Publications by authors named "Ehsan Saboory"

55 Publications

The protective effect of zinc on morphine-induced testicular toxicity via p53 and Akt pathways: An in vitro and in vivo approach.

J Trace Elem Med Biol 2021 Sep 8;67:126776. Epub 2021 May 8.

Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

Background: Chronic use of morphine is associated with reproductive complications, such as hypogonadism and infertility. While the side effects of morphine have been extensively studied in the testis, much less is known regarding the effects of morphine on Sertoli cells and the effects of zinc on morphine-induced testicular injury as well as their underlying mechanisms. Therefore, the purpose of this study was to investigate the effect of morphine (alone and co-administered with zinc) on cell viability and apoptosis of the testicular (Sertoli) cells as well as the tumor suppressor p53 and phosphorylated-protein kinase B (p-Akt) protein levels in both in vitro and in vivo models.

Methods: Cultured Sertoli cells were exposed to morphine (23 μM), zinc (8 μM), and zinc prior to morphine and their effects on Sertoli cell viability and apoptosis were investigated. Morphine (3 mg/kg) and zinc (5 mg/kg, 1 h before morphine) were also injected intraperitoneally to rats and then the apoptotic changes in the testis were evaluated.

Results: Cell viability and p-Akt protein levels decreased in morphine-treated cells, while apoptosis and p53 protein expression increased in these cells. Pretreatment with zinc recovered morphine-induced apoptotic effects, as well as over-expression of p53 and down-regulation of p-Akt. These findings were supported by a subsequent animal study.

Conclusion: The present data indicated the protective effect of zinc against morphine-induced testicular (Sertoli) cell toxicity via p53/Akt pathways in both in vivo and in vitro models and suggested the clinical importance of zinc on infertility among chronic opioid users and addicted men.
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http://dx.doi.org/10.1016/j.jtemb.2021.126776DOI Listing
September 2021

Crocetin suppresses the growth and migration in HCT-116 human colorectal cancer cells by activating the p-38 MAPK signaling pathway.

Res Pharm Sci 2020 Dec 27;15(6):592-601. Epub 2020 Nov 27.

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, I.R. Iran.

Background And Purpose: Crocetin is a natural antioxidant that is found in the crocus flower and (fruit). Previous studies have reported its anticancer activity both and . In addition, crocetin suppresses the growth and migration of human colorectal cancer cells, however, its mechanism of action remains to be elucidated. Therefore, the present study investigated the molecular mechanism of crocetin effect on colorectal cancer cells (HCT-116) .

Experimental Approach: HCT-116 cells were treated with different concentrations (0, 200, 400, 600, and 800 μM) of crocetin for 24 h. The cell survival rate was measured by MTT assay. Cell migration capacity was evaluated using the wound healing assay. The expression levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP-9) was monitored by RT-PCR. Phosphorylation of focal adhesion kinase (FAK) and p38 mitogen-activated protein kinase (MAPK) was determined using western blot.

Findings/results: The proliferation of HCT-116 was inhibited by crocetin at 800 μM ( < 0.001). Crocetin prevented migration of HCT-116 cells ( < 0.05) and suppressed VEGF and MMP-9 mRNA expression ( < 0.001) and increased phosphorylation of p38 (MAPK; < 0.001). However, no significant change in the phosphorylation of FAK was observed.

Conclusion And Implication: These data suggested that crocetin-induced growth- and migration- suppressing effects on HCT-116 cells may partially depend on the regulation of the p38 (MAPK) signaling pathway.
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http://dx.doi.org/10.4103/1735-5362.301344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020854PMC
December 2020

Effect of orally-administrated thymoquinone during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring.

Iran J Basic Med Sci 2021 Jan;24(1):30-37

Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Objectives: This study aimed to assess the impact of orally-administrated thymoquinone (TQ) during pregnancy on litter size, pentylenetetrazol-induced seizure, and body weight in rat offspring.

Materials And Methods: In this experimental study, 64 pregnant rats were divided into groups according to the doses of TQ (0,10, 40, and 80 mg/kg) and gestational week (GW2 and GW3) of TQ administration. After parturition, the pups were counted, weighed, and assessed for pentylenetetrazol (PTZ)-induced seizure on postnatal days 14 (P14) and 21 (P21).

Results: In GW2 treated rats, TQ 40 mg/kg decreased seizure stages compared with control only on P14 while seizure duration significantly decreased on P14 and P21. On P14, 40 mg/kg TQ increased latency to the first seizure but decreased it on P21. In addition, 40 mg/kg dose decreased body weight (BW) on P1, P14, and P21 compared with 10 mg/kg dose and control groups. The dose of 80 mg/kg led to a complete pregnancy loss. In GW3 treated rats, only 10 mg/kg TQ decreased the seizure stages on P14 and P21. None of the doses had a significant effect on seizure duration and latency. TQ 40 and 80 mg/kg led to a low birth weight while increased BW on P14 and P21. A 50% decrease in litter size was observed in 80 mg/kg treated rats.

Conclusion: Prenatal TQ may have anticonvulsant effects. The effects of TQ on BW of offspring depend on its dose and administration time. Also, a high dose of TQ at GW2 can be severely toxic for pregnancy.
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http://dx.doi.org/10.22038/ijbms.2020.47479.10930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894635PMC
January 2021

Neurological manifestations of coronavirus infections: role of angiotensin-converting enzyme 2 in COVID-19.

Int J Neurosci 2021 Jan 14:1-8. Epub 2021 Jan 14.

Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Aim Of The Study: In December 2019, a highly pathogenic coronavirus called SARS-CoV-2 (formerly identified as 2019-nCoV) appeared in Wuhan, China, and has since been spreading rapidly around the world. we reviewed the neurological manifestations of this infection and the potential of ACE2 in the nervous system.

Materials And Methods: Six databases (Medline, Scopus, Embase, Web of Science, WHO, and google scholar) were searched and screened by the authors for having appropriate information about covid-19. Finally, 72 studies were identified, summarized and reviewed.

Result: The most specific manifestation of SARS-CoV-2 patients is pulmonary distress, and several patients admitted to intensive care units were not able to breathe spontaneously. In addition, the SARS-CoV-2 outbreak has a significant effect on nervous systems and may even lead to serious neurological damage. The neuroinvasive pathobiology is still not fully elucidated and thus the effect of CoV infections on the nervous system needs to be explored. The spike protein of the virus and the angiotensin-converting enzyme 2 (ACE2) lead to the presence of both SARS-CoV and SARS-CoV-2 in the cells and, subsequently, decreased ACE2 expression.

Conclusion: The therapeutic possibilities of ACE2 antibody, ACE2-derived peptides, and small molecule blockers of ACE2 include a receptor-binding domain blocking approach. Hence, future studies of ACE2 may be very helpful in discovering a therapy for SARS-CoV-2.
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http://dx.doi.org/10.1080/00207454.2020.1849193DOI Listing
January 2021

Effects of treadmill exercise and sex hormones on learning, memory and hippocampal brain-derived neurotrophic factor levels in transient congenital hypothyroid rats.

Behav Pharmacol 2020 10;31(7):641-651

Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.

Transient thyroid function abnormalities at birth exhibit intellectual developmental and cognitive disorders in adulthood. Given the well-known effects of physical activity and sex hormones on cognitive functions and brain-derived neurotrophic factor (BDNF), the present study examined the effects of treadmill exercise, sex hormones, and the combined treatment on learning and memory and hippocampal BDNF levels in transient congenital hypothyroid rats. To induce hypothyroidism, 6-propyl-2-thiouracil was added to the drinking water from the 6th day of gestation to the 21st postnatal day (PND). From PNDs 28 to 47, female and male pup rats received 17β-estradiol and testosterone, respectively, and about 30 min later, they were forced to run on the treadmill for 30 min once a day. On PNDs 48-55, spatial learning and memory of all rats tested in the water maze, which followed by measurement of BDNF in the hippocampus. Results showed that developmental hypothyroidism induced significant deficits in spatial learning and memory and hippocampal BDNF in both male and female rats. In both male and female hypothyroid rats, exercise and exercise plus sex hormones, but not sex hormones alone alleviated learning and memory deficits and all treatments (exercise, sex hormones, and the combined treatment) increased hippocampal BDNF. These disconnects in the effects of exercise, sex hormones and the combined treatment on behavioral and neurochemical outcomes suggest that a neurochemical mechanism other than hippocampal BDNF might contribute in the ameliorating effects of exercise on learning and memory deficits induced by developmental thyroid hormone insufficiency.
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http://dx.doi.org/10.1097/FBP.0000000000000572DOI Listing
October 2020

The Novel Insight of SARS-CoV-2 Molecular Biology and Pathogenesis and Therapeutic Options.

DNA Cell Biol 2020 Oct 21;39(10):1741-1753. Epub 2020 Jul 21.

Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

On December 31, 2019, a novel coronavirus, being the third highly infective CoV and named as coronavirus disease 2019 (COVID-19) in the city of Wuhan, was announced by the World Health Organization. COVID-19 has a 2% mortality rate, is known as the third extremely infective CoV infection, and has a mortality rate less than MERS-CoV and SARS-CoV. The CoV family comprises a chief number of positive single-stranded (+) RNA viruses that are recognized in mammals. The 2019-nCoV patients showed that the angiotensinconverting enzyme (ACE2) was the same for SARS-CoV. Structural proteins have an essential role in virus released and budding to various host cells. Notably, evidence indicated human-to-human transmission, along with several exported patients of virus infection worldwide. Nowadays, no licensed antivirals drugs or vaccines for being utilized against these coronavirus infections are recognized. There is an urgent requirement for an extensive research of CoV infections to disclose the route of extension, pathogenesis, and diagnosis and then to recognize the therapeutic targets to facilitate disease control and surveillance. In this article, we present an overview of the common biological criteria of CoVs and explain pathogenesis with a focus on the therapeutic approach to suggest potential goals for treating and monitoring this emerging zoonotic disease.
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http://dx.doi.org/10.1089/dna.2020.5703DOI Listing
October 2020

Prenatal stress increased γ2 GABAA receptor subunit gene expression in hippocampus and potentiated pentylenetetrazol-induced seizure in rats.

Iran J Basic Med Sci 2020 Jun;23(6):724-729

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran.

Objectives: Stress during pregnancy is able to bring extensive effects on neurobehavioral development in offspring. The GABAergic system plays a pivotal role in neuronal excitability, which can be affected by prenatal stress (PS). This study aimed to evaluate impact of the PS on γ2 subunit of gamma-aminobutyric acid A (GABAA) receptor gene expression in the hippocampus and seizure induced by pentylenetetrazol (PTZ) in developing rats.

Materials And Methods: In this experimental study, female Wistar rats were exposed to restraint stress during gestation and their offspring were studied on postnatal days 14 and 21 (P14 and P21, respectively) for epileptic behaviors and γ2 GABAA receptor subunit gene expression. Quantitative real-time PCR was used for evaluating the γ2 GABAA receptor subunit gene expression in rat pups. Meanwhile, PTZ was injected into the pups, and seizure behaviors were recorded for 60 min.

Results: The results showed that γ2 subunit mRNA expression significantly increased in the hippocampus of the stressed pups. The expression level of γ2 subunit was higher on P21 compared to that on P14 in both groups. Number of seizures with tonic-clonic features increased in pups of stressed group compared to the control group. Prenatal stress significantly caused an increase in the total score of seizure on P21.

Conclusion: The effect of PS on seizure susceptibility is age-specific; the increased γ2 subunit level in the hippocampus might be, at least in part, the underlying mechanism for PS-induced augmentation of seizures in immature rats.
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http://dx.doi.org/10.22038/ijbms.2020.39519.9371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351438PMC
June 2020

The impact of sleep deprivation on sexual behaviors and FAAH expression in the prefrontal cortex of male rats.

Neurosci Lett 2020 09 16;735:135254. Epub 2020 Jul 16.

Research Center of Psychiatry and Behavioral Sciences, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Sleep deprivation (SD) causes alterations in the function of the endocannabinoid (EC) system and also results in alteration in many behaviors such as increased anxiety, deteriorated alertness, memory deficits, as well as sexual behaviors. Controversial data about the effects of SD on sexual response are provided. Fatty acid amide hydrolase (FAAH), the enzymes involved in the degradation of the EC system play an important role in the function of the EC system. This study aimed to investigate the effect of REM SD (RSD) and total SD (TSD) on the sexual behaviors and FAAH expression in the prefrontal cortex (PFC) of male rats. RSD was carried out through the flower pot technique for 24 h and 48 h, and TSD also was induced by keeping awake the rats by gentle handling for 6 h. Immediately after RSD and TSD, sexual behaviors were recorded for 45 min. Sexual behaviors were reduced by both types of RSD and TSD. The deleterious effects of 24 h RSD were more severe compared with 6 h of TSD. Serum testosterone concentration was significantly higher after TSD but not RSD compared to the normal sleep (NS) group. FAAH expression in the PFC was significantly reduced after both RSD and TSD compared to the NS group. Given that the function of the EC system has been previously shown to change different behaviors such as sexual activity, our results could suggest that behavioral effects of both types of SD on sexual behavior may partially result from activation of this signaling pathway by the reduction of FAAH in the PFC.
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http://dx.doi.org/10.1016/j.neulet.2020.135254DOI Listing
September 2020

Norepinephrine, neurodevelopment and behavior.

Neurochem Int 2020 05 21;135:104706. Epub 2020 Feb 21.

Neurophysiology Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

Neurotransmitters play critical roles in the developing nervous system. Among the neurotransmitters, norepinephrine (NE) is in particular postulated to be an important regulator of brain development. NE is expressed during early stages of development and is known to regulate both the development of noradrenergic neurons and the development of target areas. NE participates in the shaping and the wiring of the nervous system during the critical periods of development, and perturbations in this process can alter the brain's developmental trajectory, which in turn can cause long-lasting and even permanent changes in the brain function and behavior later in life. Here we will briefly review evidence for the role of noradrenergic system in neurodevelopmental processes and will discuss about the potential disruptors of noradrenergic system during development and their behavioral consequences.
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http://dx.doi.org/10.1016/j.neuint.2020.104706DOI Listing
May 2020

Exercise and insulin-like growth factor 1 supplementation improve angiogenesis and angiogenic cytokines in a rat model of diabetes-induced neuropathy.

Exp Physiol 2020 05 21;105(5):783-792. Epub 2020 Apr 21.

Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

New Findings: What is the central question of this study? Do changes in levels of angiogenesis-related mediators [vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and nuclear factor-κB (NF-κB)] in the sciatic nerve mediate diabetic neuropathy in the streptozotocin-induced type 1 diabetic male rat? Can exercise and insulin-like growth factor 1 (IGF-I) treatment improve the diabetes-related decrease in angiogenesis in sciatic nerve in these animals? What is the main finding and its importance? Levels of VEGF-A, TSP-1 and NF-κB change in the sciatic nerve of diabetic rats and might mediate diabetic neuropathy. Treatment with IGF-I and exercise could increase angiogenesis in the diabetic rats by increasing VEGF-A and decreasing TSP-1 and NF-κB expression in the sciatic nerve.

Abstract: Diabetic neuropathy is a severe complication of diabetes that affects 40-50% of diabetic people in the world. The aim of this study was to characterize alterations in angiogenesis and related molecular mediators in the sciatic nerve in diabetic conditions alone or in diabetes in combination with exercise and/or administration of insulin-like growth factor 1 (IGF-I). Forty male Wistar rats were assigned into one of five groups, namely control, diabetes, diabetes + exercise, diabetes + IGF-I and diabetes + exercise + IGF-I. Type 1 diabetes was induced by i.p. injection of streptozotocin (60 mg kg ). After 30 days of treatment with exercise or IGF-I alone or in combination, diabetic neuropathy was evaluated with a hotplate, glycated haemoglobin was measured, angiogenesis was determined by immunostaining for PECAM-1/CD31, and expressions of vascular endothelial growth factor-A (VEGF-A), thrombospondin-1 (TSP-1) and nuclear factor-κB (NF-κB) were determined by enzyme-linked immunosorbent assay.After 4 weeks, the diabetes group showed a significant decrease in capillary density and VEGF-A levels, but a significant increase in glycated haemoglobin in blood, TSP-1 and NF-κB levels in the sciatic nerve compared with the control group, and these effects were ameliorated by exercise and IGF-I. However, simultaneous treatment of diabetic rats with IGF-I and exercise did not have any synergistic effects. These findings indicate that diabetes-induced neuropathy may be associated, in part, with decreased angiogenesis mediated by overproduction of TSP-1 and NF-κB, in addition to reduced production of VEGF-A. The findings also showed that exercise and IGF-I can reduce neuropathy, followed by increased angiogenesis, by changes in TSP-1, NF-κB and VEGF-A production levels.
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http://dx.doi.org/10.1113/EP088069DOI Listing
May 2020

Involvement of endocannabinoid system, inflammation and apoptosis in diabetes induced liver injury: Role of 5-HT3 receptor antagonist.

Int Immunopharmacol 2020 Feb 8;79:106158. Epub 2020 Jan 8.

Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Iran; Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

Confident relationships between diabetes andliver damagehave previously been established. This study was designed to evaluate hepaticinflammation, apoptosis, and endocannabinoid system alterations in diabetes with or withouttropisetrontreatment. Rats were assigned to five equal groups: control, tropisetron, diabetes, tropisetron+diabetes, and glibenclamide+diabetes (n = 7 in each group). Rats were treated with tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) as a positive control for two weeks after type 1 diabetes induction.Inflammatory cytokines tumor necrosis factor-alpha and interleukin 6 (TNF-α and IL-6) levels, apoptotic cells, and fatty acid amide hydrolase (FAAH) enzyme, at both transcriptional and protein levels increased, while the gene expression of cannabinoid receptor 1 (CB1) and its protein level decreased in the diabetic liver compared to the control. Treatment with tropisetron reversed TNF-α, apoptotic index, and endocannabinoid system components. These effects were equipotent with glibenclamide, indicating that tropisetroncan protect liver tissue against diabetic disturbances. These findings strongly support the idea that diabetes-induced liver abnormality is mediated by inflammatory reactions, apoptosis, and endocannabinoid system, and that these effects can be alleviated by using tropisetron as an antioxidant and anti-inflammatory agent.
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http://dx.doi.org/10.1016/j.intimp.2019.106158DOI Listing
February 2020

Long-time effects of prenatal morphine, tramadol, methadone, and buprenorphine exposure on seizure and anxiety in immature rats.

Int J Neurosci 2020 Sep 6;130(9):898-905. Epub 2020 Jan 6.

Faculty of Pharmacy, Department of Pharmaceutics, Tehran University of Medical Sciences, Tehran, Iran.

This study aimed to investigate seizures and anxiety-like behaviors in immature rats prenatally exposed to opiate drugs. Pregnant rats were randomly divided into five groups: saline, morphine, tramadol, methadone, and buprenorphine. Administrations were performed intraperitoneally once a day for the last seven days of pregnancy. Neonatal rats were subdivided into ten groups, split according to sex. Anxiety-like behavior was tested on postnatal day (PD) 19. On PD 20, seizure was induced by PTZ injection. Morphine in male rats had an increased time to onset ( < 0.005), whereas there was a decreased number of tonic-clonic seizures in females ( < 0.05). Tramadol had an increased duration of tonic-clonic seizures compared to morphine and methadone in males  < 0.005 Moreover, tramadol decreased open arm time and locomotor activity in males more than in females ( < 0.05). Methadone decreased open arm time in males ( < 0.05). Furthermore, buprenorphine and tramadol decreased open arm entrance in male rats ( < 0.05). It was demonstrated that prenatal tramadol significantly increases both the duration of seizures and anxiety-like behaviors in immature male rats, whereas morphine decreases both of them. The effects of tramadol on seizure and anxiety-like behavior may be due to the comorbid occurrence of the symptoms of these two disorders.
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http://dx.doi.org/10.1080/00207454.2019.1709841DOI Listing
September 2020

Crocetin promotes angiogenesis in human endothelial cells through PI3K-Akt-eNOS signaling pathway.

EXCLI J 2019 21;18:936-949. Epub 2019 Oct 21.

Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Previous studies proved the pro-angiogenic effect of Crocetin, a natural carotenoid dicarboxylic acid, in both and models. However, the exact mechanism of Crocetin action has not completely been elucidated yet. The current experiment was designed to find the activity of PI3K-Akt-eNOS axis after the treatment of endothelial cells with Crocetin . Human Umbilical Vein Endothelial Cells (HUVECs) were incubated with various concentrations of Crocetin (1, 5, 25, 50, and 100 µM) over a period of 72 h. Crocetin significantly increased HUVECs viability after 72 h as compared with the control group. We also found that Crocetin promoted the formation of the capillary-like structure compared to the control (<0.05). Moreover, an improved migration rate and increased MMP-9 activity were observed in HUVECs that received 50 µM Crocetin (<0.05). Crocetin enhanced the uptake of Ac-LDL which is correlated with increased lipid metabolism. Based on the data from the current experiment, protein level of VEGFR-1, -2 and p-Akt/Akt, p-eNOS/eNOS ratios were increased 72 h after the treatment of HUVECs with Crocetin (<0.05). In contrast, the transcription level of VEGF was reduced in Crocetin-treated cells. These data demonstrated that Crocetin promotes HUVECs angiogenesis potential by the modulation of VEGF signaling pathway and increased cell viability. The PI3K/Akt/eNOS axis is required for a Crocetin-associated activity in endothelial cells.
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http://dx.doi.org/10.17179/excli2019-1175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868919PMC
October 2019

The modulatory effects of exercise on the inflammatory and apoptotic markers in rats with 1,2-dimethylhydrazine-induced colorectal cancer.

Can J Physiol Pharmacol 2020 Mar 15;98(3):147-155. Epub 2019 Oct 15.

Solid Tumor Research Center, Urmia University of Medical Sciences, Urmia, Iran.

This study aimed to investigate the underlying mechanisms in anti-tumorigenesis effects of exercise through evaluation of inflammation and apoptosis. Twenty-four Wistar rats were divided into control, exercise, 1,2-dimethylhydrazine (DMH), and DMH + exercise. After a week, rats in the DMH group were given DMH twice a week for 2 weeks. Animals in the exercise groups performed exercise on a treadmill 5 days/week for 8 weeks. After 8 weeks of training, levels of COX-2, PCNA, Bax, Bcl-2, and procaspase-3/cleaved caspase-3 were assessed. Histological changes, number of aberrant crypt foci (ACF), and serum levels of TNF-α and IL-6 were also analyzed. ACF number was significantly decreased following the exercise program. Protein levels of COX-2 and PCNA and serum levels of IL-6 and TNF-α were significantly elevated in the rats receiving DMH and downregulated after performing the exercise program ( < 0.05). Exercise upregulated apoptosis, which was evident from the increased Bax/Bcl2 ratio, and enhanced the expression levels of activated caspase-3 as compared to the DMH group. The colonic architecture was improved in DMH + exercise. Exercise can effectively attenuate DMH-induced increase of inflammatory markers. Exercise induces apoptosis at the downstream of the inflammatory response. Therefore, exercise may play a role as a moderator of inflammation to exert protective effects against colon cancer.
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http://dx.doi.org/10.1139/cjpp-2019-0329DOI Listing
March 2020

The relationship between stress during pregnancy with leptin and cortisol blood concentrations and complications of pregnancy in the mother

J Turk Ger Gynecol Assoc 2019 11 12;20(4):218-223. Epub 2019 Jul 12.

Islamic Azad University Faculty of Nursing and Midwifery Bonab, Miandoab, Iran

Objective: Pregnancy is one of the most stressful periods a woman experiences in her life. The present study was an attempt to determine the relationship between maternal stress during pregnancy and cortisol plus maternal serum leptin concentrations as well as pregnancy outcomes.

Material And Methods: This longitudinal study was conducted on 90 pregnant women in Miandoab city between 2015 and 2016. The samples were chosen from mothers with a gestational age of 24 to 28 weeks. The participants were asked to complete Cohen’s Perceived Stress Scale (PSS) and a demographic questionnaire and blood samples were taken from them. The mothers were then tracked with four-week intervals until the time of delivery and were asked to complete Cohen’s PSS each time along with a questionnaire related to maternal outcomes. Again, a blood sample was taken at the time of delivery. Data analysis was performed using SPSS 16. Descriptive statistics, Pearson’s correlation coefficient, and the t-test were employed for analysis.

Results: A significant relationship was found between maternal stress and preeclampsia (p=0.008). The relationships between preterm childbirth and maternal cortisol concentrations in weeks 24-28 (p=0.015), and between preterm childbirth and maternal leptin concentrations at the time of delivery (p=0.007) were also found to be significant.

Conclusion: Pregnancy and labor, as physically and mentally stressful events, can affect women’s physiologic and psychological indicators. As a consequence, during pregnancy, the cortisol and leptin index changes in response to the activity of the hypothalamic-pituitary axis and autonomic nervous system under stress.
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http://dx.doi.org/10.4274/jtgga.galenos.2019.2019.0010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883754PMC
November 2019

Prenatal stress and elevated seizure susceptibility: Molecular inheritable changes.

Epilepsy Behav 2019 07 24;96:122-131. Epub 2019 May 24.

Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.

Stressful episodes are common during early-life and may have a wide range of negative effects on both physical and mental status of the offspring. In addition to various neurobehavioral complications induced by prenatal stress (PS), seizure is a common complication with no fully explained cause. In this study, the association between PS and seizure susceptibility was reviewed focusing on sex differences and various underlying mechanisms. The role of drugs in the initiation of seizure and the effects of PS on the nervous system that prone the brain for seizure, especially the hypothalamic-pituitary-adrenal (HPA) axis, are also discussed in detail by reviewing the papers studying the effect of PS on glutamatergic, gamma-aminobutyric acid (GABA)ergic, and adrenergic systems in the context of seizure and epilepsy. Finally, epigenetic changes in epilepsy are described, and the underlying mechanisms of this change are expanded. As the effects of PS may be life-lasting, it is possible to prevent future psychiatric and behavioral disorders including epilepsy by preventing avoidable PS risk factors.
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http://dx.doi.org/10.1016/j.yebeh.2019.04.046DOI Listing
July 2019

Parental pre-conception stress status and risk for anxiety in rat offspring: specific and sex-dependent maternal and paternal effects.

Stress 2019 09 26;22(5):619-631. Epub 2019 May 26.

a Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences , Urmia , Iran.

Prenatal stressful events have long-lasting consequences on behavioral responses of offspring. While the effects of gestational and maternal stress have been extensively studied on psychological alterations in the progeny, little is known about effects of each parent's pre-conception life events on emotional responses in offspring. Here, the effect of maternal and/or paternal pre-conception stress was investigated on anxiogenic responses of offspring. Male and female adult rats were subjected to predatory stress (contactless exposure to a cat for 1 + 1 h per day) for 50 (male, : 12) and 15 (female, : 24) consecutive days; controls were not exposed. After the stress procedure, the control and stressed rats were mated to create four types of breeding pairs: control female/control male, stressed female/control male, control female/stressed male, and stressed female/stressed male. On postnatal days 30-31, the offspring were tested on the elevated plus maze and plasma corticosterone concentration was measured. Half of the pups were exposed to acute predatory stress before the elevated plus maze test. In most subgroups, corticosterone and anxiety-like behaviors in the offspring with both or only one parent exposed to pre-gestational stress increased compared to their control counterparts. However, under acute stress conditions, a different sex-dependent pattern of anxiety responses emerged. The combined effects of maternal and paternal stress were not additive. Hence, individual offspring behaviors can be influenced by the former life stress experiences of either parent. Incorporation of genetic and epigenetic aspects in development of neurobehavioral abnormalities and reprograming of the hypothalamic-pituitary-adrenal axis may contribute to this phenomenon. Early life stress (including during pregnancy) is known to have long-lasting effects on offspring, including emotional behaviors. Whether individual anxiety behaviors can be influenced by stress experiences of each parent even before a pregnancy is less well-understood. Our findings from this study on rats exposed to predator stress before mating suggest that maternal or paternal adult life events prior to pregnancy can lead to maladaptive behavior in their offspring later in life.
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http://dx.doi.org/10.1080/10253890.2019.1619075DOI Listing
September 2019

Interactive Effects of Exercise, Sex Hormones, and Transient Congenital Hypothyroidism on Long-Term Potentiation in Hippocampal Slices of Rat Offspring.

Basic Clin Neurosci 2019 Mar-Apr;10(2):119-135. Epub 2019 Mar 1.

Nervous System Stem Cells Research Center, Semnan University of Medical Sciences, Semnan, Iran.

Introduction: The long-term adverse effects of transient thyroid function abnormalities at birth on intellectual development are proven. The effect of exercise increases in the presence of sex hormones. The current study aimed at investigating the possibility that a combination of sex hormones and exercise has synergistic effects on neural plasticity in Transient Congenital Hypothyroidism (TCH) rats.

Methods: To induce hypothyroidism in the mothers, Propylthiouracil (PTU) was added to drinking water (100 mg/L) on the 6th day of gestation and continued until the 21 Postnatal Day. From Postnatal Day (PND) 28 to 47, the female and male pups received 17β-estradiol and testosterone, respectively. The mild treadmill exercise began 30 minutes after the sex hormones or vehicle administration. On PND 48, electrophysiological experiments were performed on brain slices.

Results: Increase of Long-Term Potentiation (LTP) was observed in sedentary-non-hormone female rats of TCH group, compared with that of the control. The exercise enhanced LTP in control rats, but the hormones showed no significant effect. The effect of exercise and sex hormone was not significant in the TCH group. The combination of exercise and testosterone enhanced LTP in TCH male rats, while the combination of exercise and estradiol or each of them individually did not produce such an effect on LTP in TCH female rats.

Conclusion: The study findings showed an increase in excitatory transmission despite the returning of thyroid hormone levels to normal range in TCH female rats. Also a combination treatment including exercise and testosterone enhanced LTP in male rats of TCH group, which was a gender-specific event.
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http://dx.doi.org/10.32598/bcn.9.10.170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484195PMC
March 2019

Acute and chronic effects of morphine on Low-Mg ACSF-induced epileptiform activity during infancy in mice hippocampal slices.

Res Pharm Sci 2019 Feb;14(1):46-54

Department of Pharmacology, Faculty of Veterinary Medicine, University of Tehran, Tehran, I.R. Iran.

Interaction of morphine and seizure is complex. Mouse brain hippocampal slices were used to estimate how acute and chronic morphine treatment alters the low-magnesium artificial cerebrospinal fluid (LM-ACSF)-induced seizure activity. Hippocampal slices were taken from the normal and morphine-treated mice. The normal mice received saline while the other group (morphine-treated mice) received morphine daily for 5 consecutive days. Saline/morphine administration was performed subcutaneously (s.c, 0.1 mL) at postnatal days 14-18. Hippocampal slices of all animals were perfused with LM-ACSF followed by different morphine concentrations (0, 10, 100, and 1000 μM) or naloxone (10 μM). Changes in the spike count were considered as indices for quantifying the seizure activity in the slices. In hippocampus of both groups perfused with 10 or 1000 μM morphine, epileptiform activity was suppressed while it was potentiated at 100 μM morphine. The excitatory effect of morphine at 100 μM was stronger in normal mice (acute exposure) than in dependent mice (chronic exposure). Naloxone suppressed the epileptiform activities in both groups. Suppressive effect of naloxone was more significant in morphine-treated mice than in normal mice. The seizure activity in morphine-dependent mice was more labile than that of normal mice. It can be concluded that morphine had a biphasic effect on LM-ACSF-induced epileptiform activities in both groups. The occurrence of seizure was comparable in acute and chronic exposure of morphine but strength of the effect was considerably robust in normal mice. The down regulation of opioid receptors in chronic exposure is likely to be responsible for these differences.
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http://dx.doi.org/10.4103/1735-5362.251852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407340PMC
February 2019

Curcumin modulates the angiogenic potential of human endothelial cells via FAK/P-38 MAPK signaling pathway.

Gene 2019 Mar 23;688:7-12. Epub 2018 Nov 23.

Neurophysiology Research Center, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Many phyto-compounds are found to have anti-angiogenesis property. Curcumin, a natural polyphenol, has been used as medicinal plant for years with different biological activities. Here, we investigated the effect of curcumin on angiogenesis potential of human endothelial cells. Human Umbilical Vein Endothelial Cells (HUVECs) were treated with different concentration of curcumin over a period of 72 h. Cell survival rate was measured by MTT assay. Cell migration and tubulogenesis were studied by scratch and tubulogenesis assays. The expression level of VEGF was monitored by RT-PCR. We also monitored the phosphorylation of FAK and P-38 MAPK by western blotting. Compared to control group, curcumin decreased HUVECs survival rate after 72 h. We found that the migration of HUVECs was decreased after curcumin treatment compared to the control (p < 0.0001). Cell alignment and tubulogenesis activity were found to be inhibited compared to cells from the VEGF group (p < 0.05). The expression level of VEGF was increased in curcumin treated cells at first 24 h time period. Based on data from the current experiment, the protein level of p-FAK/FAK ratio was increased coincided with a decrease in p-P38/P38 ratio treatment with curcumin (p < 0.0001). These data demonstrated that curcumin inhibited HUVECs angiogenesis potential by modulation of FAK/P-38 MAPK signaling pathway.
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http://dx.doi.org/10.1016/j.gene.2018.11.062DOI Listing
March 2019

Bio-Effects of TiO2 Nanoparticles on Human Colorectal Cancer and Umbilical Vein Endothelial Cell Lines

Asian Pac J Cancer Prev 2018 Oct 26;19(10):2821-2829. Epub 2018 Oct 26.

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran. Email:

Background: Due to the possible biomedical potential of nanoparticles, titanium dioxide nanoparticles (TiO2 NPs) have received great attention in cancer research. Although selectivity of cytotoxicity with TiO2 NPs in various cells is clinically significant comparisons of cancer and non-cancer cells have been limited. Therefore, we here studied exposure to TiO2 NPs in colorectal cancer cells (CRCs) and human umbilical vein endothelial cells (HUVECs). Methods: After characterization of TiO2 NPs, culture and treatment of cells (HCT116, HT29 and HUVEC), viability was assessed by MTT assay and in terms of morphological features. Acridine orange (AO) and propidium iodide (PI) assays were carried out to estimate the incidence of apoptosis. The RT-PCR method was also employed to evaluate the expression of P53, Bax, Bcl-2 and Caspase 3. Results: Exposure to increasing concentrations of TiO2 NPs enhanced overall cell survival of HCT116 cells and reduced the Bcl-2 and Caspase 3 expression while the ratio of Bax/Bcl-2 was down-regulated. TiO2 NPs at 400 and 50 μg/ml concentrations suppressed cell proliferation and induced apoptosis of HT29 cells and also up-regulated P53 and Bax at the mRNA level, enhanced the Bax/Bcl-2 ratio and eventually up-regulated Caspase 3 mRNA. Although, inhibition of cell proliferation in HUVECs was seen at 200 and 400 μg/ml TiO2 NPs, it was not marked. Conclusion: TiO2 NPs have selective bio-effects on exposed cells with dose- and cell-dependent influence on viability. Cell proliferation in HCT116 as a metastatic colorectal cancer cell line appeared to be stimulated via multiple signaling pathways, with promotion of apoptosis in less metastatic cells at 50 and 400 μg/ml concentrations. This was associated with elevated P53, Bax and Caspase 3 mRNA and reduced Bcl-2 expression. However, TiO2 NPs did not exert any apparent significant effects on HUVECs as hyperproliferative angiogenic cells.
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http://dx.doi.org/10.22034/APJCP.2018.19.10.2821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6291037PMC
October 2018

Effect of early-life inflammation and magnesium sulfate on hyperthermia-induced seizures in infant rats: Susceptibility to pentylenetetrazol-induced seizures later in life.

Dev Psychobiol 2019 01 18;61(1):96-106. Epub 2018 Oct 18.

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

This study investigated the effect of inflammation and MgSO pretreatment on behaviors caused by hyperthermia (HT) and the effect of these interventions on PTZ-induced seizure a week later. In this experimental study, rat pups experienced inflammation on postnatal day 10 (P10). On P18-19, the pups received either saline or MgSO then subjected to hyperthermia. On P25-26, PTZ-induced seizure was initiated in the rats. Neonatal inflammation increased the susceptibility to HT-induced seizure. Inflammation and HT increased the susceptibility to PTZ-induced seizure. Pretreatment with MgSO before hyperthermia decreased the susceptibility to both HT- and PTZ-induced seizure. Furthermore, calcium and magnesium blood levels significantly decreased compared to control rats. It can be concluded that neonatal inflammation potentiates while pretreatment with MgSO attenuates HT-induced seizures. Also, neonatal inflammation and HT potentiate PTZ-induced seizure initiated one week later.
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http://dx.doi.org/10.1002/dev.21781DOI Listing
January 2019

Effect of prenatal stress on ɑ5 GABA receptor subunit gene expression in hippocampus and pilocarpine induced seizure in rats.

Int J Dev Neurosci 2018 08 11;68:66-71. Epub 2018 May 11.

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

The GABAergic synapses go through structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in developing brain, which are associated with the pathophysiology of neuropsychiatric disorders in adults. The present study aimed to investigate the effect of prenatal restraint stress (PS) on pilocarpine-induced seizure and ɑ5 subunit of γ-amino butyric acid type A (GABA) receptor expression in hippocampus. Pregnant Wistar rats were subjected to PS at gestational days 15-17 and the pups were examined for susceptibility to seizure and ɑ5 subunit of GABA receptor expression in hippocampus at postnatal days 14 and 21 (P14 and PND 21). Quantitative real-time PCR was used for evaluating the gene expression in the pups. Pilocarpine was injected intraperitoneally into the pups and seizure behaviors were recorded. The results showed that ɑ5 subunit mRNA expression significantly increased in hippocampus at both the P14 and P21 in the stressed rats. However, ɑ5 subunit level was greater at the P21 than at the P14 in both the groups. Latency of first tonic-clonic seizure significantly decreased in the PS group compared to the control pups. Number and duration of tonic-clonic seizures increased in the PS rats compared to the controls. PS led to an increase in total score of seizure at the P14 and P21. It can be concluded that PS increases the seizure susceptibility and GABA receptor ɑ5 subunit gene expression in offspring; it is likely that the mechanism of increased seizure susceptibility by PS, at least in part, can increase the GABA receptor ɑ5 subunit gene expression in hippocampus.
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http://dx.doi.org/10.1016/j.ijdevneu.2018.05.003DOI Listing
August 2018

Correlation of nerve fibers in corpus callosum and number of neurons in cerebral cortex: an innovative mathematical model.

Int J Neurosci 2018 Oct 13;128(10):995-1002. Epub 2018 Apr 13.

b Department of Anatomy, Faculty of medicine , Urmia University of Medical Sciences , Urmia Iran.

Purpose/aim: It is estimated that 10 bits/s information are processed in the human brain. The transmission of this huge amount of information requires all connections in the brain to be highly accurate and have order. The current study attempted to present a new aspect of order and proportion in the ultra-structure of the human brain and to calculate the degree of neural interdependence between the two hemispheres.

Materials And Methods: In this model, intensity of interdependence of the brain to hemispheres is estimated to be equal to the mathematical proportion of number of neurons in cerebral cortex divided by 2 (number of hemispheres), divided by number of nerve fibers in the human corpus callosum.

Results: The calculated number is equal to 30-50 and it indicates that for every 30-50 neurons between the two hemispheres, there is a neural interconnecting bridge.

Conclusions: This connection indicates that the brain's function output follows a mathematical relation.
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http://dx.doi.org/10.1080/00207454.2018.1458725DOI Listing
October 2018

Pregestational stress attenuated fertility rate in dams and increased seizure susceptibility in offspring.

Epilepsy Behav 2018 02 4;79:174-179. Epub 2018 Jan 4.

Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Many studies have found that stress during pregnancy is linked to an increased incidence of epileptic behaviors and reproductive disorders. However, few works have investigated the effect of pregestational stress on seizure susceptibility in the offspring. We investigated the effect of pregestational stress on epileptic behaviors in the offspring as well as fertility rate in dams. The male and female rats were randomly divided into four groups to form a combination of control and stressed groups for each sex. The rats were subjected to predatory stress (exposed to a cat) twice per day for 50 (male) and 15 (female) consecutive days. At the end of the stress procedure, the rats were coupled as follows: both male and female control (M-F), male stressed/female control (M-F), male control/female stressed (M-F), and both male and female stressed (M-F). Then, the puppies born from these groups were counted and evaluated for pentylentetrazole (PTZ)-induced seizure. There was no significant difference between the male and female pups in each identical group in terms of litter size and epileptic behaviors, except duration of tail rigidity and duration of immobility. The total score of seizure increased in all the stressed groups, but more severely in the M-F group. However, the onset of the first epileptic behavior and tonic-clonic seizure significantly decreased in the stressed groups. Moreover, fertility rate significantly decreased in the stressed groups compared with the control group, but there was no significant difference in terms of litter size between the groups. These data revealed the impact of pregestational stress during spermatogenesis and oogenesis on fertility rate in dams and epileptic behaviors in the offspring.
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http://dx.doi.org/10.1016/j.yebeh.2017.12.016DOI Listing
February 2018

Transcriptional activity of tumor necrosis factor-alpha gene in peripheral blood mononuclear cells in patients with coronary slow flow.

ARYA Atheroscler 2017 Jul;13(4):196-201

Associate Professor, Department of Physiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran.

Background: Coronary slow flow (CSF), an angiographic phenomenon that is characterized by a delayed coronary blood flow in the absence of obstructive coronary artery stenosis, is known as a disorder of the coronary microcirculation. Inflammation has an important role in the vascular hemostasis and endothelial dysfunction especially regarding monocyte adhesion and infiltration. Pro-inflammatory cytokines released by inflammatory cells result in endothelial cell dysfunction and cardiovascular diseases. It has been demonstrated that tumor necrosis factor-alpha (TNF-α) mainly influences the vascular homeostasis and endothelial dysfunction. In the present enquiry the transcriptional activity of TNF-α gene in peripheral blood mononuclear cells (PBMCs) of patients with CSF was compared with healthy controls in order to further survey the role of TNF-α in pathophysiology of CSF.

Methods: The study was carried out on 30 patients with CSF and 30 matched healthy controls. To analysis gene expression of TNF-α, total mRNA was isolated from PBMCs. The quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was used to compare the transcriptional activity of TNF-α gene between patients with CSF and controls.

Results: The mean ± standard error of mean of fold in CSF patients and controls were 0.20 ± 0.04 and 1.38 ± 0.27, respectively. The mRNA mean expressions of TNF-α (fold) were different in tested groups, which indicated a significant decrease in TNF-α in patients with CSF group (P = 0.0001).

Conclusion: Expression of TNF-α was decreased in patients with CSF. Changes in TNF-α expression suggest a potential role for altered immune function in the pathophysiology of CSF.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5677324PMC
July 2017

Prenatal stress potentiates febrile seizure and leads to long-lasting increase in cortisol blood levels in children under 2years old.

Epilepsy Behav 2017 07 29;72:22-27. Epub 2017 May 29.

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

Neurological disorders can be exacerbated in an offspring that is exposed to stress prenatally. This study is aimed to investigate the severity of febrile seizures (FS) in the offspring under 2years old that were prenatally stressed. In this study, 158 children below 2years old with FS were selected. Information about convulsion including seizure lasting, recurrence of seizure, age of the first seizure and type of FS was gathered. Blood samples were obtained from the offspring to measure the cortisol blood levels. Questionnaire was filled in to evaluate the perceived stress and exposure or non-exposure to major stresses during pregnancy. Results of this study showed that both high Perceived Stress Scores (PSS) during pregnancy and exposure to major stresses during pregnancy significantly increased seizure duration and seizure intensity. Also, the appearance of complex FS was significantly higher in prenatally stressed children than the unexposed ones. Further, cortisol blood levels were significantly higher in prenatally stressed subjects. It can be concluded that both higher PSS and/or exposure to major stresses during pregnancy potentiate FS parameters and lead to long lasting increase in cortisol blood levels in the offspring.
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http://dx.doi.org/10.1016/j.yebeh.2017.04.021DOI Listing
July 2017

Effects of Pulsed Electromagnetic Field with Predatory Stress on Functional and Histological Index of Injured-Sciatic Nerve in Rat.

Bull Emerg Trauma 2017 Apr;5(2):96-103

Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran.

Objective: To assess the effect of combination of pulsed electromagnetic fields (PEMF) with predatory stress on transected sciatic nerve regeneration in rats.

Methods: In sham- operated group (SOG) the nerve was manipulated and left intact. The 10-mm rat sciatic nerve gap was created in rats. In transected group (Transected) nerve stumps were sutured to adjacent muscle and in vein graft group (VG) the gap was bridged using an inside-out vein graft. In VG/PEMF group the transected nerve was bridged using vein graft, phosphate buffered saline was administered into the graft and the whole body was exposed to PEMF. In VG/PS group the transected nerve was bridged using vein graft, phosphate buffered saline was administered into the graft and the rats underwent predatory stress (PS).  In VG/PEMF/PS group the transected nerve was bridged using vein graft, phosphate buffered saline was administered into the graft, the whole body was exposed to PEMF and the rats underwent predatory stress. The regenerated nerve fibers were studied within 12 weeks after surgery.

Results: Functional, gastrocnemius muscle mass findings and morphometric indices confirmed faster recovery of regenerated axons in VG/PEMF and VG/PEMF/PS groups compared to those in the other groups (=0.001). The whole body exposure to PEMF improved functional recovery. Predatory stress did not affect nerve regeneration in the animals undergone predatory stress (=0.343).

Conclusion: Pulsed electromagnetic fields could be considered as an effective, safe and tolerable treatment for peripheral nerve repair in clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406179PMC
April 2017

The effect of selective opioid receptor agonists and antagonists on epileptiform activity in morphine-dependent infant mice hippocampal slices.

Int J Dev Neurosci 2017 Aug 25;60:56-62. Epub 2017 Apr 25.

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran. Electronic address:

Hippocampal slices of mouse brain were used to estimate how selective agonist and antagonist of opioid receptors alter Low-Mg artificial cerebrospinal fluid (LM-ACSF)-induced epileptiform activities in normal and morphine-dependent mice. Brain slices were obtained from control and morphine-dependent mice. The morphine-dependent group received morphine once a day for 5 consecutive days, and the control group received saline. All injections were administered subcutaneously (s.c) in a volume of 0.1mL on postnatal days 14-18. Brain slices were perfused with LM-ACSF along with selective agonist and antagonist of μ, κ and δ opioid receptors. Changes in spike count per unit of time were used as indices to quantify the effects of LM-ACSF exposure in the slices. In both groups, DAMGO (selective μ opioid receptor agonist) and DPDPE (selective δ opioid receptor agonist) suppressed while Dyn-A (selective κ opioid receptor agonist) potentiated the epileptiform activity. Meanwhile, BFN-A (selective μ opioid receptor antagonist) recovered epileptiform activity in normal brain slices but not in morphine-dependent ones. NTI (selective δ opioid receptor antagonist) and nor-BNI (selective κ opioid receptor antagonist) decreased epileptiform activity. It seems that the excitatory effect of morphine on epileptiform activity was mediated through kappa receptors and its inhibitory effect was mediated via the mu receptor and, to a lesser degree, through the delta receptor. The pattern of effect was similar in normal and morphine-dependent slices, but the intensity of the effect was significantly stronger in normal mice. Finding of this study might be considered for further research and attention in epilepsy treatment.
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http://dx.doi.org/10.1016/j.ijdevneu.2017.04.003DOI Listing
August 2017

Effect of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration and anxiety behaviors in adult rat offspring.

Stress 2017 03 28;20(2):205-211. Epub 2017 Mar 28.

d Cellular and Molecular Research Center, Urmia University of Medical Sciences , Urmia , Iran.

Stressful events and exposure to opiates during gestation have important effects on the later mental health of the offspring. Anxiety is among the most common mental disorders. The present study aimed to identify effects of prenatal restraint stress and morphine co-administration on plasma vasopressin concentration (PVC) and anxiety behaviors in rats. Pregnant rats were divided into four groups (n = 6, each): saline, morphine, stress + saline and stress + morphine treatment. The stress procedure consisted of restraint twice per day, two hours per session, for three consecutive days starting on day 15 of pregnancy. Rats in the saline and morphine groups received either 0.9% saline or morphine intraperitoneally on the same days. In the morphine/saline + stress groups, rats were exposed to restraint stress and received either morphine or saline intraperitoneally. All offspring were tested in an elevated plus maze (EPM) on postnatal day 90 (n = 6, each sex), and anxiety behaviors of each rat were recorded. Finally, blood samples were collected to determine PVC. Prenatal morphine exposure reduced anxiety-like behaviors. Co-administration of prenatal stress and morphine increased locomotor activity (LA) and PVC. PVC was significantly lower in female offspring of the morphine and morphine + stress groups compared with males in the same group, but the opposite was seen in the saline + stress group. These data emphasize the impact of prenatal stress and morphine on fetal neuroendocrine development, with long-term changes in anxiety-like behaviors and vasopressin secretion. These changes are sex specific, indicating differential impact of prenatal stress and morphine on fetal neuroendocrine system development. Lay Summary Pregnant women are sometimes exposed to stressful and painful conditions which may lead to poor outcomes for offspring. Opiates may provide pain and stress relief to these mothers. In this study, we used an experimental model of maternal exposure to stress and morphine in pregnant rats. The findings indicated that maternal stress increased anxiety in offspring while morphine decreased such effects, but had negative effects on the levels of a hormone controlling blood pressure, and activity of offspring. Hence morphine should not be used in pregnancy for pain and stress relief.
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http://dx.doi.org/10.1080/10253890.2017.1306053DOI Listing
March 2017