المؤلفون: Parsa Gholipour, Zahra Ebrahimi, Reihaneh Mohammadkhani, Reza Ghahremani, Iraj Salehi, Abdolrahman Sarihi, Alireza Komaki, Seyed Asaad Karimi

المصدر: Scientific Reports, Vol 14, Iss 1, Pp 1-9 (2024)

مصطلحات موضوعية: Autism spectrum disorder, Valproic acid, Long-term potentiation, mGlu8 receptor, Hippocampus, Medicine, Science

الوصف: Abstract Autism spectrum disorder (ASD) is a pervasive neurodevelopmental condition characterized by social interaction deficits, communication impairments, repetitive behaviors, and sensory sensitivities. While the etiology of ASD is multifaceted, abnormalities in glutamatergic neurotransmission and synaptic plasticity have been implicated. This study investigated the role of metabotropic glutamate receptor 8 (mGlu8) in modulating long-term potentiation (LTP) in a rat model of ASD induced by prenatal valproic acid (VPA) exposure. To induce an animal model with autism-like characteristics, pregnant rats received an intraperitoneal injection of 500 mg/kg of sodium valproate (NaVPA) on embryonic day 12.5. High-frequency stimulation was applied to the perforant path-dentate gyrus (PP-DG) synapse to induce LTP, while the mGlu8 receptor agonist (S)-3,4-dicarboxyphenylglycine (DCPG) was administered into the DG. The results revealed that VPA-exposed rats exhibited reduced LTP compared to controls. DCPG had contrasting effects, inhibiting LTP in controls and enhancing it in VPA-exposed rats. Moreover, reduced social novelty preference index (SNPI) in VPA-exposed rats was reversed by intra-DG administration of S-3,4-DCPG. In conclusion, our study advances our understanding of the complex relationship between glutamatergic neurotransmission, synaptic plasticity, and VPA-induced autism model. The findings suggest that mGlu8 receptor dysfunction plays a role in the impaired synaptic plasticity seen in ASD.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/a5dc1a7d638a4d56804d8c2d95fc4455Test

المؤلفون: Zahra Ebrahimi, Parsa Gholipour, Reihaneh Mohammadkhani, Reza Ghahremani, Abdolrahman Sarihi, Alireza Komaki, Iraj Salehi, Seyed Asaad Karimi

المصدر: IBRO Neuroscience Reports, Vol 16, Iss , Pp 629-634 (2024)

مصطلحات موضوعية: Autism Spectrum Disorder, MGlu4 receptors, VU0155041, Long-term potentiation, Valproic acid, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: The precise cause of autism spectrum disorder (ASD) is not fully understood. Despite the involvement of glutamatergic dysregulation in autism, the specific contribution of mGlu4 receptors to synaptic plasticity remains unclear. Using the positive allosteric modulator VU0155041, we aimed to restore long-term potentiation (LTP) in the perforant path-dentate gyrus (PP-DG) pathway in VPA-induced autistic rat model. High-frequency stimulation was applied to the PP-DG synapse to induce LTP, while the VU0155041 was administered into the DG. Unexpectedly, VU0155041 failed to alleviate the observed LTP reduction in VPA-exposed rats, further resulting in a significant decrease in population spike LTP. This unexpected outcome prompts discussion on the complex nature of mGlu4 receptor modulation, highlighting potential interference with physiological processes underlying synaptic plasticity.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2667242124000502Test; https://doaj.org/toc/2667-2421Test

الوصول الحر: https://doaj.org/article/ee1200eddb6b46e0bb83a571cee34132Test

المؤلفون: Farshid Mohammadi, Mehta Razzaghi, Seyed Saman Talebi, Salman Khazaei, Seyed Asaad Karimi

المصدر: پزشکی بالینی ابن سینا, Vol 30, Iss 3, Pp 173-178 (2023)

مصطلحات موضوعية: anti-beta 2 glycoprotein antibody, anti-cardiolipin antibody, anti-glycoprotein antibody, anti-phospholipid antibody, covid-19, Medicine

الوصف: Background and Objective: COVID-19 disease has various manifestations, such as fever, sore throat, shortness of breath, body pain, and loss of consciousness. This disease may cause coagulation disorders and therefore an increase in thromboembolic events in these patients. This study examines the status of anti-phospholipid antibodies (aPL) in such patients, as one of the factors of increased coagulability. Materials and Methods: This case-control study examined anti-phospholipid antibodies (including lupus anticoagulant, anti-cardiolipin antibody, and anti-beta-2 glycoprotein antibody) in 60 patients with definite mild COVID-19. Patients were included in the study if they met the inclusion criteria. The blood samples of the studied subjects were analyzed in the unit's laboratory. The patients' sample results were compared to those of 60 healthy individuals who were matched in terms of age and gender. Results: The mean age scores of the case and control groups were 48.54±15.29 and 46.91±16.71 years, respectively (P=0.57). In case group, the Anti-β2GPI (IgG and IgM) test was positive in two patients (P=0.578 and P=0.346). The LAC test was positive in 3 patients and 2 controls (P=0.57). Anti-cardiolipin antibodies was positive in 4 patients (IgG in 1 patient and IgM in 3 patients), compared to the control group in 1 patient (P=0.004). Conclusion: According to the results of this study, the prevalence of aPL was higher in patients with mild COVID-19 than in healthy individuals. Considering the role of aPL in thrombosis, it may increase the coagulability conditions in these patients.

وصف الملف: electronic resource

العلاقة: http://sjh.umsha.ac.ir/article-1-2832-en.pdfTest; https://doaj.org/toc/2588-722XTest; https://doaj.org/toc/2588-7238Test

الوصول الحر: https://doaj.org/article/2e532708afbc485ea015a1707246ed16Test

المؤلفون: Nazanin Hatami Bavarsad, Leila Jahangard, Masood Saidijam, Seyed Asaad Karimi, Ali Reza Soltanian, Elahe Shahriari, Saeid Afshar, Abdolrahman Sarihi

المصدر: Cell Journal, Vol 25, Iss 11, Pp 783-789 (2023)

مصطلحات موضوعية: borderline personality disorder, monoacylglycerol lipase, polymorphism, Medicine, Science

الوصف: Objective: From the perspective of etiology, borderline personality disorder (BPD) is a multifactorial and complexdisorder, hence our understanding about the molecular basis and signaling of this disorder is extremely limited.The purpose of this study was evaluating the relationship between BPD and the Monoacylglycerol lipase (MGLL)polymorphism rs782440 in the population of Hamadan, Iran.Materials and Methods: In this case-control study, 106 participants including 53 patients with BPD and 53healthy control subjects were selected by psychiatrists in the Department of Psychiatry at Farshchian SinaHospital in Hamadan. The BPD patients were selected based on the Diagnostic and Statistical Manual of MentalDisorders (DSM-5) form for diagnosing BPD patients. For genotyping, polymerase chain reaction (PCR) wasused to amplify the desired region including the MGLL intronic C>T single nucleotide polymorphism (SNP)(rs782440) and afterward the amplicon was sequenced using the Sanger sequencing method. To determine thegenotype of these patients, their sequences were aligned with the reference sequence of MGLL through the CLCgenomic workbench software.Results: The results indicated that the frequency of TT in comparison to the CC genotype was significantly different(P=0.003) and the risk of BPD in change from the TT genotype to CC genotype was increased by 6.679%. Regardingthe frequency of allele in this group, no significant difference was observed.Conclusion: This paper, has studied and reports for the first time, the association between MGLL SNP (rs782440) withBPD. The findings of the current research revealed that the TT genotype increases the risk of BPD compared to the CCgenotype. Considering the lack of a suitable diagnostic biomarker for BPD, using this potential biomarker in the nearfuture can be promising.

وصف الملف: electronic resource

العلاقة: https://www.celljournal.org/article_708185_db36c79cdcc65741ebd39b4cf673ca0c.pdfTest; https://doaj.org/toc/2228-5806Test; https://doaj.org/toc/2228-5814Test

الوصول الحر: https://doaj.org/article/0518b385d25842f1b9eff19daed47ce0Test

المؤلفون: Seyed Asaad Karimi, Fatama Tuz Zahra, Loren J. Martin

المصدر: Pharmacological Research, Vol 200, Iss , Pp 107073- (2024)

مصطلحات موضوعية: Pain, Preclinical, Translational, Drug discovery, Mouse, Rat, Therapeutics. Pharmacology, RM1-950

الوصف: Chronic pain is a complex and challenging medical condition that affects millions of people worldwide. Understanding the underlying mechanisms of chronic pain is a key goal of preclinical pain research so that more effective treatment strategies can be developed. In this review, we explore nociception, pain, and the multifaceted factors that lead to chronic pain by focusing on preclinical models. We provide a detailed look into inflammatory and neuropathic pain models and discuss the most used animal models for studying the mechanisms behind these conditions. Additionally, we emphasize the vital role of these preclinical models in developing new pain-relief drugs, focusing on biologics and the therapeutic potential of NMDA and cannabinoid receptor antagonists. We also discuss the challenges of TRPV1 modulation for pain treatment, the clinical failures of neurokinin (NK)− 1 receptor antagonists, and the partial success story of Ziconotide to provide valuable lessons for preclinical pain models. Finally, we highlight the overall success and limitations of current treatments for chronic pain while providing critical insights into the development of more effective therapies to alleviate the burden of chronic pain.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S1043661824000173Test; https://doaj.org/toc/1096-1186Test

الوصول الحر: https://doaj.org/article/eec57e221ca1487fa27ee961e46cd8f1Test

المؤلفون: Masoumeh Nazari, Seyed Asaad Karimi, Somayeh Komaki, Masoumeh Kourosh Arami, Alireza Komaki

المصدر: BMC Neuroscience, Vol 24, Iss 1, Pp 1-10 (2023)

مصطلحات موضوعية: Hippocampus, Paired-pulse ratio, Cannabinoid CB1 receptors, GABAB receptors, Long-term Potentiation, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495

الوصف: Abstract Background The release of various neurotransmitters and thereby the excitability of neuronal circuits are regulated by the endocannabinoid system in an activity-dependent manner. Hippocampal long-term potentiation (LTP) is augmented in cannabinoid type 1 (CB1) receptor-deficient mice. CB1 receptors exist on GABAergic axon terminals in the hippocampus. In our previous work, we showed that CB1 antagonists increased the population spike (PS) amplitude, field excitatory post-synaptic potential (fEPSP), and the LTP induction in the dentate gyrus (DG) of the rat hippocampus while the GABAB antagonist decreased these parameters. Determining the underlying mechanisms of the pre- and/or postsynaptic locus of LTP expression is of great importance. In this study, we investigated whether LTP alteration acutely caused by CB1 and GABAB receptor antagonists (AM251 and CGP55845, respectively) happens at the postsynaptic or presynaptic regions, or at both. Therefore, the paired-pulse ratio (PPR) was assessed prior to and following the LTP induction in the studied groups. Methods Male Wistar rats were randomly assigned to the groups of control, AM251, CGP55845, CGP55845 + AM251. A high-frequency stimulation (HFS) of the perforant path (PP) was used to induce LTP in the DG region. Results Statistical analysis revealed that AM251 produced significant increase in excitatory postsynaptic potential (EPSP) slope and amplitude of PS. Conversely, administration of CGP55845 produced decrease in slope of EPSP. The current results indicated that the PPR was not influenced by LTP induction in the presence of AM251 or CGP55845 either alone or their combination. Conclusions It can be concluded that the site causing LTP expression is, at least in part, the postsynaptic site because PPR was not influenced by LTP induction in the presence of AM251 or CGP55845 either alone or their combination.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2202Test

الوصول الحر: https://doaj.org/article/aeb74abe7cd844e69ef6cc2f2dd35f27Test

المؤلفون: Reihaneh Mohammadkhani, Alireza Komaki, Seyed Asaad Karimi, Mahdi Behzad, Shirin Heidarisasan, Iraj Salehi

المصدر: Frontiers in Physiology, Vol 14 (2023)

مصطلحات موضوعية: maternal exercise, offspring, high-intensity interval training, mitochondrial gene expression, oxidant-antioxidant status, elevated plus-maze, Physiology, QP1-981

الوصف: Considerable scientific evidence suggests that the intrauterine environment plays a crucial role in determining the long-term health of offspring. The present study aims to investigate the effects of high-intensity interval training in maternal rats before and during pregnancy on the antioxidant status, mitochondrial gene expression, and anxiety-like behavior of their offspring. A total of thirty-two female rats were assigned to four maternal groups based on the timing of exercise: before pregnancy, before and during pregnancy, during pregnancy, and sedentary. The female and male offspring were allocated to groups that matched their mothers’ exercise regimen. Anxiety-like behavior in the offspring was evaluated using the open-field and elevated plus-maze tests. Our findings indicate that maternal HIIT does not have any detrimental effect on the anxiety-related behavior of offspring. Also, maternal exercise before and during pregnancy could improve the general activity of the offspring. Furthermore, our results demonstrate that female offspring exhibit more locomotion activity than males. Besides, maternal HIIT leads to a reduction in the levels of TOS and MDA, while TAC levels increase, and significantly upregulate the gene expression of PGC1-α, NFR1, and NRF2 in both sexes in the heart. Therefore, our study suggests that maternal HIIT is a beneficial maternal behavior and serves as a cardioprotective agent to enhance the health of the next generations.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphys.2023.1117666/fullTest; https://doaj.org/toc/1664-042XTest

الوصول الحر: https://doaj.org/article/aaa3241346634445a614b005285f81e8Test

المؤلفون: Samaneh Safari, Nesa Ahmadi, Reihaneh Mohammadkhani, Reza Ghahremani, Maryam Khajvand-Abedeni, Siamak Shahidi, Alireza Komaki, Iraj Salehi, Seyed Asaad Karimi

المصدر: Behavioral and Brain Functions, Vol 17, Iss 1, Pp 1-11 (2021)

مصطلحات موضوعية: Long-term potentiation, Hippocampus, Dentate Gyrus, Spatial learning and memory, Sex difference, Wistar Rat, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Background Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. Results In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Conclusions Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1744-9081Test

الوصول الحر: https://doaj.org/article/3ca4165055c1474a8215b940243de302Test

المؤلفون: Zahra Ebrahimi, Nazanin Kahvandi, Alireza Komaki, Seyed Asaad Karimi, Marzieh Naderishahab, Abdolrahman Sarihi

المصدر: BMC Neuroscience, Vol 22, Iss 1, Pp 1-10 (2021)

مصطلحات موضوعية: Metabotropic glutamate receptor type 4, Nucleus accumbens, Conditioned place preference, Morphine, Rat, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurophysiology and neuropsychology, QP351-495

الوصف: Abstract Background Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). In addition, metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats was investigated. The animals were bilaterally implanted with guide cannulae above the NAc. In the first step of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the second step of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test in order to check the effect of VU0155041 on the expression of morphine-induced CPP. Results The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression. Conclusions The data indicated that intra-NAc administration of VU0155041 dose dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine. These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2202Test

الوصول الحر: https://doaj.org/article/fe58af9f164a440991ffd186ffa90fe7Test

المؤلفون: Nazanin Kahvandi, Zahra Ebrahimi, Seyed Asaad Karimi, Siamak Shahidi, Iraj Salehi, Marzieh Naderishahab, Abdolrahman Sarihi

المصدر: Behavioral and Brain Functions, Vol 17, Iss 1, Pp 1-10 (2021)

مصطلحات موضوعية: Metabotropic glutamate receptor type 8, Nucleus accumbens, Conditioned place preference, Morphine, Rat, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Background The nucleus accumbens (NAc) plays a principal role in drug reward. It has been reported that metabotropic glutamate receptors (mGlu receptors) play a key role in the rewarding pathway(s). Previous studies have shown the vast allocation of the different types of mGlu receptors, including mGlu8 receptors, in regions that are associated with opioid rewards, such as the NAc. The aim of the present study was to evaluate the role of mGlu8 receptors within the NAc in the acquisition and expression phases of morphine induced conditioned place preference (CPP). Adult male Wistar rats were bilaterally implanted by two cannulas' in the NAc and were evaluated in a CPP paradigm. Selective mGlu8 receptor allosteric agonist (S-3,4-DCPG) was administered at doses of 0.03, 0.3, and 3 μg/0.5 μL saline per side into the NAc on both sides during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase, or before place preference test, or post-conditioning (expression) phase of morphine-induced CPP. Results The results revealed that intra-accumbal administration of S-3,4-DCPG (0.3 and 3 μg) markedly decreased the acquisition in a dose-dependent manner but had no effect on expression of morphine-induced CPP. Conclusions The findings suggest that activation of mGlu8 receptors in the NAc dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine which may be related to the glutamate activity into the NAc and in reward pathway(s). These data suggest that mGlu8 receptor may be involved in conditioned morphine reward.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1744-9081Test

الوصول الحر: https://doaj.org/article/7712f8f779304801bd3ce91208f2302aTest