dysfunctions that may be relevant across neuropsychiatric diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2018.02.003DOI Listing
May 2018

Celecoxib Prevents Cognitive Impairment and Neuroinflammation in Soluble Amyloid β-treated Rats.

Neuroscience 2018 02 3;372:58-73. Epub 2018 Jan 3.

Dept. of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. Electronic address:

Recent findings suggest that soluble forms of amyloid-β (sAβ) peptide contribute to synaptic and cognitive dysfunctions in early stages of Alzheimer's disease (AD). On the other hand, neuroinflammation and cyclooxygenase-2 (COX-2) enzyme have gained increased interest as key factors involved early in AD, although the signaling pathways and pathophysiologic mechanisms underlying a link between sAβ-induced neurotoxicity and inflammation are still unclear. Here, we investigated the effects of selective COX-2 enzyme inhibition on neuropathological alterations induced by sAβ administration in rats. To this purpose, animals received an intracerebroventricular (icv) injection of predominantly monomeric forms of sAβ and, 7 days after, behavioral as well as biochemical parameters and neurotransmitter alterations were evaluated. During this period, rats also received a sub-chronic treatment with celecoxib. Biochemical results demonstrated that icv sAβ injection significantly increased both COX-2 and pro-inflammatory cytokines expression in the hippocampus (Hipp) of treated rats. In addition, the number of hypertrophic microglial cells and astrocytes were upregulated in sAβ-treated group. Interestingly, rats treated with sAβ showed long-term memory deficits, as confirmed by a significant reduction of discrimination index in the novel object recognition test, along with reduced brain-derived neurotrophic factor expression and increased noradrenaline levels in the Hipp. Systemic administration of celecoxib prevented behavioral dysfunctions, as well as biochemical and neurotransmitter alterations. In conclusion, our results suggest that sAβ neurotoxicity might be associated to COX-2-mediated inflammatory pathways and that early treatment with selective COX-2 inhibitor might provide potential remedies to counterbalance the sAβ-induced effects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2017.12.046DOI Listing
February 2018

The contribution of transgenic and nontransgenic animal models in Alzheimer's disease drug research and development.

Behav Pharmacol 2017 04;28(2 and 3-Spec Issue):95-111

aDepartment of Physiology and Pharmacology, Sapienza University of Rome bInstitute of Pharmacology, Catholic University School of Medicine, Rome, Italy.

Over the last few years, several papers have become available in the literature on both the main hallmarks of Alzheimer's disease (AD) and the several intracellular pathways whose alteration is responsible for its onset and progression. The use of transgenic and nontransgenic animal models has played a key role in achieving such a remarkable amount of preclinical data, allowing researchers to dissect the cellular changes occurring in the AD brain. In addition, the huge amount of preclinical evidence arising from these animal models was necessary for the further clinical development of pharmacological agents capable of interfering with most of the impaired neural pathways in AD patients. In this respect, a significant role is played by the dysfunction of excitatory and inhibitory neurotransmission responsible for the cognitive and behavioral symptoms described in AD patients. The aim of this review is to summarize the main animal models that contributed toward unraveling the pathological changes in neurotransmitter synthesis, release, and receptor binding in AD preclinical studies. The review also provides an updated description of the current pharmacological agents - still under clinical development - acting on the neurotransmitter systems.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/FBP.0000000000000296DOI Listing
April 2017

Long-lasting alterations of hippocampal GABAergic neurotransmission in adult rats following perinatal Δ-THC exposure.

Neurobiol Learn Mem 2017 Mar 16;139:135-143. Epub 2017 Jan 16.

Department of Life Sciences and Biotechnology, University of Ferrara, Italy; LTTA Centre, University of Ferrara, Ferrara, Italy. Electronic address:

The long-lasting effects of gestational cannabinoids exposure on the adult brain of the offspring are still controversial. It has already been shown that pre- or perinatal cannabinoids exposure induces learning and memory disruption in rat adult offspring, associated with permanent alterations of cortical glutamatergic neurotransmission and cognitive deficits. In the present study, the risk of long-term consequences induced by perinatal exposure to cannabinoids on rat hippocampal GABAergic system of the offspring, has been explored. To this purpose, pregnant rats were treated daily with Delta-tetrahydrocannabinol (Δ-THC; 5mg/kg) or its vehicle. Perinatal exposure to Δ-THC induced a significant reduction (p<0.05) in basal and K-evoked [H]-GABA outflow of 90-day-old rat hippocampal slices. These effects were associated with a reduction of hippocampal [H]-GABA uptake compared to vehicle exposed group. Perinatal exposure to Δ-THC induced a significant reduction of CB1 receptor binding (B) in the hippocampus of 90-day-old rats. However, a pharmacological challenge with either Δ-THC (0.1μM) or WIN55,212-2 (2μM), similarly reduced K-evoked [H]-GABA outflow in both experimental groups. These reductions were significantly blocked by adding the selective CB1 receptor antagonist SR141716A. These findings suggest that maternal exposure to cannabinoids induces long-term alterations of hippocampal GABAergic system. Interestingly, previous behavioral studies demonstrated that, under the same experimental conditions as in the present study, perinatal cannabinoids exposure induced cognitive impairments in adult rats, thus resembling some effects observed in humans. Although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of hippocampus aminoacidergic transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users, is supported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nlm.2016.12.023DOI Listing
March 2017

Ferulic Acid Improves Cognitive Skills Through the Activation of the Heme Oxygenase System in the Rat.

Mol Neurobiol 2018 02 12;55(2):905-916. Epub 2017 Jan 12.

Institute of Pharmacology, Catholic University School of Medicine, Rome, Italy.

Over the last years, many studies reported on the antioxidant effects of ferulic acid (FA) in preclinical models of dementia through the activation of the heme oxygenase/biliverdin reductase (HO/BVR) system. However, only a few studies evaluated whether FA could improve neurological function under milder conditions, such as psychological stress. The aim of this study was to investigate the effects of FA (150 mg/kg intraperitoneal route) on cognitive function in male Wistar rats exposed to emotional arousal. Animals were randomly assigned to two experimental groups, namely not habituated or habituated to the experimental context, and the novel object recognition test was used to evaluate their cognitive performance. The administration of FA significantly increased long-term retention memory in not habituated rats. Ferulic acid increased the expression of HO-1 in the hippocampus and frontal cortex of not habituated rats only, whereas HO-2 resulted differently modulated in these cognitive brain areas. No significant effects on either HO-1 or HO-2 or BVR were observed in the cerebellum of both habituated and not habituated rats. Ferulic acid activated the stress axis in not habituated rats, as shown by the increase in hypothalamic corticotrophin-releasing hormone levels. Pre-treatment with Sn-protoporphyrin-IX [0.25 μmol/kg, intracerebroventricular route (i.c.v.)], a well-known inhibitor of HO activity through which carbon monoxide (CO) and biliverdin (BV) are generated, abolished the FA-induced improvement of cognitive performance only in not habituated rats, suggesting a role for HO-derived by-products. The CO-donor tricarbonyldichlororuthenium (II) (30 nmol/kg i.c.v.) mimicked the FA-related improvement of cognitive skills only in not habituated rats, whereas BV did not have any effect in any group. In conclusion, these results set the stage for subsequent studies on the neuropharmacological action of FA under conditions of psychological stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-017-0381-1DOI Listing
February 2018

Interacting Cannabinoid and Opioid Receptors in the Nucleus Accumbens Core Control Adolescent Social Play.

Front Behav Neurosci 2016 16;10:211. Epub 2016 Nov 16.

Institut National De La Santé Et De La Recherche Médicale U901Marseille, France; Université de la Méditerranée UMR S901 Aix-Marseille 2Marseille, France; INMEDMarseille, France.

Social play behavior is a highly rewarding, developmentally important form of social interaction in young mammals. However, its neurobiological underpinnings remain incompletely understood. Previous work has suggested that opioid and endocannabinoid neurotransmission interact in the modulation of social play. Therefore, we combined behavioral, pharmacological, electrophysiological, and genetic approaches to elucidate the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) in social play, and how cannabinoid and opioid neurotransmission interact to control social behavior in adolescent rodents. Systemic administration of the 2-AG hydrolysis inhibitor JZL184 or the opioid receptor agonist morphine increased social play behavior in adolescent rats. These effects were blocked by systemic pretreatment with either CB1 cannabinoid receptor (CB1R) or mu-opioid receptor (MOR) antagonists. The social play-enhancing effects of systemic morphine or JZL184 treatment were also prevented by direct infusion of the CB1R antagonist SR141716 and the MOR antagonist naloxone into the nucleus accumbens core (NAcC). Searching for synaptic correlates of these effects in adolescent NAcC excitatory synapses, we observed that CB1R antagonism blocked the effect of the MOR agonist DAMGO and, conversely, that naloxone reduced the effect of a cannabinoid agonist. These results were recapitulated in mice, and completely abolished in CB1R and MOR knockout mice, suggesting that the functional interaction between CB1R and MOR in the NAcC in the modulation of social behavior is widespread in rodents. The data shed new light on the mechanism by which endocannabinoid lipids and opioid peptides interact to orchestrate rodent socioemotional behaviors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2016.00211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110529PMC
November 2016

Chronic Psychosocial Stress Impairs Bone Homeostasis: A Study in the Social Isolation Reared Rat.

Front Pharmacol 2016 8;7:152. Epub 2016 Jun 8.

Department of Experimental and Clinical Medicine, University of Foggia Foggia, Italy.

Chronic psychosocial stress is a key player in the onset and aggravation of mental diseases, including psychosis. Although a strong association between this psychiatric condition and other medical co-morbidities has been recently demonstrated, few data on the link between psychosis and bone homeostasis are actually available. The aim of this study was to investigate whether chronic psychosocial stress induced by 4 or 7 weeks of social isolation in drug-naïve male Wistar rats could alter bone homeostasis in terms of bone thickness, mineral density and content, as well as markers of bone formation and resorption (sclerostin, cathepsin K, and CTX-I). We found that bone mineral density was increased in rats exposed to 7 weeks of social isolation, while no differences were detected in bone mineral content and area. Moreover, 7 weeks of social isolation lead to increase of femur thickness with respect to controls, suggesting the development of a hyperostosis condition. Isolated rats showed no changes in sclerostin levels, a marker of bone formation, compared to grouped animals. Conversely, bone resorption markers were significantly altered after 7 weeks of social isolation in terms of decrease in cathepsin K and increase of CTX-I. No alterations were found after 4 weeks of isolation rearing. Our observations suggest that chronic psychosocial stress might affect bone homeostasis, more likely independently from drug treatment. Thus, the social isolation model might help to identify possible new therapeutic targets to treat the burden of chronic psychosocial stress and to attempt alternative therapy choices.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2016.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896906PMC
July 2016

Lifelong Nutritional Omega-3 Deficiency Evokes Depressive-Like State Through Soluble Beta Amyloid.

Mol Neurobiol 2017 04 29;54(3):2079-2089. Epub 2016 Feb 29.

Physiology and Pharmacology, La Sapienza, University of Rome, Rome, Italy.

Recent evidence pointed out that the prevalence of depression has reached epidemic proportions in last decades. This increase has been linked to many environmental factors, among these the influence of dietary factors has gained great attention. In particular, it has been reported that low n-3 polyunsaturated fatty acid (n-3 PUFA) intake in diet is correlated to the development of depressive and anxiety-like symptoms. Furthermore, maternal malnutrition is a widely accepted risk factor for developing mental illness in later adulthood; among others, depression has been strongly associated to this event. On the other hand, we have previously found that acute intracerebral injection of the soluble beta amyloid 1-42 (Aβ) peptide induces a depressive-like behavior in rats, associated to altered hypothalamic-pituitary-adrenal (HPA) axis activation and reduced cortical serotonin and neurotrophin levels. The aim of the present work was to study the effect of pre- and post-natal (5 weeks post-weaning) exposure to diets differently enriched in n-3, n-6, as well as n-6/n-3 PUFA balanced, on immobility time displayed on the forced swimming test (FST), along with neuroendocrine quantification in offspring rats. Results showed that n-6 PUFA-enriched diet increased depressive- and anxiety-like behaviors, as shown by the elevation in the immobility time in the FST test and self-grooming in the open field test. Those effects were accompanied by reduced cortical serotonin, high plasmatic corticosterone and hypothalamic corticotropin-releasing factor levels. Finally, enhanced plasmatic Aβ levels after n-6 PUFA diet and reduced plasmatic Aβ levels after n-3 PUFA were found. Taken together, our data indicate that Aβ might be crucially involved in behavioral alterations found after n-6 rich PUFA diet and strongly endorse the protective role of n-3 and the detrimental effect of improper n-6 PUFA diet consumption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-016-9809-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355522PMC
April 2017

Early Loss of Blood-Brain Barrier Integrity Precedes NOX2 Elevation in the Prefrontal Cortex of an Animal Model of Psychosis.

Mol Neurobiol 2017 04 24;54(3):2031-2044. Epub 2016 Feb 24.

Department of Physiology and Pharmacology, "Sapienza", University of Rome, Rome, Italy.

The social isolation rearing of young adult rats is a model of psychosocial stress and provides a nonpharmacological tool to study alterations reminiscent of symptoms seen in psychosis. We have previously demonstrated that social isolation in rats leads to increased oxidative stress and to cerebral NOX2 elevations. Here, we investigated early alterations in mRNA expression leading to increased NOX2 in the brain. Rats were exposed to a short period of social isolation (1 week) and real-time polymerase chain reaction (PCR) for mRNA expression of genes involved in blood-brain barrier (BBB) formation and integrity (ORLs, Vof 21 and Vof 16, Leng8, Vnr1, and Trank 1 genes) was performed. Real-time PCR experiments, immunohistochemistry, and Western blotting analysis showed an increased expression of these genes and related proteins in isolated rats with respect to control animals. The expression of specific markers of BBB integrity, such as matrix metalloproteinase 2 (MMP2), matrix metalloproteinase 9 (MMP9), occludin 1, and plasmalemmal vesicle associated protein-1 (PV-1), was also significantly altered after 1 week of social isolation. BBB permeability, evaluated by quantification of Evans blue dye extravasation, as well as interstitial fluid, was significantly increased in rats isolated for 1 week with respect to controls. Isolation-induced BBB disruption was also accompanied by a significant increase of Interleukin 6 (IL-6) expression. Conversely, no differences in NOX2 levels were detected at this time point. Our study demonstrates that BBB disruption precedes NOX2 elevations in the brain. These results provide new insights in the interplay of mechanisms linking psychosocial stress to early oxidative stress in the brain, disruption of the BBB, and the development of mental disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-016-9791-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5355521PMC
April 2017

Soluble beta amyloid evokes alteration in brain norepinephrine levels: role of nitric oxide and interleukin-1.

Front Neurosci 2015 5;9:428. Epub 2015 Nov 5.

Department of Clinical and Experimental Medicine, University of Foggia Foggia, Italy.

Strong evidence showed neurotoxic properties of beta amyloid (Aβ) and its pivotal role in the Alzheimer's disease (AD) pathogenesis. Beside, experimental data suggest that Aβ may have physiological roles considering that such soluble peptide is produced and secreted during normal cellular activity. There is now suggestive evidence that neurodegenerative conditions, like AD, involve nitric oxide (NO) in their pathogenesis. Nitric oxide also possess potent neuromodulatory actions in brain regions, such as prefrontal cortex (PFC), hippocampus (HIPP), and nucleus accumbens (NAC). In the present study, we evaluated the effect of acute Aβ injection on norepinephrine (NE) content before and after pharmacological manipulations of nitrergic system in above mentioned areas. Moreover, effects of the peptide on NOS activity were evaluated. Our data showed that 2 h after i.c.v. soluble Aβ administration, NE concentrations were significantly increased in the considered areas along with increased iNOS activity. Pre-treatment with NOS inhibitors, 7-Nitroindazole (7-NI), and N6-(1-iminoethyl)-L-lysine-dihydrochloride (L-NIL), reversed Aβ-induced changes. Ultimately, pharmacological block of interleukin1 (IL-1) receptors prevented NE increase in all brain regions. Taken together our findings suggest that NO and IL-1 are critically involved in regional noradrenergic alterations induced by soluble Aβ injection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnins.2015.00428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633524PMC
November 2015

"Natural" relief of pregnancy-related symptoms and neonatal outcomes: above all do no harm.

J Ethnopharmacol 2015 Nov;174:396-402

Department of Physiology and Pharmacology, Sapienza, University of Rome, Rome 00185, Italy.

Ethnopharmacological Relevance: In the South of Italy the use of herbal remedies to alleviate pregnancy-related symptoms is very common.

Objectives: To investigate the proportion, prevalence of use, attitude and knowledge base in a sample of Italian pregnant women in the South of Italy. To explore the possible influence and risks of herbal consumption on pregnancy and neonatal outcomes.

Methods: A retrospective observational study was conducted during the study period November 2010-September 2013. Six hundred and thirty expectant mothers were interviewed within three days after childbirth in a public Hospital in the South of Italy.

Results: Due to a lack of data, a total of six hundred interviews were considered. Four hundred and eighty six women (81%) reported to have constantly used at least one herbal product throughout the pregnancy period. The study enrolled mostly women between 31 and 40 years of age, with a middle-high level of education, married and employed. The most commonly used herbal products, taken by oral route and for the entire period of pregnancy, were chamomile, fennel, propolis, cranberry, lemon balm, ginger, valerian and mallow. The most relevant source of information for the majority of participants was the doctor (95%), and most of the women (72%) informed their doctors about their use of herbal remedies.

Conclusions: The regular chamomile consumption resulted in a higher risk of pre-term delivery, lower birth weight and lower length of the newborn. Also a regular use of fennel resulted in a shorter gestational age. Finally, ginger intake resulted in a shorter gestational age and in a smaller circumference of the newborn's skull.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2015.08.046DOI Listing
November 2015

Distinct roles of the endocannabinoids anandamide and 2-arachidonoylglycerol in social behavior and emotionality at different developmental ages in rats.

Eur Neuropsychopharmacol 2015 Aug 14;25(8):1362-74. Epub 2015 Apr 14.

Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy. Electronic address:

To date, our understanding of the relative contribution and potential overlapping roles of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in the regulation of brain function and behavior is still limited. To address this issue, we investigated the effects of systemic administration of JZL195, that simultaneously increases AEA and 2-AG signaling by inhibiting their hydrolysis, in the regulation of socio-emotional behavior in adolescent and adult rats. JZL195, administered at the dose of 0.01mg/kg, increased social play behavior, that is the most characteristic social activity displayed by adolescent rats, and increased social interaction in adult animals. At both ages, these behavioral effects were antagonized by the CB1 cannabinoid receptor antagonist SR141716A and were associated with increased brain levels of 2-AG, but not AEA. Conversely, at the dose of 1mg/kg, JZL195 decreased general social exploration in adolescent rats without affecting social play behavior, and induced anxiogenic-like effects in the elevated plus-maze test both in adolescent and adult animals. These effects, mediated by activation of CB1 cannabinoid receptors, were paralleled by simultaneous increase in AEA and 2-AG levels in adolescent rats, and by an increase of only 2-AG levels in adult animals. These findings provide the first evidence for a role of 2-AG in social behavior, highlight the different contributions of AEA and 2-AG in the modulation of emotionality at different developmental ages and suggest that pharmacological inhibition of AEA and 2-AG hydrolysis is a useful approach to investigate the role of these endocannabinoids in neurobehavioral processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2015.04.005DOI Listing
August 2015

Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training.

Proc Natl Acad Sci U S A 2014 Dec 8;111(51):18333-8. Epub 2014 Dec 8.

Department of Physiology and Pharmacology, Sapienza University of Rome, 00185 Rome, Italy;

Previous studies have provided extensive evidence that administration of cannabinoid drugs after training modulates the consolidation of memory for an aversive experience. The present experiments investigated whether the memory consolidation is regulated by endogenously released cannabinoids. The experiments first examined whether the endocannabinoids anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) are released by aversive training. Inhibitory avoidance training with higher footshock intensity produced increased levels of AEA in the amygdala, hippocampus, and medial prefrontal cortex (mPFC) shortly after training in comparison with levels assessed in rats trained with lower footshock intensity or unshocked controls exposed only to the training apparatus. In contrast, 2-AG levels were not significantly elevated. The additional finding that posttraining infusions of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which selectively increases AEA levels at active synapses, administered into the basolateral complex of the amygdala (BLA), hippocampus, or mPFC enhanced memory strongly suggests that the endogenously released AEA modulates memory consolidation. Moreover, in support of the view that this emotional training-associated increase in endocannabinoid neurotransmission, and its effects on memory enhancement, depends on the integrity of functional interactions between these different brain regions, we found that disruption of BLA activity blocked the training-induced increases in AEA levels as well as the memory enhancement produced by URB597 administered into the hippocampus or mPFC. Thus, the findings provide evidence that emotionally arousing training increases AEA levels within prefrontal-limbic circuits and strongly suggest that this cannabinoid activation regulates emotional arousal effects on memory consolidation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1420285111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4280626PMC
December 2014

Memantine prevents memory consolidation failure induced by soluble beta amyloid in rats.

Front Behav Neurosci 2014 19;8:332. Epub 2014 Sep 19.

Department of Experimental and Clinical Medicine, Faculty of Medicine, University of Foggia Foggia, Italy.

It has been well documented that β-amyloid (Aβ) peptide accumulation and aggregation in the brain plays a crucial role in the pathophysiology of Alzheimer's disease (AD). However, a new orientation of the amyloid cascade hypothesis has evidenced that soluble forms of the peptide (sAβ) are involved in Aβ-induced cognitive impairment and cause rapid disruption of the synaptic mechanisms underlying memory. The primary aim of this study was to elucidate the effects of sAβ, acutely injected intracerebrally (i.c.v., 4 μM), on the short term and long term memory of young adult male rats, by using the novel object recognition task. Glutamatergic receptors have been proposed as mediating the effect of Aβ on synaptic plasticity and memory. Thus, we also investigated the effects of sAβ on prefrontal cortex (PFC) glutamate release and the specific contribution of N-methyl-D-aspartate (NMDA) receptor modulation to the effects of sAβ administration on the cognitive parameters evaluated. We found that a single i.c.v. injection of sAβ 2 h before testing did not alter the ability of rats to differentiate between a familiar and a novel object, in a short term memory test, while it was able to negatively affect consolidation/retrieval of long term memory. Moreover, a significant increase of glutamate levels was found in PFC of rats treated with the peptide 2 h earlier. Interestingly, memory deficit induced by sAβ was reversed by a NMDA-receptor antagonist, memantine (5 mg/kg i.p), administered immediately after the familiarization trial (T1). On the contrary, memantine administered 30 min before T1 trial, was not able to rescue long term memory impairment. Taken together, our results suggest that an acute i.c.v. injection of sAβ peptide interferes with the consolidation/retrieval of long term memory. Moreover, such sAβ-induced effect indicates the involvement of glutamatergic system, proposing that NMDA receptor inhibition might prevent or lead to the recovery of early cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2014.00332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168698PMC
October 2014

Strain- and context-dependent effects of the anandamide hydrolysis inhibitor URB597 on social behavior in rats.

Eur Neuropsychopharmacol 2014 Aug 20;24(8):1337-48. Epub 2014 May 20.

Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Rome, Italy. Electronic address:

Genetic and environmental factors play an important role in the cannabinoid modulation of motivation and emotion. Therefore, the aim of the present study was to test whether anandamide modulation of social behavior is strain- and context-dependent. We tested the effects of the anandamide hydrolysis inhibitor URB597 on social behavior and 50-kHz ultrasonic vocalizations (USVs) in adolescent and adult Wistar and Sprague-Dawley rats tested in different emotionally arousing conditions (familiarity/unfamiliarity to the test cage, low/high light). Under all experimental conditions, adolescent and adult Sprague-Dawley rats displayed higher levels of social behavior and emitted more 50-kHz USVs than Wistar rats. URB597 enhanced social play behavior in adolescent Wistar rats under all experimental conditions. However, URB597 only increased social interaction in adult Wistar rats under unfamiliar/high light conditions. URB597 did not affect adolescent social play behavior and adult social interaction in Sprague-Dawley rats under any experimental condition. Moreover, URB597 increased the USVs emitted during social interaction by adolescent Wistar and adult Sprague-Dawley rats tested under familiar/high light and unfamiliar/high light, respectively. These results show that anandamide has distinct roles in adolescent and adult social behaviors. Anandamide modulation of adolescent social play behavior is strain- but not context-dependent. Conversely, anandamide modulation of adult social behavior and USV emission depends upon both strain and experimental context. Furthermore, these results confirm that profound behavioral differences exist between Wistar and Sprague-Dawley rats, which may explain the sometimes contradictory effects of cannabinoid drugs on emotionality in different strains of rodents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.euroneuro.2014.05.009DOI Listing
August 2014

An updated animal model capturing both the cognitive and emotional features of post-traumatic stress disorder (PTSD).

Front Behav Neurosci 2014 29;8:142. Epub 2014 Apr 29.

Department of Physiology and Pharmacology, Sapienza University of Rome Rome, Italy ; Sapienza School of Advanced Studies, Sapienza University of Rome Rome, Italy.

The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines post-traumatic stress disorder (PTSD) as a "trauma and stressor-related disorder". PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e., social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffering effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets of the pathology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2014.00142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010768PMC
May 2014

Chronic nandrolone administration induces dysfunction of the reward pathway in rats.

Steroids 2014 Jan;79:7-13

Data in animal models and surveys in humans have revealed psychiatric complications of long-term anabolic androgenic steroid abuse. However, the neurobiochemical mechanisms behind the observed behavioral changes are poorly understood. The aim of the present study was to investigate the effects of nandrolone decanoate on emotional behavior and neurochemical brain alterations in gonadally intact male rats. The behavioral reactivity to the elevated plus maze and the social interaction test was used to assess anxiety-related symptoms, and the sucrose preference test was used to evaluate anhedonia. Dopaminergic, serotonergic and noradrenergic transmissions were also evaluated in selected brain areas. The chronic administration of nandrolone, at 5 mg kg(-1) injected daily for 4 weeks, induced the loss of sweet taste preference, a sign of anhedonia and dysfunction of the reward pathway. The behavioral outcomes were accompanied by reductions in the dopamine, serotonin and noradrenaline contents in the nucleus accumbens. Alterations in the time spent in the open arms and in the social interaction test were not found, suggesting that nandrolone did not induce an anxiogenic profile. No differences were revealed between the experimental groups in the amygdala in terms of the neurotransmitters measured. Our data suggest that nandrolone-treated rats have a depressive, but not anxiogenic-like, profile, accompanied by brain region-dependent changes in dopaminergic, serotonergic and noradrenergic neurotransmission. As anabolic androgenic steroid dependence is plausibly the major form of worldwide substance dependence that remains largely unexplored, it should be highlighted that our data could contribute to a better understanding of the altered rewards induced by nandrolone treatment and to the development of appropriate treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2014

Social play behavior, ultrasonic vocalizations and their modulation by morphine and amphetamine in Wistar and Sprague-Dawley rats.

Psychopharmacology (Berl) 2014 Apr 13;231(8):1661-73. Epub 2013 Nov 13.

Department of Science, Section of Biomedical Sciences and Technologies, University "Roma Tre", Viale G. Marconi 446, 00146, Rome, Italy.

Rationale: Social play behavior is the most characteristic social behavior in young mammals. It is highly rewarding and crucial for proper neurobehavioral development. Despite the importance of genetic factors in normal and pathological social behaviors, little information is available about strain influences on social play.

Objective And Methods: The aim of this study was to investigate differences in social play behavior, 50-kHz ultrasonic vocalizations (USVs) and their modulation by acute morphine and amphetamine administration in two rat strains widely used in behavioral pharmacology studies, i.e., Wistar and Sprague-Dawley rats.

Results: Sprague-Dawley rats showed higher levels of social play than Wistar rats. In both strains, no correlation was found between the performance of social behaviors and the emission of 50-kHz USVs. In Wistar and Sprague-Dawley rats, morphine increased and amphetamine decreased social play. The effects of morphine, however, were more pronounced in Wistar than Sprague-Dawley animals. In both strains, morphine did not affect USV emission, while amphetamine increased it during cage exploration. In Sprague-Dawley rats only, amphetamine decreased USVs during social interaction.

Conclusions: Wistar and Sprague-Dawley rats differ in their absolute levels of social play behavior and 50-kHz USVs, and quantitative differences exist in their response to pharmacological manipulations of social play. The emission of 50-kHz USVs and the behavioral parameters thought to reflect rewarding social interactions in adolescent rats are dissociable.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00213-013-3337-9DOI Listing
April 2014

Hindbrain noradrenergic input to the hypothalamic PVN mediates the activation of oxytocinergic neurons induced by the satiety factor oleoylethanolamide.

Am J Physiol Endocrinol Metab 2013 Nov 24;305(10):E1266-73. Epub 2013 Sep 24.

Department of Physiology and Pharmacology "V. Erspamer", Sapienza University of Rome, Rome, Italy;

Oleoylethanolamide (OEA) is a gut-derived endogenous lipid that stimulates vagal fibers to induce satiety. Our previous work has shown that peripherally administered OEA activates c-fos transcription in the nucleus of the solitary tract (NST) and in the paraventricular nucleus (PVN), where it enhances oxytocin (OXY) expression. The anorexigenic action of OEA is prevented by the intracerebroventricular administration of a selective OXY receptor antagonist, suggesting a necessary role of OXYergic mediation of OEA's effect. The NST is the source of direct noradrenergic afferent input to hypothalamic OXY neurons, and therefore, we hypothesized that the activation of this pathway might mediate OEA effects on PVN neurons. To test this hypothesis, we subjected rats to intra-PVN administration of the toxin saporin (DSAP) conjugated to an antibody against dopamine-β-hydroxylase (DBH) to destroy hindbrain noradrenergic neurons. In these rats we evaluated the effects of OEA (10 mg/kg, ip) on feeding behavior, on c-Fos and OXY immunoreactivity in the PVN, and on OXY immunoreactivity in the posterior pituitary gland. We found that the DSAP lesion completely prevented OEA's effects on food intake, on Fos and OXY expression in the PVN, and on OXY immunoreactivity of the posterior pituitary gland; all effects were maintained in sham-operated rats. These results support the hypothesis that noradrenergic NST-PVN projections are involved in the activation of the hypothalamic OXY system, which mediates OEA's prosatiety action.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpendo.00411.2013DOI Listing
November 2013

The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons.

Peptides 2013 Nov 16;49:21-6. Epub 2013 Aug 16.

Department of Physiology and Pharmacology, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.

The anandamide monounsaturated analogue oleoylethanolamide (OEA) acts as satiety signal released from enterocytes upon the ingestion of dietary fats to prolong the interval to the next meal. This effect, which requires intact vagal fibers and intestinal PPAR-alpha receptors, is coupled to the increase of c-fos and oxytocin mRNA expression in neurons of the paraventricular nucleus (PVN) and is prevented by the intracerebroventricular administration of a selective oxytocin antagonist, thus suggesting a necessary role of oxytocinergic neurotransmission in the pro-satiety effect of OEA. By brain microdialysis and immunohistochemistry, in this study we demonstrate that OEA treatment can stimulate oxytocin neurosecretion from the PVN and enhance oxytocin expression at both axonal and somatodendritic levels of hypothalamic neurons. Such effects, which are maximum 2h after OEA administration, support the hypothesis that the satiety-inducing action of OEA is mediated by the activation of oxytocin hypothalamic neurons.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.peptides.2013.08.006DOI Listing
November 2013

Modulatory activity of soluble beta amyloid on HPA axis function in rats.

Curr Pharm Des 2014 ;20(15):2539-46

Dept. of Clinical and Experimental Medicine, Faculty of Medicine c/o OO.RR., University of Foggia, Viale L. Pinto 71100 Foggia, Italy.

Despite the consolidation of the amyloid hypothesis, the main component of senile plaques in Alzheimer's disease (AD), recent findings have led to a conceptual shift opening new questions about the potential physiological role of this peptide. In addition, soluble beta amyloid (sBA), in transgenic AD model, resulted to be increased after chronic and acute stress and alterations in cortisol levels have been reported in AD. Impaired hypothalamic pituitary adrenal (HPA) axis has been linked to depressive state and, consistently, we have previously demonstrated that BA is able to provoke depressive-like profile in rats. Here we further analysed the effect of the peptide in behavioural paradigms used to study emotional and cognitive response, by using the passive avoidance task, for cognitive parameters, and the sucrose preference test (SPT), to evaluate anhedonia. Moreover, in order to correlate behavioural with neurochemical and neuroendocrinal data, we investigated the effects of the peptide on noradrenergic system in amygdala (AMY), prefrontal cortex (PFC) and hippocampus (HIPP) along with plasmatic corticosterone and hypothalamic corticotrophin releasing factor (CRF). We found that BA-treated animals showed an impaired memory consolidation of inhibitory avoidance training, while no effect was evident in SPT. These results lead us to hypothesize a different response to stress coping behaviour in BA treated rats. Moreover, BA caused a significant increase in noradrenaline (NA) in PFC and HIPP, while in AMY was decreased. Consistently, we found a significant decrease in plasma corticosterone concentrations in BA-treated rats. Taken together, our data suggest that BA exerts an inhibitory effect on HPA axis activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/13816128113199990500DOI Listing
February 2015

Novelty-induced emotional arousal modulates cannabinoid effects on recognition memory and adrenocortical activity.

Neuropsychopharmacology 2013 Jun 22;38(7):1276-86. Epub 2013 Jan 22.

Department of Physiology and Pharmacology, Sapienza University of Rome, P.le A. Moro 5, Rome, Italy.

Although it is well established that cannabinoid drugs can influence cognitive performance, the findings-describing both enhancing and impairing effects-have been ambiguous. Here, we investigated the effects of posttraining systemic administration of the synthetic cannabinoid agonist WIN55,212-2 (0.1, 0.3, or 1.0 mg/kg) on short- and long-term retention of object recognition memory under two conditions that differed in their training-associated arousal level. In male Sprague-Dawley rats that were not previously habituated to the experimental context, WIN55,212-2 administered immediately after a 3-min training trial, biphasically impaired retention performance at a 1-h interval. In contrast, WIN55,212-2 enhanced 1-h retention of rats that had received extensive prior habituation to the experimental context. Interestingly, immediate posttraining administration of WIN55,212-2 to non-habituated rats, in doses that impaired 1-h retention, enhanced object recognition performance at a 24-h interval. Posttraining WIN55,212-2 administration to habituated rats did not significantly affect 24-h retention. In light of intimate interactions between cannabinoids and the hypothalamic-pituitary-adrenal axis, we further investigated whether cannabinoid administration might differently influence training-induced glucocorticoid activity in rats in these two habituation conditions. WIN55,212-2 administered after object recognition training elevated plasma corticosterone levels in non-habituated rats whereas it decreased corticosterone levels in habituated rats. Most importantly, following pretreatment with the corticosterone-synthesis inhibitor metyrapone, WIN55,212-2 effects on 1- and 24-h retention of non-habituated rats became similar to those seen in the low-aroused habituated animals, indicating that cannabinoid-induced regulation of adrenocortical activity contributes to the environmentally sensitive effects of systemically administered cannabinoids on short- and long-term retention of object recognition memory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/npp.2013.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656371PMC
June 2013

Neuroendocrine profile in a rat model of psychosocial stress: relation to oxidative stress.

Antioxid Redox Signal 2013 Apr;18(12):1385-99

Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.

Aims: Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine alterations in a rat model of chronic psychosocial stress, the social isolation.

Results: Significant elevations in the hypothalamic levels of corticotropin-releasing factor and plasmatic adrenocorticotropic hormone were observed from 4 weeks of social isolation. Increased levels of peripheral markers of the HPA-axis (plasmatic and salivary corticosterone) were observed at a later time point of social isolation (7 weeks). Alteration in the exploratory activity of isolated rats followed the same time course. Increased expression of markers of oxidative stress (8-hydroxy-2-deoxyguanosine [8OhdG] and nitrotyrosine) and NOX2 mRNA was early detectable in the hypothalamus of isolated rats (after 2 weeks), but later (after 7 weeks) in the adrenal gland. A 3-week treatment with the antioxidant/NOX inhibitor apocynin stopped the progression of isolation-induced alterations of the HPA-axis. Rats with a loss-of-function mutation in the NOX2 subunit p47(phox) were totally protected from the alterations of the neuroendocrine profile, behavior, and increased NOX2 mRNA expression induced by social isolation.

Innovation: We demonstrate that psychosocial stress induces early elevation of NOX2-derived oxidative stress in the hypothalamus and consequent alterations of the HPA-axis, leading ultimately to an altered behavior.

Conclusion: Pharmacological targeting of NOX2 might be of crucial importance for the treatment of psychosocial stress-induced psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/ars.2012.4569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3603501PMC
April 2013

Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats.

J Neurosci 2012 Oct;32(43):14899-908

Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, 3584 CG Utrecht, The Netherlands.

The brain endocannabinoid system plays a crucial role in emotional processes. We have previously identified an important role for endocannabinoids in social play behavior, a highly rewarding form of social interaction in adolescent rats. Here, we tested the hypothesis that endocannabinoid modulation of social play behavior occurs in brain regions implicated in emotion and motivation. Social play increased levels of the endocannabinoid anandamide in the amygdala and nucleus accumbens (NAc), but not in prefrontal cortex or hippocampus of 4- to 5-week-old male Wistar rats. Furthermore, social play increased phosphorylation of CB1 cannabinoid receptors in the amygdala. Systemic administration of the anandamide hydrolysis inhibitor URB597 increased social play behavior, and augmented the associated elevation in anandamide levels in the amygdala, but not the NAc. Infusion of URB597 into the basolateral amygdala (BLA) increased social play behavior, and blockade of BLA CB1 cannabinoid receptors with the antagonist/inverse agonist SR141716A prevented the play-enhancing effects of systemic administration of URB597. Infusion of URB597 into the NAc also increased social play, but blockade of NAc CB1 cannabinoid receptors did not antagonize the play-enhancing effects of systemic URB597 treatment. Last, SR141716A did not affect social play after infusion into the core and shell subregions of the NAc, while it reduced social play when infused into the BLA. These data show that increased anandamide signaling in the amygdala and NAc augments social play, and identify the BLA as a prominent site of action for endocannabinoids to modulate the rewarding properties of social interactions in adolescent rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.0114-12.2012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3496852PMC
October 2012

Neurochemical differences in two rat strains exposed to social isolation rearing.

Acta Neuropsychiatr 2012 Oct;24(5):286-95

Department of Human Physiology and Pharmacology, Vittorio Erspamer, University of Rome "La Sapienza", Rome, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1601-5215.2011.00627.xDOI Listing
October 2012