Publications by authors named "Mahsa Pourhamzeh"

5 Publications

  • Page 1 of 1

The Roles of Serotonin in Neuropsychiatric Disorders.

Cell Mol Neurobiol 2021 Mar 2. Epub 2021 Mar 2.

Division of Neuroscience, Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.

The serotonergic system extends throughout the central nervous system (CNS) and the gastrointestinal (GI) tract. In the CNS, serotonin (5-HT, 5-hydroxytryptamine) modulates a broad spectrum of functions, including mood, cognition, anxiety, learning, memory, reward processing, and sleep. These processes are mediated through 5-HT binding to 5-HT receptors (5-HTRs), are classified into seven distinct groups. Deficits in the serotonergic system can result in various pathological conditions, particularly depression, schizophrenia, mood disorders, and autism. In this review, we outlined the complexity of serotonergic modulation of physiologic and pathologic processes. Moreover, we provided experimental and clinical evidence of 5-HT's involvement in neuropsychiatric disorders and discussed the molecular mechanisms that underlie these illnesses and contribute to the new therapies.
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http://dx.doi.org/10.1007/s10571-021-01064-9DOI Listing
March 2021

Time-Dependent Changes in the Serum Levels of Neurobiochemical Factors After Acute Methadone Overdose in Adolescent Male Rat.

Cell Mol Neurobiol 2020 Jul 25. Epub 2020 Jul 25.

Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, P.O. Box: 19615-1178, Tehran, Iran.

Acute methadone toxicity is a major public health concern which has adverse effects on brain tissue and results in recurrent or delayed respiratory arrest. Our study aimed to investigate the time-dependent changes in several serum biochemical markers of brain damage, spatial working memory, and the brain tissue following acute methadone overdose. Adolescent male rats underwent an intraperitoneal (i.p.) injection of 15 mg/kg methadone. In case of apnea occurrence, resuscitation was performed by a ventilatory pump and administrating naloxone (2 mg/kg; i.p.). The animals were classified into groups of treated rats; methadone and naloxone-Apnea (M/N-Apnea), M/N-Sedate, Methadone, Naloxone, and control (saline) groups. The serum levels of S100B, neuron-specific enolase (NSE), myelin basic protein factors, and (Lactate/Pyruvate) L/P ratio were evaluated at the time-points of 6, 24, and 48 h (h). We found that the alterations of S100B and L/P ratio were considerable in the M/N-Apnea and Methadone groups from the early hours post-methadone overdose, while NSE serum levels elevation was observed only in M/N-Apnea group with a delay at 48 h. Further, we assessed the spatial working memory (Y-maze test), morphological changes, and neuronal loss. The impaired spontaneous alternation behavior was detected in the M/N-Apnea groups on days 5 and 10 post-methadone overdose. The morphological changes of neurons and the neuronal loss were detectable in the CA1, striatum, and cerebellum regions, which were pronounced in both M/N-Apnea and Methadone groups. Together, our findings suggest that alterations in the serum levels of S100B and NSE factors as well as L/P ratio could be induced by methadone overdose with the presence or absence of apnea before the memory impairment and tissue injury in adolescent male rats.
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http://dx.doi.org/10.1007/s10571-020-00931-1DOI Listing
July 2020

The Interplay of Tau Protein and β-Amyloid: While Tauopathy Spreads More Profoundly Than Amyloidopathy, Both Processes Are Almost Equally Pathogenic.

Cell Mol Neurobiol 2020 Jul 22. Epub 2020 Jul 22.

Department of Brain and Cognitive Sciences, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.

Alzheimer's disease (AD) is a neurodegenerative disorder, in which amyloid precursor protein (APP) misprocessing and tau protein hyperphosphorylation are well-established pathogenic cascades. Despite extensive considerations, the central mediator of neuronal cell death upon AD remains under debate. Therefore, we examined the direct interplay between tauopathy and amyloidopathy processes. We employed primary culture neurons and examined pathogenic P-tau and Aβ oligomers upon hypoxia treatment by immunofluorescence and immunoblotting. We observed both tauopathy and amyloidopathy processes upon the hypoxia condition. We also applied Aβ or P-tau onto primary cultured neurons. We overexpressed P-tau in SH-SY5Y cells and found Aβ accumulation. Furthermore, adult male rats received Aβ or pathogenic P-tau in the dorsal hippocampus and were examined for 8 weeks. Learning and memory performance, as well as anxiety behaviors, were assessed by Morris water maze and elevated plus-maze tests. Both Aβ and pathogenic P-tau significantly induced learning and memory deficits and enhanced anxiety behavior after treatment 2 weeks. Aβ administration induced robust tauopathy distribution in the cortex, striatum, and corpus callosum as well as CA1. On the other hand, P-tau treatment developed Aβ oligomers in the cortex and CA1 only. Our findings indicate that Aβ and pathogenic P-tau may induce each other and cause almost identical neurotoxicity in a time-dependent manner, while tauopathy seems to be more distributable than amyloidopathy.
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http://dx.doi.org/10.1007/s10571-020-00906-2DOI Listing
July 2020

The blockade of D1- and D2-like dopamine receptors within the dentate gyrus attenuates food deprivation stress-induced reinstatement of morphine-extinguished conditioned place preference in rats.

Pharmacol Biochem Behav 2020 09 15;196:172967. Epub 2020 Jun 15.

Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The high rate of relapse to drug abuse is one of the main problems in the treatment of addiction. Stress plays an essential role in relapsing to drug abuse. The present study investigates the role of D1- and D2-like dopamine receptors in the dentate gyrus (DG) of the hippocampus on the reinstatement of morphine (5 mg/kg)-induced conditioned place preference (CPP) both by food deprivation stress (FDS) and a sub-threshold dose of morphine (0.5 mg/kg, s.c.). All the animals in this study experienced pre-test, conditioning, post-test (expression), extinction, and reinstatement phases. The CPP scores of the pre-test and post-test were compared between the groups, and a significant difference between the CPP scores of the pre- and post-test was the criterion for the induction of CPP. Extinction continued for each animal until the calculated score for two consecutive days became the same as the pre-test score. The animals received different doses of SCH-23390 or Sulpiride (0.25, 1 and 4 μg/0.5 μl vehicle), as D1- and D2-like dopamine receptor antagonists, into the DG. After the administration of the antagonists, the animals were deprived of food for 24 h. Then, on the reinstatement day, they received a sub-threshold dose of morphine and afterwards, the conditioning scores were measured. The results demonstrated that the effective doses 50% of SCH-23390 and Sulpiride on the reinstatement induced by FDS and morphine was 1.37 and 2.28 (μg/0.5 μl vehicle per side), respectively. The results also showed that both antagonists can lead to a decrease in morphine reinstatement, and this effect was in a dose-dependent manner. In conclusion, these results indicate that D1- and D2-like dopamine receptors in the DG may be a potential target for preventing relapse to drugs in stressful life conditions.
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http://dx.doi.org/10.1016/j.pbb.2020.172967DOI Listing
September 2020

Involvement of orexin receptors within the hippocampal dentate gyrus in morphine-induced reinstatement in food-deprived rats.

Behav Brain Res 2019 12 15;375:112155. Epub 2019 Aug 15.

Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:

The orexinergic system is found to cooperate in mediating stress-induced drug relapse. The orexinergic terminals innervate neurons of the hippocampal dentate gyrus (DG) which is a key structure in the maintenance and reinstatement of drug addiction. However, the specific contribution of intra-DG orexin receptors to stress-induced reinstatement has not been completely known. In the current study, the effects of intra-DG administration of SB334867, an orexin-1 receptor (OX1R) antagonist, and TCS OX2 29, an orexin-2 receptor (OX2R) antagonist, were investigated on the reinstatement induced by a sub-threshold dose of morphine and food deprivation (FD) stress. Adult male rats received different doses of SB334867 or TCS OX2 29 (3, 10, and 30 nM/0.5 μl DMSO 12%) bilaterally into the DG in separate groups, following the acquisition and extinction of morphine-induced conditioned place preference (CPP). Then, the reinstatement was evaluated by the 24 h FD stress and/or a sub-threshold dose of morphine (0.5 mg/kg, s.c.). CPP scores and locomotor activities were recorded during the test. The findings indicated that pre-treatment with the highest dose of SB334867 (30 nM) and two higher doses of TCS OX2 29 (10 and 30 nM) blocked the sub-threshold dose and FD stress-induced reinstatement of morphine. The effect of TCS OX2 29 on reduction of reinstatement was more pronounced than that of SB334867. It suggests a role for the orexin receptors, especially OX2R within the DG region in the stress-induced reinstatement of morphine-seeking behaviours in extinguished rats.
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http://dx.doi.org/10.1016/j.bbr.2019.112155DOI Listing
December 2019