Publications by authors named "Ali Shahbazi"

31 Publications

An integrative gene network-based approach to uncover the cellular and molecular infrastructures of schizophrenia.

Life Sci 2020 Nov 24;260:118345. Epub 2020 Aug 24.

Cellular and Molecular Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran. Electronic address:

Aims: High phenotypic and endophenotypic heritability of schizophrenia indicates substantial involvement of genetic elements in the occurrence of this disorder. Multiplicity of hypotheses about the genetic basis of schizophrenia pathogenesis suggests that there is still no integrated image from cellular and molecular infrastructure of this disorder.

Materials And Methods: Here, we aimed to gain an integrated insight into the genetic basis of schizophrenia through gene set enrichment and network analysis to find the most important developmental stages/brain regions, chromosomal locations and metabolic pathways involved in the pathogenesis of schizophrenia. We investigated major mental disorders whose genetic bases are significantly overlapping with the schizophrenia gene set.

Key Findings: Enrichment analyses uncovered 60 developmental stages/brain regions, 21 chromosomal hotspots and 16 pathways which are significantly associated with the found gene set. Our results demonstrated early mid-fetal/cortex as the most prominent developmental stage/brain region, chr16q22 as the most significant cytoband and the neuroactive ligand-receptor interaction as the most central pathway associated with schizophrenia. Further analyses revealed that autistic disorder has the most shared genes with schizophrenia. Moreover, mitogen-activated protein kinase-3 (MAPK3), calcium voltage-gated channel subunit alpha1 C (CACNA1C), solute carrier family 6 member 4 (SLC6A4) and 5-hydroxytryptamine receptor 2A (HTR2A) genes are the most central genes in the pathogenesis of schizophrenia.

Significance: In addition to summarizing what has been found on schizophrenia-associated genes in an integrative holistic framework, our results may help identify principle schizophrenia-associated cellular and molecular infrastructures, and provide support for further investigation on potential diagnostic and therapeutic biomarkers for schizophrenia.
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http://dx.doi.org/10.1016/j.lfs.2020.118345DOI Listing
November 2020

A Novel Link between the Oxytocin Receptor Gene and Impulsivity.

Neuroscience 2020 09 25;444:196-208. Epub 2020 Jul 25.

Cellular and Molecular Research Center, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences (IUMS), Tehran, Iran. Electronic address:

Impulsivity includes hasty actions, social intrusiveness or premature decision-making. Neuropeptides like oxytocin alleviate haste and anxiety, and affect fear conditioning. However, no investigations have been done via gene-network based approach with cognitive and interventional genetic association studies to scrutinize the link between impulsive behavior and oxytocin. Here, interactive gene network and pathways associated with impulsivity were reconstructed, and serotonin transporter gene (SLC6A4) and serotoninergic synaptic transmission were identified as the most central gene and pathway related to impulsivity. Young healthy males received intranasal oxytocin or placebo, and impulsivity was evaluated via go/no-go test. Test performance scores then were analyzed based on commission and omission errors, response inhibition and reaction time. Blood DNA was extracted and a 761 bp intronic region in oxytocin receptor (OXTR) gene was amplified and sequenced using PCR-pyrosequencing. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all SNPs in the target sequence were determined based on D' and LOD values, and rs2254298 with the highest LD was indicated as the tag SNP. Oxytocin group and participants with GG genotype showed a significantly decreased commission error and increased inhibition. This means that oxytocin alleviated impulsive behavior, and subjects with GG genotype had lower rate of impulsivity than those with GA and AA genotypes. rs2254298 may modulate the function or expression of the OXTR gene, implying that G allele may increase the expression of OXTR gene compared to A allele. We suggest that intranasal oxytocin may notably moderate impulsive behavior and tendency to make hasty or premature decisions.
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http://dx.doi.org/10.1016/j.neuroscience.2020.07.033DOI Listing
September 2020

Genotyping of Fresh and Parafinized Human Hydatid Cysts Using and Genes in Hamadan Province, West of Iran.

Iran J Parasitol 2020 Apr-Jun;15(2):259-265

Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Background: Hydatidosis is a cosmopolitan zoonotic infection and Hamadan Province in the west of Iran is one of the most important foci of human hydatidosis in Iran. The aim of the current study was the genetic characterization of hydatid cysts operated from humans in Hamadan Province.

Methods: Seventy-two hydatid cysts samples including 50 paraffinized and 22 fresh human hydatid cysts collected from different hospitals in Hamadan Province, western Iran. The cysts' DNA genome was extracted by kit and PCR was performed for amplifying the fragments of 400 and 450bp for and mitochondrial genes, respectively. Genotype diversity and sequence variations of the cysts' isolates were studied by related software.

Results: DNA from all (100%) paraffinized and fresh hydatid cysts samples extracted successfully. All paraffinized and fresh hydatid cysts samples were amplified by PCR assay using gene, however, only 18 and 8 samples from paraffinized and fresh hydatid cyst samples was amplified using gene, respectively. The sequences analysis indicated that, 98.61% the samples were belong to the genotype G1 and 1.39% were G3 genotype.

Conclusion: Genotypes of in human samples in Hamadan Province are G1 and G3 and these findings are proved by phylogenic analysis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311807PMC
June 2020

COVID-19 virus may have neuroinvasive potential and cause neurological complications: a perspective review.

J Neurovirol 2020 06 16;26(3):324-329. Epub 2020 May 16.

Neuroscience Research Center, Mashhad University of Medical Sciences , Mashhad, Iran.

Coronavirus disease 2019 (COVID-19) was reported at the end of 2019 in China for the first time and has rapidly spread throughout the world as a pandemic. Since COVID-19 causes mild to severe acute respiratory syndrome, most studies in this field have only focused on different aspects of pathogenesis in the respiratory system. However, evidence suggests that COVID-19 may affect the central nervous system (CNS). Given the outbreak of COVID-19, it seems necessary to perform investigations on the possible neurological complications in patients who suffered from COVID-19. Here, we reviewed the evidence of the neuroinvasive potential of coronaviruses and discussed the possible pathogenic processes in CNS infection by COVID-19 to provide a precise insight for future studies.
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http://dx.doi.org/10.1007/s13365-020-00851-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229881PMC
June 2020

Neuroprotective effects of cerium oxide nanoparticles on experimental stress-induced depression in male rats.

J Chem Neuroanat 2020 07 3;106:101799. Epub 2020 May 3.

Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Science, Tehran, Iran.

Introduction: Inflammation and oxidative/nitrative stress induced by chronic psychosocial or physical stress play fundamental roles in the pathogenesis of depression, and lead to the loss of neurotrophic support, decreased neurogenesis and synaptic plasticity in the hippocampus. Findings have shown inhibition of inflammation waterfall may offer new approaches to the treatment of depression, especially for patients with treatment-resistant depression (TRD). Cerium Oxide (CeO) is the oxide form of cerium, a rare earth element in the lanthanide series. Cerium oxide nanoparticles (CeONPs) are potent regenerative antioxidant and anti-inflammatory agents. We evaluated the neuroprotective and the neuronal plasticity activities of CeONPs in the stress-induced model of depression.

Methods: We have analyzed the effects of single-dose intrahippocampal and intracerebroventricular (ICV) injections of CeONPs treatment on immobility behavior (forced swimming test), hippocampal IL-6 and malondialdehyde (Elisa), cell survival (Nissl staining), dentate gyrus BrdU-positive cells (Immunohistofluorescence) and growth associated protein-43 (GAp-43) expression (Immunohistofluorescence) of the hippocampal CA3 region.

Results: In our study, single-dose CeONPs treatment could effectively suppress inflammatory and oxidative markers level induced by unpredictable chronic mild stress (UCMS) and improved immobility behavior, increased hippocampal cell proliferation, cell survival and neurite outgrowth, and thereby, prevented the progression of hippocampal destruction and dysfunction.

Conclusion: This study demonstrates a new prospect for the treatment of depression. Our study gives us the confidence to continue the investigation of CeO NPs as a novel therapy, especially, for TRD that characterized by chronic and persistent inflammation.
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http://dx.doi.org/10.1016/j.jchemneu.2020.101799DOI Listing
July 2020

Combined Effect of Noise and Smoking on the Cognitive Performance of Automotive Industry Workers.

Basic Clin Neurosci 2019 Sep-Oct;10(5):515-526. Epub 2019 Sep 1.

Department of Epidemiology and Biostatistics, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Noise is an environmental stressor and can cause or exacerbate mental disorders, and affect the individual performance in certain conditions. This study aimed to evaluate the combined effects of noise and smoking on the cognitive performance of the workers in the automotive industry.

Methods: This research is a descriptive-analytical study with a cross-sectional design conducted on 300 workers randomly assigned into two groups of noise-exposed and nonexposed. They were examined using computerized tests, including the Tower of London test (TOL), Continuous Performance test (CPT), and Stroop test. The sound pressure levels were measured based on an 8-hour equal-loudness contour in each group according to ISO 9612 standard, using the Testo CEL-815 sound level meter.

Results: The study of combined effects of noise and smoking on 12 CPT indicators using the 2-way Analysis of Variance (ANOVA) indicate that noise and smoking factors had a significant impact on the mean number of errors and correct responses in the third 50-stimuli stage, the mean number of errors and correct responses in the second 50-stimuli stage with P<0.001, P<0.001, P=0.012 and P<0.001 for smoking respectively, but only noise affected the other 7 indicators (P<0.001).

Conclusion: Smoking and noise have negative impacts on concentration, attention, and cognitive processing speed, which can lead to an individual's mistakes and delayed decision making at the workplace.
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http://dx.doi.org/10.32598/bcn.10.5.513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7149955PMC
September 2019

Astrocyte swelling in hepatic encephalopathy: molecular perspective of cytotoxic edema.

Metab Brain Dis 2020 04 7;35(4):559-578. Epub 2020 Mar 7.

The Institute of Hepatology London and Foundation for Liver Research, 111 Coldharbour Lane, London, SE5 9NT, UK.

Hepatic encephalopathy (HE) may occur in patients with liver failure. The most critical pathophysiologic mechanism of HE is cerebral edema following systemic hyperammonemia. The dysfunctional liver cannot eliminate circulatory ammonia, so its plasma and brain levels rise sharply. Astrocytes, the only cells that are responsible for ammonia detoxification in the brain, are dynamic cells with unique phenotypic properties that enable them to respond to small changes in their environment. Any pathological changes in astrocytes may cause neurological disturbances such as HE. Astrocyte swelling is the leading cause of cerebral edema, which may cause brain herniation and death by increasing intracranial pressure. Various factors may have a role in astrocyte swelling. However, the exact molecular mechanism of astrocyte swelling is not fully understood. This article discusses the possible mechanisms of astrocyte swelling which related to hyperammonia, including the possible roles of molecules like glutamine, lactate, aquaporin-4 water channel, 18 KDa translocator protein, glial fibrillary acidic protein, alanine, glutathione, toll-like receptor 4, epidermal growth factor receptor, glutamate, and manganese, as well as inflammation, oxidative stress, mitochondrial permeability transition, ATP depletion, and astrocyte senescence. All these agents and factors may be targeted in therapeutic approaches to HE.
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http://dx.doi.org/10.1007/s11011-020-00549-8DOI Listing
April 2020

Valproic acid administration exerts protective effects against stress-related anhedonia in rats.

J Chem Neuroanat 2020 04 13;105:101768. Epub 2020 Feb 13.

Department of Biotechnology, School of Allied Medical Science, Iran University of Medical Science, Tehran, Iran.

Anhedonia or inability to experience pleasure is the sign of various neuropsychiatric conditions. Current treatment options do not provide adequate control of anhedonia. The present study was conducted to evaluate the protective effects of valproic acid (VPA) as a nonspecific histone deacetylase (HDAC) inhibitor to reverse the effects of stress on induction of anhedonia and explore possible mechanisms. To induce anhedonia, a rat model of chronic unpredictable mild stress (CUMS) was established. Animals were assigned into no stress, stress (6 weeks of CUMS) and two treatment groups. VPA treatment was carried out for 4 continuous weeks (200 mg/kg/day). Behavioral assessments were performed using sucrose consumption (SCT) and new object recognition (NOR) tests. The expression of genes was evaluated using qRT-PCR. The cell density was determined using Nissl staining. Rats with CUMS showed depressive-like behaviors and impaired memory performance compared with the non-stressed group (p < 0.01). Moreover, they had significantly higher levels of HDAC3 and MC4R expression in the nucleus accumbens (NAc) compared to the non-stressed group (p < 0.01). The NAc cell density was significantly higher in the non-stressed rats (p < 0.05). Corticosterone plasma level was increased in the CUMS compared to the non-stressed group (p < 0.05). In the CUMS + VPA subgroup, the corticosterone (CORT) plasma level was lower compared with the CUMS + Saline and/or the CUMS groups (p < 0.05). These findings suggest that VPA can improve anhedonia and stress. Although the protective effect of VPA might link to decreasing HDAC3 and MC4R genes expression in NAc.
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http://dx.doi.org/10.1016/j.jchemneu.2020.101768DOI Listing
April 2020

The effect of insular cortex lesion on hyperacusis-like behavior in rats.

Int J Neurosci 2020 Nov 7;130(11):1071-1081. Epub 2020 Apr 7.

Department of Audiology, School of Rehabilitation, Tehran University of Medical Sciences, Tehran, Iran.

Hyperacusis is hypersensitivity and extreme response to the intensity of sound that is tolerable in normal subjects. The mechanisms underlying hyperacusis has not been well understood, specially the role of insular cortex. The aim of this study is to investigate the role of insular cortex in hyperacusis like behavior. The number of 33 male wistar rats weighting 170-250 gr were allocated randomly in three groups; control, sham, and insular lesion. Auditory startle responses (ASR) to different intensities of stimuli (70, 80, 90, 100, and110 dB without background noise as well as 110 dB in the presence of 70, 80 dB background noise) were measured before and up to four weeks after intervention. Data analyses showed an increase in ASR to 100 dB stimulus without background noise one week after insular lesion, and increased responses to other intensities two weeks after lesion. Furthermore, there was a decrease in ASR to 110 dB stimulus with 80 dB background noise two weeks after insular lesion. However, no significant difference was observed in 70 dB background noise. The changes in ASR lasts at least four weeks. The findings indicated that there was an increase in ASR in the absence of background noise following cortical excititoxic lesion limited to insular cortex, while there was a decrease in responses in the presence of background noise which suggests possible increased sensitivity to sound loudness as a hyperacusis-like phenomenon. The study showed a significant relationship between insular cortex lesion and ASR in rats.
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http://dx.doi.org/10.1080/00207454.2020.1716751DOI Listing
November 2020

Oxytocin moderates risky decision-making during the Iowa Gambling Task: A new insight based on the role of oxytocin receptor gene polymorphisms and interventional cognitive study.

Neurosci Lett 2019 08 11;708:134328. Epub 2019 Jun 11.

Research Center for Addiction and Risky Behavior (ReCARB), Iran University of Medical Sciences (IUMS), Tehran, Iran. Electronic address:

The oxytocinergic system influences attentional bias towards emotional cues and feedback-based learning. Considering a tag single-nucleotide polymorphism (SNP) found through analysis of an intronic haplotype in the oxytocin receptor (OXTR) gene, we investigated the effect of oxytocin on risky decision-making via the Iowa Gambling Task (IGT). Young healthy males received intranasal oxytocin or placebo, and the IGT was performed where raw scores, net scores and total time were recorded, and ratio of advantageous to disadvantageous choices was calculated. Using PCR-pyrosequencing, a 761 bp target sequence in the OXTR gene was amplified and sequenced after the extraction of whole blood DNA. Employing Haploview, haplotypes and linkage disequilibrium (LD) pattern among all 14 SNPs in the intronic region were determined based on D' and LOD values, and rs2254295 with the highest LD was indicated as the tag SNP. GTT was shown to have the highest frequency among the found haplotypes. Oxytocin group and participants with the TT genotype demonstrated a significantly increased raw score, net score and advantageous choices, whereas the total time was not influenced remarkably. This means that oxytocin significantly reduced the risk taking in decision-making, and participants with the TT genotype had less premature or risky decisions than those with the CT and CC genotypes. rs2254295 may modulate the function or expression of the OXTR gene, implying that T allele may increase the expression of the OXTR gene compared to C allele. We suggest that oxytocin may remarkably moderate the risk attitude and its consequences during uncertain decision-making.
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http://dx.doi.org/10.1016/j.neulet.2019.134328DOI Listing
August 2019

Does 5, 7-Dihydroxytryptamine injection into nucleus accumbens cause hyperacusis?

Neurosci Lett 2019 07 7;705:246-250. Epub 2019 Apr 7.

Tehran University, peach e shemiran, Tehran, Iran.

Hyperacusis may be defined as diminishing tolerance to moderate and high intensity sounds in people with normal hearing sensitivity. Serotonin plays a critical role in some of auditory tasks including startle reflex and prepulse inhibition. Serotonin deficiency can cause some diseases which can coincide with hyperacusis. The aim of the present study was to investigate the probable influence of serotonergic depletion in nucleus accumbens (NAcc) on the startle reflex. The startle reflexes were examined in Wistar rats (n: 48) in different intensities with and without the background noise. The amplitude of startle reflex significantly increased in NAcc-injected rats without background noise, while this difference disappeared in the presence of background noise in all intensities. These data proposed that the injection of 5, 7-Dihydroxytryptamine (5, 7-DHT) into nucleus accumbens will cause hyperacusis-like behavior, and strengthens the possibility of the role of serotonin and nucleus accumbens in hyperacusis.
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http://dx.doi.org/10.1016/j.neulet.2019.01.040DOI Listing
July 2019

Publisher Correction: Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes.

Sci Rep 2018 Nov 29;8(1):17585. Epub 2018 Nov 29.

Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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http://dx.doi.org/10.1038/s41598-018-36220-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6265300PMC
November 2018

Flexible Learning-Free Segmentation and Reconstruction of Neural Volumes.

Sci Rep 2018 09 24;8(1):14247. Epub 2018 Sep 24.

Department of Computer Science and Engineering, University of Notre Dame, Notre Dame, IN, USA.

Imaging is a dominant strategy for data collection in neuroscience, yielding stacks of images that often scale to gigabytes of data for a single experiment. Machine learning algorithms from computer vision can serve as a pair of virtual eyes that tirelessly processes these images, automatically detecting and identifying microstructures. Unlike learning methods, our Flexible Learning-free Reconstruction of Imaged Neural volumes (FLoRIN) pipeline exploits structure-specific contextual clues and requires no training. This approach generalizes across different modalities, including serially-sectioned scanning electron microscopy (sSEM) of genetically labeled and contrast enhanced processes, spectral confocal reflectance (SCoRe) microscopy, and high-energy synchrotron X-ray microtomography (μCT) of large tissue volumes. We deploy the FLoRIN pipeline on newly published and novel mouse datasets, demonstrating the high biological fidelity of the pipeline's reconstructions. FLoRIN reconstructions are of sufficient quality for preliminary biological study, for example examining the distribution and morphology of cells or extracting single axons from functional data. Compared to existing supervised learning methods, FLoRIN is one to two orders of magnitude faster and produces high-quality reconstructions that are tolerant to noise and artifacts, as is shown qualitatively and quantitatively.
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http://dx.doi.org/10.1038/s41598-018-32628-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6155135PMC
September 2018

Corrigendum to "A new rat model of neonatal bilirubin encephalopathy (kernicterus)" [J. Pharmacol. Toxicol. Methods 84 (2017) 44-50].

J Pharmacol Toxicol Methods 2018 Jul - Aug;92:95. Epub 2018 Mar 11.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.vascn.2018.02.006DOI Listing
March 2018

Corrigendum to "A new rat model of neonatal bilirubin encephalopathy (kernicterus)" [J. Pharmacol. Toxicol. Methods 84 (2017) 44-50].

J Pharmacol Toxicol Methods 2018 Jul - Aug;92:95. Epub 2018 Mar 11.

Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran; Bioengineering Research Group, Nanotechnology and Advanced Materials Department, Materials and Energy Research Center (MERC), Tehran, Iran. Electronic address:

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http://dx.doi.org/10.1016/j.vascn.2018.02.006DOI Listing
March 2018

Evaluation of metformin effects in the chronic phase of spontaneous seizures in pilocarpine model of temporal lobe epilepsy.

Metab Brain Dis 2018 02 27;33(1):107-114. Epub 2017 Oct 27.

Cellular and Molecular Research Center, Iran University of Medical Science, Tehran, Iran.

Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy.
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http://dx.doi.org/10.1007/s11011-017-0132-zDOI Listing
February 2018

The Effect of Luteinizing Hormone Reducing Agent on Anxiety and Novel Object Recognition Memory in Gonadectomized Rats.

Basic Clin Neurosci 2017 Mar-Apr;8(2):113-119

Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Mood disorders such as anxiety and depression are common following menopause and andropause. Lack of sex steroid hormones is suggested as the primary cause of these disturbances. The level of luteinizing hormone (LH) would also rise 3-4 times than normal in these people. The potential effects of LH on mood and cognitive symptoms following menopause and andropause are still unknown. This study aimed to investigate the effect of increased LH on novel object discrimination (NOD) memory and anxiety like behavior in gonadectomized rats.

Methods: Four-month-old male and female Wistar rats were randomly assigned into 4 groups (in each sex): control rats (Cont), gonadectomized without treatment (GnX), gonadectomized treated with triptorelin, a GnRH agonist which reduces LH release eventually, (GnX+Tr), gonadectomized treated with triptorelin plus sex steroid hormone, estradiol in female and testosterone in male rats (GnX+Tr+S/T). After 4 weeks treatment, anxiety score (elevated plus maze) and NOD were measured. Data were analyzed using One-way ANOVA, and P-values less than 0.05 were considered as significant.

Results: Gonadectomy increased anxiety like behaviors (decrease of presence time in the open arms) in female rats (P=0.012), but not in male ones (P=0.662). Additionally, triptorelin alone reduced the increased anxiety score in gonadectomized female rats, compared to group treated with both triptorelin and estradiol. Furthermore, it was shown that gonadectomy and or treatment with triptorelin and sex steroids had no significant effect on novel object recognition memory in both female (P=0.472) and male rats (P=0.798).

Conclusion: Findings of this study revealed that increased level of LH following menopause or andropause should be considered as a possible cause for increased anxiety. Also, this study showed that LH reducing agents would reduce anxiety like behavior in gonadectomized female rats. The effect of increased LH on cognitive functions such as novel object recognition memory was not evident in this study and needs further studies.
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http://dx.doi.org/10.18869/nirp.bcn.8.2.113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5440920PMC
May 2017

Neuroprotective Effects of Exercise on Brain Edema and Neurological Movement Disorders Following the Cerebral Ischemia and Reperfusion in Rats.

Basic Clin Neurosci 2017 Jan;8(1):77-84

Department of Neuroscience, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Cerebral ischemia and reperfusion causes physiological and biochemical changes in the neuronal cells that will eventually lead to cell damage. Evidence indicates that exercise reduces the ischemia and reperfusion-induced brain damages in animal models of stroke. In the present study, the effect of exercise preconditioning on brain edema and neurological movement disorders following the cerebral ischemia and reperfusion in rats was investigated.

Methods: Twenty-one adult male wistar rats (weighing 260-300 g) were randomly divided into three groups: sham operated, exercise plus ischemia, and ischemia group (7 rats per group). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Transient focal cerebral ischemia and reperfusion were induced by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by reperfusion for 23 hours. After 24 hours ischemia, movement disorders were tested by a special neurological examination. Also, cerebral edema was assessed by determining the brain water content.

Results: The results showed that pre-ischemic exercise significantly reduced brain edema (P<0.05). In addition, exercise preconditioning decreased the neurological movement disorders caused by brain ischemia and reperfusion (P<0.05).

Conclusion: Preconditioning by exercise had neuroprotective effects against brain ischemia and reperfusion-induced edema and movement disorders. Thus, it could be considered as a useful strategy for prevention of ischemic injuries, especially in people at risk.
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http://dx.doi.org/10.15412/J.BCN.03080110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395689PMC
January 2017

Effect of bumetanide, a selective NKCC1 inhibitor, on hallucinations of schizophrenic patients; a double-blind randomized clinical trial.

Schizophr Res 2017 06 9;184:145-146. Epub 2016 Dec 9.

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

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http://dx.doi.org/10.1016/j.schres.2016.12.002DOI Listing
June 2017

Lack of the effect of bumetanide, a selective NKCC1 inhibitor, in patients with schizophrenia: A double-blind randomized trial.

Psychiatry Clin Neurosci 2017 Jan 21;71(1):72-73. Epub 2016 Dec 21.

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

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http://dx.doi.org/10.1111/pcn.12475DOI Listing
January 2017

A new rat model of neonatal bilirubin encephalopathy (kernicterus).

J Pharmacol Toxicol Methods 2017 Mar - Apr;84:44-50. Epub 2016 Oct 13.

Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Neuroscience Department, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Introduction: Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin.

Methods: For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively.

Result: The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs.

Conclusion: This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies.
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http://dx.doi.org/10.1016/j.vascn.2016.10.002DOI Listing
July 2017

Reconstruction of genetically identified neurons imaged by serial-section electron microscopy.

Elife 2016 07 7;5. Epub 2016 Jul 7.

Center for Brain Science, Harvard University, Cambridge, United States.

Resolving patterns of synaptic connectivity in neural circuits currently requires serial section electron microscopy. However, complete circuit reconstruction is prohibitively slow and may not be necessary for many purposes such as comparing neuronal structure and connectivity among multiple animals. Here, we present an alternative strategy, targeted reconstruction of specific neuronal types. We used viral vectors to deliver peroxidase derivatives, which catalyze production of an electron-dense tracer, to genetically identify neurons, and developed a protocol that enhances the electron-density of the labeled cells while retaining the quality of the ultrastructure. The high contrast of the marked neurons enabled two innovations that speed data acquisition: targeted high-resolution reimaging of regions selected from rapidly-acquired lower resolution reconstruction, and an unsupervised segmentation algorithm. This pipeline reduces imaging and reconstruction times by two orders of magnitude, facilitating directed inquiry of circuit motifs.
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http://dx.doi.org/10.7554/eLife.15015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4959841PMC
July 2016

Protection of Hippocampal CA1 Neurons Against Ischemia/Reperfusion Injury by Exercise Preconditioning via Modulation of Bax/Bcl-2 Ratio and Prevention of Caspase-3 Activation.

Basic Clin Neurosci 2016 Jan;7(1):21-9

Department of Neuroscience, Faculty of Advanced Technologies in Medical Sciences, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Ischemia leads to loss of neurons by apoptosis in specific brain regions, especially in the hippocampus. The purpose of this study was investigating the effects of exercise preconditioning on expression of Bax, Bcl-2, and caspase-3 proteins in hippocampal CA1 neurons after induction of cerebral ischemia.

Methods: Male rats weighing 260-300 g were randomly allocated into three groups (sham, exercise, and ischemia). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Ischemia was induced by the occlusion of both common carotid arteries (CCAs) for 20 min. Levels of expression of Bax, Bcl-2, and caspase-3 proteins in CA1 area of hippocampus were determined by immunohistochemical staining .

Results: The number of active caspase-3-positive neurons in CA1 area were significantly increased in ischemia group, compared to sham-operated group (P<0.001), and exercise preconditioning significantly reduced the ischemia/reperfusion-induced caspase-3 activation, compared to the ischemia group (P<0.05). Also, results indicated a significant increase in Bax/Bcl-2 ratio in ischemia group, compared to sham-operated group (P<0.001).

Discussion: This study indicated that exercise has a neuroprotective effects against cerebral ischemia when used as preconditioning stimuli.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892327PMC
January 2016

Imported lymphatic filariasis in an Indian immigrant to iran.

Iran J Parasitol 2014 Mar;9(1):145-8

Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Lymphatic filariasis (LF), a nematode disease transmitted by arthropod vectors, is repeatedly reported in immigrant population. This disease is not endemic in Iran; however, different species of mosquitoes, capable of transmission of parasite microfilaria, are distributed in the country. Hereby, incidental detection of an imported case of LF due to Wuchereria bancrofti in an Indian worker in Iran is reported. Identification of the case was performed based on morphological and morphometrical characteristics of microfilaria and PCR sequencing.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4289875PMC
March 2014

Anticonvulsant activity of the ethanolic extract of Punica granatum L. seed.

Neurol Res 2015 Jun 21;37(6):470-5. Epub 2014 Nov 21.

Objective: Various morphological parts of pomegranate (Punica granatum L.) have extensively been used in the folk medicine to treat an array of human ailments. The aim of the present study is to demonstrate the anticonvulsant potential of the ethanolic extract of P. granatum L. seed in chemoconvulsant-induced seizures in mice.

Method: The anticonvulsant activity of the ethanolic extract was investigated in strychnine (STR)-induced and pentylenetetrazole (PTZ)-induced seizure models in mice. Diazepam was used as reference anticonvulsant drug. Ethanolic extract (150, 300, and 600 mg/kg per os, p.o.), diazepam (1 mg/kg intraperitoneally, i.p.), and distilled water (10 ml/kg, i.p.) were administered before induction of seizures by PTZ (60 mg/kg, i.p.) or STR (2.5 mg/kg, i.p.). The latent time before the onset of convulsions, the duration of convulsions, the percentage of seizure protection, and mortality rate were recorded.

Results: The seed ethanolic extract did not show any toxicity and did not protect the animals against seizures but demonstrated a significant increase in seizure latency at 300 and 600 mg/kg in both STR and PTZ seizure models (P < 0.001). It also showed a significant reduction in seizure duration at 300 mg/kg (P < 0.05) and 600 mg/kg (P < 0.001) in the STR seizure model and 600 mg/kg (P < 0.01) in the PTZ seizure model compared with the control group.

Conclusion: Ethanol extract has dose-dependent anticonvulsant activity against STR- and PTZ-induced seizures. This activity might be due to its saponins, flavonoids, triterpenes, and alkaloids ingredients.
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http://dx.doi.org/10.1179/1743132814Y.0000000460DOI Listing
June 2015

Human erythropoietin effect in postoperative visual loss following spine surgery: a case report.

Anesth Pain Med 2014 May 6;4(2):e7291. Epub 2014 Apr 6.

Physiology Research Center (PRC), Iran University of Medical Sciences, Tehran, Iran.

Introduction: Postoperative visual loss (POVL) has become the focus of attention for anesthesiologists as a hallmark of perioperative management in spine surgery. A number of Intraoperative and postoperative factors has been documented but the exact etiology is still unclear. Nowadays, perioperative management and also complete curing of POLV is a big question of ophthalmologists and anesthesiologists. The purpose of this case report is to present a unique experience of complete curing the POLV.

Case Presentation: Our patient was a 61-year-old man, with 75 kg weight and 180 cm height. The patient had no history of visual impairment except mild cataract in his right eye. The patient had a history of diffuse idiopathic skeletal hyperostosis (DISH). The patient had undergone lumbar surgery in prone position. The operation time was about 6 hours. About 30 minutes after transferring to postanesthesia care unit (PACU), patient was awake and complained of losing his eyesight. There was no vision and light perception in his right eye on primary examination. Urgent ophthalmologist consultation was requested. In ophthalmology examinations, the pupil reflex to light was absent in the right eye. After obtaining patients and his family informed consent, four hours after the operation, 40000 I.U. of recombinant human erythropoietin (rhEPO) was administered for patient in PACU (IV infusion, in 30 min). An ophthalmologist visited him every 6 hours after administration of rhEPO. The patient was transferred to intensive care unit (ICU) one hour later with total visual loss in the right eye. Ophthalmologic examination after the second dose of rhEPO, 30 hours after the operation, reported pupil reflex enhancement and light perception in his right eye. Finally the third dose of rhEPO (40000 I.U., IV infusion) was administered on the third day. Ophthalmologic examination after the third dose of rhEPO, 60 hours after the operation, reported normal pupillary light reflex of the right eye and visual acuity improvement to 20/20. The patient was discharged from hospital after six days, with normal visual acuity and without any new complications except surgical site pain.

Conclusions: Our case report showed the therapeutic effect of rhEPO in complete curing of POVL. Regarding the side effects of EPO such as thrombogenic effects or mild hemodynamic changes like transient sinus tachycardia during infusion, it seems that beneficial effects of EPO is more than its disadvantages and expenses, for patients with POVL.
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http://dx.doi.org/10.5812/aapm.7291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997951PMC
May 2014

Automatic bolus tracking versus fixed time-delay technique in biphasic multidetector computed tomography of the abdomen.

Iran J Radiol 2014 Jan 30;11(1):e4617. Epub 2014 Jan 30.

Department of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran.

Background: Bolus tracking can individualize time delay for the start of scans in spiral computed tomography (CT).

Objectives: We compared automatic bolus tracking method with fixed time-delay technique in biphasic contrast enhancement during multidetector CT of abdomen.

Patients And Methods: Adult patients referred for spiral CT of the abdomen were randomized into two groups; in group 1, the arterial and portal phases of spiral scans were started 25 s and 55 s after the start of contrast material administration; in group 2, using the automatic bolus tracking software, repetitive monitoring scans were performed within the lumen of the descending aorta as the region of interest with the threshold of starting the diagnostic scans as 60 HU. The contrast enhancement of the aorta, liver, and spleen were compared between the groups.

Results: Forty-eight patients (23 males, 25 females, mean age=56.4±13.5 years) were included. The contrast enhancement of the aorta, liver, and spleen at the arterial phase was similar between the two groups (P>0.05). Regarding the portal phase, the aorta and spleen were more enhanced in the bolus-tracking group (P<0.001). The bolus tracking provided more homogeneous contrast enhancement among different patients than the fixed time-delay technique in the liver at portal phase, but not at the arterial phase.

Conclusions: The automatic bolus-tracking method, results in higher contrast enhancement of the aorta and spleen at the portal phase, but has no effect on liver enhancement. However, bolus tracking is associated with reduced variability for liver enhancement among different patients.
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http://dx.doi.org/10.5812/iranjradiol.4617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955856PMC
January 2014

The effect of leptin on prepulse inhibition in a developmental model of schizophrenia.

Neurosci Lett 2013 Oct 20;555:57-61. Epub 2013 Sep 20.

Physiology Research Center, and Physiology Department, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Post-weaning social isolation is a developmental animal model of schizophrenia. Impairment of prepulse inhibition (PPI), possibly due to increased activity of the mesolimbic dopaminergic system, has frequently been reported in this model. There are some reports of increased level of leptin in schizophrenic patients. It has been shown that intracerebroventricular (ICV) injection of leptin decreases dopamine in the nucleus accumbens of rats. Here we investigated the effect of leptin on PPI impairment following social isolation. Five groups of Sprague-Dawley rats were reared post weaning in social or isolated conditions for 14 weeks. PPI was measured before treatment in week 12, and after ICV injection of vehicle or different doses of leptin (1, 5, and 10μg/5μl) in week 14. Results showed reduced PPI in untreated isolated compared to socially-reared rats in week 12 (p=0.009), but not in week 14 (p=0.45). Results also showed that leptin dose-dependently increased the basal PPI in isolated rats compared to vehicle, that was significant at a dose of 10μg (p=0.002). A considerable but non-significant effect of treatment with leptin on startle response (p=0.13) was seen. In conclusion, our results reveal that leptin significantly increases PPI in socially-isolated rats. The findings of this study suggest possible antipsychotic properties for leptin. We suggest further studies on the possible disruption of leptin signaling in schizophrenia, and also the possible interaction of leptin with therapeutic effects of second generation antipsychotics.
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http://dx.doi.org/10.1016/j.neulet.2013.09.027DOI Listing
October 2013

Chronic Ritalin administration during adulthood increases serotonin pool in rat medial frontal cortex.

Iran Biomed J 2013 ;17(3):134-9

Biotechnology Research Center, Dept. of Medical Biotechnology, Venom and Toxin Unit, Pasteur Institute of Iran, Tehran, Iran.

Background: Ritalin has high tendency to be abused. It has been the main indication to control attention deficit hyperactivity disorder. The college students may seek for it to improve their memory, decrease the need for sleep (especially during exams), which at least partially, can be related to serotonergic system. Therefore, it seems worthy to evaluate the effect of Ritalin intake on mature brain. There are many studies on Ritalin effect on developing brain, but only few studies on adults are available. This study was undertaken to find Ritalin effect on serotonin transporter (SERT) density in medial frontal cortex (MFC) of mature rat.

Methods: Thirty male Wistar rats were used in the study. Rats were assigned into five groups (n = 6 per group): one control, two Ritalin and two vehicle groups. Twelve rats received Ritalin (20 mg/kg/twice a day) orally for eleven continuous days. After one week of withdrawal and another two weeks of rest, in order to evaluate short-term effects of Ritalin, six rats were sacrificed. Another six rats were studied to detect the long-term effects of Ritalin; therefore, they were sacrificed 12 weeks after the previous group. The immunohistochemistry was performed to evaluate the results.

Results: Immunohistochemistry studies showed a higher density of SERT in both 2 and 12 weeks after withdrawal from Ritalin intake in MFC of rat and there was no significant difference between these two groups.

Conclusions: Our findings demonstrated both short- and long-term effects of Ritalin on frontal serotonergic system after withdrawal period.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770255PMC
http://dx.doi.org/10.6091/ibj.1173.2013DOI Listing
April 2014

Cell therapy in spinal cord injury: a mini- reivew.

Basic Clin Neurosci 2013 ;4(2):172-6

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

Spinal cord injury (SCI) is a debilitating disease which leads to progressive functional damages. Because of limited axonal regeneration in the central nervous system, there is no or little recovery expected in the patients. Different cellular and molecular approaches were investigated in SCI animal models. Cellular transplantation of stem cells can potentially replace damaged tissue and provide a suitable microenvironment for axons to regenerate. Here, we reviewed the last approaches applied by our colleagues and others in order to improve axonal regeneration following SCI. We used different types of stem cells via different methods. First, fetal olfactory mucosa, schwann, and bone marrow stromal cells were transplanted into the injury sites in SCI models. In later studies, was applied simultaneous transplantation of stem cells with chondroitinase ABC in SCI models with the aid of nanoparticles. Using these approaches, considerable functional recovery was observed. However, considering some challenges in stem cell therapy such as rejection, infection, and development of a new cancer, our more recent strategy was application of cytokines. We observed a significant improvement in motor function of rats when stromal derived factor-1 was used to attract innate stem cells to the injury site. In conclusion, it seems that co-transplantation of different cells accompanies with other factors like enzymes and growth factors via new delivery systems may yield better results in SCI.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202537PMC
October 2014