Publications by authors named "Alireza Komaki"

127 Publications

Effects of vanillic acid on Aβ-induced oxidative stress and learning and memory deficit in male rats.

Brain Res Bull 2021 Feb 27. Epub 2021 Feb 27.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Biology, Faculty of Basic Sciences, Bu-Ali Sina University, Hamadan, Iran. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disease, in which the accumulation of β-amyloid (Aβ) peptide in the extracellular space causes a progressive reduction in cognitive performance. Aβ stimulates active oxygen species generation leading to oxidative stress and neural cell death. Vanillic Acid (VA) is the oxidant form of vanillin widely found in vanilla beans. VA has many properties, such as suppressing apoptosis and eliminating the harmful effects of oxidative stress in animal models. The VA effects on impaired learning and memory in Aβ rats were assessed. Forty adults male Wistar rats were assigned to the following five groups in random: the control, sham (received saline (vehicle) via intracerebroventricular (ICV) injection), Aβ (received Aβ1-40 via ICV injection), VA (50 mg/kg by oral gavage once a day through four weeks), and Aβ + VA (50 mg/kg) groups. Open field test, novel object recognition (NOR) test, Morris water maze (MWM) test, and passive avoidance learning (PAL) task were performed, and finally, we determined the malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidant status (TOS) levels. Aβ decreased the cognitive memory in NOR, spatial memory in MWM, and passive avoidance memory in PAL tests. In contrast, VA improved learning and memory in the treated group. Aβ significantly increased MDA and TOS and decreased TAC levels, whereas VA treatment significantly reversed TAC, TOS and MDA levels. In conclusion, VA decreased the Aβ effects on learning and memory by suppressing oxidative stress and can be regarded as a neuroprotective substance in AD.
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http://dx.doi.org/10.1016/j.brainresbull.2021.02.024DOI Listing
February 2021

Vanillic acid attenuates amyloid β1-40-induced long-term potentiation deficit in male rats: an in vivo investigation.

Neurol Res 2021 Feb 24:1-8. Epub 2021 Feb 24.

Department of Animal Sciences and Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.

: Alzheimer disease (AD) is a neurodegenerative disorderliness that involves deductible progressive cognition function caused by amyloid-beta (Aβ) peptide accumulation in the interstitial space. The increase of Aβ stimulates all kinds of active oxygen and causes oxidative stress and apoptosis. In this investigation, we researched the neuroprotective impacts of vanillic acid (VA) on the Aβ-induced (Aβ1-40) long-term potentiation (LTP) of the hippocampus - a commonly probed synaptic plasticity model that happens at the same time as memory and learning - in the AD rats.: Forty-five male Wistar rats were categorized into five groups (n = 8 rats/group, 200-220 g), and studied as control (standard diet), sham (vehicle), VA (50 mg/kg), Aβ and Aβ + VA (50 mg/kg) groups. electrophysiological recordings were implemented after the stereotaxic surgery to gauge the excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the dentate gyrus of the hippocampus. By the stimulation at high-frequency of the perforate pathway, long-term potentiation (LTP) was induced. To assess the plasma levels of malondialdehyde (MDA) and total thiol group (TTG), blood samples were garnered.: In the Aβ-injected rats, EPSP slope, and PS amplitude were significantly reduced after the induction of LTP. Thus, the findings demonstrate that VA decreases the impacts of Aβ on LTP; also, the treatments through VA neuroprotective against the negative effects of Aβ on the synaptic plasticity of the hippocampus can decrease the MDA levels and also increase the TTG levels significantly.: Therefore, based on this experiment on male rats, VA has neuroprotective effects and antioxidants benefits against the Aβ-mediated inhibition of long-term potentiation.
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http://dx.doi.org/10.1080/01616412.2021.1893565DOI Listing
February 2021

A Single Nucleotide Polymorphism Within Molybdenum Cofactor Sulfurase Gene Is Associated With Neuropsychiatric Conditions.

Front Mol Biosci 2020 24;7:540375. Epub 2020 Sep 24.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Molybdenum cofactor sulfurase (MOCOS) is an enzyme participating in purine metabolism. The aim of current study was to evaluate the role of a single nucleotide polymorphism (SNP) in the coding gene (rs594445) in mood disorders and methamphetamine addiction.

Methods: This SNP was genotyped in 200 persons with methamphetamine addiction, 85 patients with bipolar disorder 1 (BP1), 78 patients with BP2, 33 patients with major depressive disorder (MDD) and 200 age-/sex-matched normal subjects using the tetra-primer amplification-refractory mutation system (ARMS)-PCR technique.

Results: The rs594445 was associated with methamphetamine addiction in co-dominant model [A/A vs C/C: OR (95% CI) = 0.466 (0.252-0.864), -value = 0.014; C/A vs C/C: OR (95% CI) = 0.641 (0.418-0.981), -value = 0.04]. This SNP was also associated with this trait in dominant model [OR (95% CI) = 0.591 (0.398-0.879), -value = 0.009]. The A allele of rs594445 had a protective role against methamphetamine addiction [A vs C: OR (95% CI) = 0.645 (0.48-0.866), -value = 0.004]. The rs594445 was associated with BP1 in co-dominant model [C/A vs C/C: OR (95% CI) = 0.423 (0.230-0.778), -value = 0.005]. However, the associations were insignificant in other inheritance models.

Conclusion: Finally, there were no significant associations between the mentioned SNP and risk of BP2 or MDD in any inheritance model. The present project highlights the role rs594445 in two psychiatric conditions and implies the presence of common genetic factors for these disorders.
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http://dx.doi.org/10.3389/fmolb.2020.540375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542180PMC
September 2020

Hypolipidemic effects of Hypericum Scabrum extract on the serum lipid profile and obesity in high-fat diet fed rats.

Hum Antibodies 2020 Oct 23. Epub 2020 Oct 23.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Diets included high-fat (HFD) and high calories intake is correlated with greater risk of obesity and oxidative stress, which lead to increase the risk of related diseases such as cardiovascular and metabolic disease. In the present study, we have examined the hypolipidemic activity of Hypericum Scabrum extract on HFD fed rats. Fifty-four male Wistar rats divided into six groups: 1) control, 2) H. Scabrum extract (100 mg/kg gavage per day), 3) H. Scabrum extract (300 mg/kg), 4) HFD, 5) HFD and H. Scabrum extract (100 mg/kg), 6) HFD and H. Scabrum extract (300 mg/kg). The groups were fed their diet and treatment for 3 months. Biochemical analysis showed elevated lipid serum profile in HFD rats compared to control group. H. Scabrum extract supplementation significantly ameliorated triglyceride, total cholesterol and LDL-cholesterol. H. Scabrum extract supplementation leading to increase HDL-cholesterol in HFD treated groups. This experiment showed that H. Scabrum extract decreased HFD complications and might be beneficial herbal drug for treatment of hyperlipidemia and obesity.
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http://dx.doi.org/10.3233/HAB-200430DOI Listing
October 2020

Effects of post-training administration of LY341495, as an mGluR2/3 antagonist on spatial memory deficit in rats fed with high-fat diet.

IBRO Rep 2020 Dec 25;9:241-246. Epub 2020 Sep 25.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

High-fat diets (HFDs) adversely influence glutamate metabolism and neurotransmission. The precise role of the group II metabotropic glutamate receptors (mGluR2/3) antagonist on spatial memory deficit following consumption of HFD has not yet been clarified. Therefore, in this study, we examined the effects of post-training administration of mGluR2/3 antagonism; LY341495 on spatial memory in rats fed with HFD (for 10 weeks) by using Morris Water Maze (MWM) task. The training session for testing memory acquisition in MWM consisted of 4 trials per day for 4 consecutive days. Twenty-four hours after the last training session the spatial probe test (retention) was given. Intraperitoneal injection (i.p) injection of LY341495 was done 30 min before probe test. Our results showed that 10 weeks consumption of HFD had no significant effect on escape latency and swimming distance in memory acquisition. Our finding showed that consumption of a HFD leads to reference memory impairment in the probe test. HFD animals spent less time in the target zone in compare with control animals. Also, LY341495 improved HFD-induced reference memory (retention) impairment. HFD animals treated with LY341495 spent more time in the target zone in compare with HFD animals. Escape latencies to find the visible platform during visual task were same in all experimental groups, indicating no visual impairment in the animals. We propose that a HFD may act through mGluR2/3 within the brain to reduce synaptic plasticity, which impairs memory retrieval, and post-training administration of LY341495 can reduce HFD-induced reference memory impairment.
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http://dx.doi.org/10.1016/j.ibror.2020.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527618PMC
December 2020

Dill tablet and Ocimum basilicum aqueous extract: Promising therapeutic agents for improving cognitive deficit in hypercholesterolemic rats.

J Food Biochem 2020 Dec 4;44(12):e13485. Epub 2020 Oct 4.

Faculty of Medicine, Department of Clinical Biochemistry, Hamadan University of Medical Sciences, Hamadan, Iran.

High-cholesterol diet (HCD) is correlated with Alzheimer's disease (AD) and impairment of memory. This study investigated beneficial therapeutic effects of Dill tablet and Ocimum basilicum (Basil) aqueous extract on hypercholesterolemia-induced cognitive deficits and oxidative stress in hippocampus tissues of rats. Hippocampal Aβ(1-42) level was measured. The gene expression levels of superoxide dismutase and inducible-nitric oxide synthase were determined in hippocampus. Cognitive functions were examined and oxidative status was evaluated in serum and hippocampus. Phytochemical properties and in vitro antioxidant activity of Basil extract were assessed. HCD significantly increased serum cholesterol, induced deposition of Aβ plaque, altered hippocampus morphology, and impaired memory function, whereas receiving Basil extract or Dill tablet increased antioxidant potency in serum and hippocampus and normalized HCD-induced deleterious effects. Basil extract and Dill tablet may exhibit their beneficial effects in AD by lowering serum cholesterol and evoking antioxidant system in the brain. PRACTICAL APPLICATIONS: Dill tablet and Basil aqueous extract lowered serum cholesterol in hypercholesterolemic animal models, therefore, they can be used as hypocholesterolemic agents. These edible herbs significantly retarded deposition of Aβ plaque and normalized hippocampal morphology, thus, they favorably protected hippocampus tissue from deleterious effects-induced by hypercholesterolemia. Dill tablet and Basil aqueous extract also corrected oxide-redox balance and normalized HCD-induced oxidative stress to some extent and significantly improved impairments in learning and memory suggesting that these medicinal plants can be considered as surrogate therapeutic agents for the synthetic medicines in the treatment of AD and in postponement of its complications.
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http://dx.doi.org/10.1111/jfbc.13485DOI Listing
December 2020

Effects of Regular Exercise on Diabetes-Induced Memory Deficits and Biochemical Parameters in Male Rats.

J Mol Neurosci 2020 Oct 1. Epub 2020 Oct 1.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

The main objective of current work was to determine the effects of treadmill-running and swimming exercise on passive avoidance learning (PAL) and blood biochemical parameters in rats with streptozotocin (STZ)-induced diabetes. Male Wistar rats were divided into the following 6 groups (N = 6-8 per group): CON, healthy rats without exercise (N = 8); STZ, diabetic rats without exercise (N = 8); CON-SE, healthy rats subjected to swimming exercise (2 months; N = 6); STZ-SE, diabetic rats subjected to swimming exercise (2 months; N = 7); CON-TE, healthy rats subjected to treadmill exercise (2 months; N = 8); STZ-TE, diabetic rats subjected to treadmill exercise (2 months; N = 8). Diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ. Our results showed that STZ decreased the step-through latency in the retention test (STLr) and increased the time spent in the dark compartment (TDC) when compared with the CON group. However, treadmill-running and swimming exercise in STZ-treated rats increased the STLr and decreased the TDC when compared with STZ-treated rats without exercise in PAL. Blood low-density lipoprotein (LDL) and triglyceride (TG) levels in the STZ group were significantly higher than those in the CON group, whereas plasma total antioxidant capacity (TAC) and levels of catalase (CAT) and glutathione peroxidase (GPx) were lower in the STZ group compared with the CON group. The levels of LDL and TG decreased and the levels of TAC, CAT, and GPx increased in the exercise groups in comparison with the STZ group. The present results indicate that regular exercise enhances learning and memory in diabetic rats and that these effects may occur through activation of the antioxidant system.
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http://dx.doi.org/10.1007/s12031-020-01724-3DOI Listing
October 2020

Clinical and demographic characteristics of patients with COVID-19 infection: Statistics from a single hospital in Iran.

Hum Antibodies 2020 Sep 11. Epub 2020 Sep 11.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.
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http://dx.doi.org/10.3233/HAB-200428DOI Listing
September 2020

Chronic NaHS treatment improves spatial and passive avoidance learning and memory and anxiety-like behavior and decreases oxidative stress in rats fed with a high-fat diet.

Brain Res Bull 2020 11 14;164:380-391. Epub 2020 Sep 14.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.

Cognitive function is impaired by increased consumption of a high-fat diet (HFD). Also, HFD consumption can alter hydrogen sulfide (HS) metabolism. HS is an important signaling molecule with antioxidant effects that regulates multiple functions in the brain. In the present study, we investigated the effect of sodium hydrosulfide (NaHS, an HS donor) on cognitive impairment and oxidative stress changes induced by HFD consumption. Following 11 weeks of HFD regimes in Wistar rats, elevated plus-maze (EPM), Morris water maze (MWM), and passive avoidance learning (PAL) tasks were used to evaluate the anxiety-like behavior and spatial and passive learning and memory, respectively. Daily intraperitoneal injection of NaHS was done during the dietary regimen. Serum and hippocampal oxidative stress biomarkers (malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS)) were measured. We demonstrated that treatment with NaHS ameliorated the impairment in the retrieval of reference memory and passive avoidance learning. Moreover, HFD increased anxiety-like behavior, which was reversed by the administration of NaHS. Additionally, the increase in MDA and TOS and the decrease in TAC induced by HFD in the serum and hippocampus were significantly reduced following administration of NaHS. These results indicate that NaHS could significantly ameliorate HFD-induced spatial and passive learning and memory impairment and anxiety-like behavior, at least in part, via its antioxidant activities. Therefore, the administration of NaHS can provide a therapeutic approach for HFD-induced memory impairment.
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http://dx.doi.org/10.1016/j.brainresbull.2020.09.007DOI Listing
November 2020

Persistent effects of the orexin-1 receptor antagonist SB-334867 on naloxone precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine dependent rats.

Int J Neurosci 2020 Aug 11:1-10. Epub 2020 Aug 11.

Neuroscience Research center, Iran University of Medical Sciences, Tehran, Iran.

Aim Of The Study: In this study, we investigated the effect of long-term administration of orexin receptor 1 (OXR1) antagonist on naloxone-precipitated morphine withdrawal symptoms and nociceptive behaviors in morphine-dependent rats.

Materials And Methods: Wistar rats received subcutaneous (s.c.) injections of morphine (6, 16, 26, 36, 46, 56, and 66 mg/kg, 2 ml/kg) at an interval of 24 h for 7 days. In chronic groups, the OXR1 antagonist, SB-334867 (20 mg/kg, i.p.), or its vehicle, was injected repetitively from postnatal day 1 (PND1)-PND23 and then for the following seven days before each morphine injection. Meanwhile, in acute groups, SB-334867, or its vehicle, was administered before each morphine injection. In groups of rats that were designated for withdrawal experiments, naloxone (2.5 mg/kg, i.p.) was administered after the last injection of morphine. In the formalin-induced pain, the effect of OXR1 inhibition on the antinociceptive effects of morphine was measured by injecting formalin after the final morphine injection.

Results: Animals that received long-term SB-334867 administration before morphine injection demonstrated a significant reduction in chewing, defecation, diarrhea, grooming, teeth chattering, wet-dog shake, and writhing. Inhibiting OXR1 for a long time increased formalin-induced nociceptive behaviors in interphase and phase II of the formalin-induced pain.

Conclusions: Our results indicated that the inhibition of OXR1 significantly reduces the development of morphine dependence and behavioral signs elicited by the administration of naloxone in morphine-dependent rats. Furthermore, the prolonged blockade of OXR1 might be involved in formalin-induced nociceptive behaviors.
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http://dx.doi.org/10.1080/00207454.2020.1802266DOI Listing
August 2020

Influence of the maternal high-intensity-interval-training on the cardiac Sirt6 and lipid profile of the adult male offspring in rats.

PLoS One 2020 3;15(8):e0237148. Epub 2020 Aug 3.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

The susceptibility to cardiovascular disease in offspring could be reduced prior to birth through maternal intervention, before and during pregnancy. We evaluated whether the initiation periods of maternal exercise in preconception and pregnancy periods induce beneficial effects in the adult male offspring. Thirty-two female rats were divided into control and exercise groups. The exercise groups involve exercise before pregnancy or the preconception periods, exercise during pregnancy, and exercise before and during pregnancy. The mothers in the exercise groups were run on the treadmill in different periods. Then the birth weight and weekly weight gain of male offspring were measured, and the blood and left ventricle tissue of samples were collected for analysis of the Sirtuin 6 (Sirt6) and insulin growth factor-2 (IGF-2) gene expression, serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (Cho), and triglycerides (TG). There was no significant difference in the birth weight of offspring groups (P = 0.246) while maternal HIIT only during pregnancy leads to reduce weekly weight gain of offspring. Our data showed that Sirt6 and IGF-2 gene expression was increased (P = 0.017) and decreased (P = 0.047) by maternal exercise prior to and during pregnancy, respectively. Also, the serum level of LDL (p = 0.002) and Cho (P = 0.007) were significantly decreased and maternal exercise leads to improves the running speed of the adult male offspring (p = 0.0176). This study suggests that maternal HIIT prior to and during pregnancy have positive intergenerational consequence in the health and physical readiness of offspring.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237148PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7398538PMC
October 2020

Neurophysiologic implications of neuronal nitric oxide synthase.

Rev Neurosci 2020 08;31(6):617-636

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

The molecular and chemical properties of neuronal nitric oxide synthase (nNOS) have made it a key mediator in many physiological functions and signaling transduction. The NOS monomer is inactive, but the dimer form is active. There are three forms of NOS, which are neuronal (nNOS), inducible (iNOS), and endothelial (eNOS) nitric oxide synthase. nNOS regulates nitric oxide (NO) synthesis which is the mechanism used mostly by neurons to produce NO. nNOS expression and activation is regulated by some important signaling proteins, such as cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), calmodulin (CaM), heat shock protein 90 (HSP90)/HSP70. nNOS-derived NO has been implicated in modulating many physiological functions, such as synaptic plasticity, learning, memory, neurogenesis, etc. In this review, we have summarized recent studies that have characterized structural features, subcellular localization, and factors that regulate nNOS function. Finally, we have discussed the role of nNOS in the developing brain under a wide range of physiological conditions, especially long-term potentiation and depression.
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http://dx.doi.org/10.1515/revneuro-2019-0111DOI Listing
August 2020

Phospholipase Cβ3 in the hippocampus may mediate impairment of memory by long-term blockade of orexin 1 receptors assessed by the Morris water maze.

Life Sci 2020 Sep 3;257:118046. Epub 2020 Jul 3.

Department of Laboratory Sciences, Allied Medical College, Iran University of Medical Sciences, Tehran, Iran.

Orexin-A is an endogenous peptide with receptors throughout the brain. According to some recent research, learning and memory are affected by the central administration of orexin; however, no study so far has investigated the long-term inhibition of the orexinergic system. The present study has evaluated the effect of pretraining administration of orexin 1 receptor (OXR1) antagonist, SB-334867, on the acquisition of memory. The Morris water maze (MWM) task was used for training and trial purposes in all groups. Memory performance was analyzed by measuring escape latency, traveled distance, and time spent in the target quadrant. Moreover, the effect of SB-334867 on phospholipase Cβ3 (PLCβ3) levels in the CA1 region of hippocampus slices was examined. Hippocampus slices were prepared using an immunohistochemistry (IHC) approach. SB-334867 (20 mg/kg) increased escape latency in SB-treated rats compared to SB-vehicle group (P < 0.01). SB-treated rats spent less time in the target quadrant compared to the SB-vehicle group (P < 0.001). Distance traveled in the target quadrant was significantly more in SB-treated rats compared to the SB-vehicle group (P < 0.001). Furthermore, SB-334867 decreased PLCβ3 levels in the CA1 of the hippocampus (P < 0.01 and P < 0.05, respectively). Put together, our results suggest that the long-term inhibition of OXR1 plays a prominent role in spatial learning and memory, probably by attenuating PLCβ3 in CA1 neurons.
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http://dx.doi.org/10.1016/j.lfs.2020.118046DOI Listing
September 2020

Increased Levels of IL-34 in Acquired Immune-Mediated Neuropathies.

J Mol Neurosci 2021 Jan 26;71(1):137-141. Epub 2020 Jun 26.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Interleukin (IL)-34 is ligand for the colony-stimulating factor (CSF)-1 receptor. This cytokine has fundamental roles the pathogenesis of a number of autoimmune and neurologic disorders. However, its role in the pathogenesis of acute and chronic inflammatory demyelinating polyneuropathies (AIDP and CIDP) has not been assessed yet. We measured serum levels of IL-34 33 CIDP cases, 16 AIDP cases, and 33 control subjects using commercial ELISA kits. IL-34 levels were significantly higher in both AIDP (44.87 ± 4.38) and CIDP (44.87 ± 4.38) groups compared with healthy subjects (30.10 ± 1.05) (P = 0.046 and P = 0.01, respectively). Differences between female subgroups were insignificant. However, levels of this cytokine were significantly higher in male subjects with CIDP compared with male controls (P = 0.042). Thus, levels of this cytokine might be regarded as biomarkers for these kinds of autoimmune disorders. Future studies are needed to verify these results and find the molecular mechanism of participation of IL-34 in the pathogenesis of AIDP/CIDP.
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http://dx.doi.org/10.1007/s12031-020-01634-4DOI Listing
January 2021

An immunohistochemical study of the effects of orexin receptor blockade on phospholipase C-β3 level in rat hippocampal dentate gyrus neurons.

Biotech Histochem 2020 Jun 25:1-6. Epub 2020 Jun 25.

Neurophysiology Research Center, Hamadan University of Medical Sciences , Hamadan, Iran.

Orexin-A (hypocretin-1) is a neuropeptide that is produced in the lateral hypothalamic area (LHA) and promotes widespread cortical activation. We investigated the effect of SB-334867, a selective orexin receptor 1 (OXR1) antagonist, on phospholipase C-β3 (PLCβ3) level using slices of rat hippocampus preparations and immunohistochemistry. We used three Wistar rats in each of three groups. The control group was untreated rats and SB vehicle and SB groups received SB vehicle and 10 mg/kg SB-334867 daily from postnatal day (PND) 12 to PND30, respectively. We found that the orexin receptor antagonist decreased the PLCβ3 level in the inner and outer blades of dentate gyrus (DG) compared to SB vehicle treated rats. Orexin may increase the PLCβ3 level in most regions of the rat hippocampus.
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http://dx.doi.org/10.1080/10520295.2020.1778088DOI Listing
June 2020

High Levels of Il-19 in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

J Mol Neurosci 2020 Dec 29;70(12):1997-2000. Epub 2020 May 29.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Immune-mediated neuropathies include some specific types such as acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP). Previous studies have demonstrated abnormal cellular or humoral immune responses in these conditions. Although aberrant regulation of several cytokines have been reported in AIDP and CIDP, the significance of interleukin 19 (IL-19) in these conditions have not been elucidated yet. In the current study, we assessed serum levels of IL-19 in 12 CIDP patients (female/male ratio, 4/8), 9 AIDP patients (female/male ratio, 3/6), and 27 normal subjects (female/male ratio. 8/19) using commercial ELISA kits. Notably, we detected higher levels of this cytokine in CIDP patients (136.4 ± 8.57 ng/l) compared with both AIDP patients (93.89 ± 2.26 ng/l) and controls (83.78 ± 1.72 ng/l). However, the differences between AIDP patients and controls were not significant. The current study demonstrates the role of IL-19 in the pathogenesis of CIDP and potentiates this cytokine as a biomarker for this condition.
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http://dx.doi.org/10.1007/s12031-020-01602-yDOI Listing
December 2020

Therapeutic effects of melatonin-treated bone marrow mesenchymal stem cells (BMSC) in a rat model of Alzheimer's disease.

J Chem Neuroanat 2020 10 26;108:101804. Epub 2020 May 26.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; Cellular and molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran. Electronic address:

The therapy based on mesenchymal stem cells(MSCs) has received growing attraction for Alzheimer's disease(AD). However, a great challenge in this regard is the low survival rate of MSCs following transplantation. This study seeks to improve the therapy based on Bone Marrow MSCs (BM-MSCs) through melatonin (MT) pre-treatment, which is 'a known antioxidant' in an animal model of AD. In this paper, we separated BMSCs from the rat tibia and femur bones and then pretreated cells were with 5μM of MT for 24 h.The sample consisted of 40 male Wistar rats randomly assigned to the control, sham,MT-pretreated BMSCs and amyloid-beta (Aβ) peptide BMSCs groups.Two months after the cell transplantation,a number of tests including novel object recognition, Morris water maze, passive avoidance test, and open field test were undertaken. 69 days after the cell therapy,the rats were sacrificed.We removed brain tissues histopathological analysis and carried out immunohistochemistry for Beta tubulin, GFAP and iba1 proteins.The results suggested that both MT-BMSCs and BMSCs moved to brain tissues following the intravenous transplantation.However,MT-BMSCs had a significant effect on boosting learning, cognition and memory in comparison with BMSCs (P < 0.05). Furthermore, there was a significant rise in GFAP and Beta tubulin and substantial fall in microglial cells in the BMSCs in comparison with MT-BMSCs.Stem cell therapy has been proposed as an effective strategy for neurodegenerative diseases,but its therapeutic features are restricted.It has been shown that the pretreatment of MSCs with melatonin partly would boost cells efficiency and thereby alleviate AD complications such as memory and cognition.
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http://dx.doi.org/10.1016/j.jchemneu.2020.101804DOI Listing
October 2020

Assessment of IL-38 Levels in Patients with Acquired Immune-Mediated Polyneuropathies.

J Mol Neurosci 2020 Sep 4;70(9):1385-1388. Epub 2020 May 4.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Acute and chronic inflammatory demyelinating polyneuropathy (AIDP and CIDP) are two types of immune-mediated neuropathies in which abnormal cellular or humoral immune responses have been observed. Although dysregulation of several cytokines has been detected in these disorders, expression of interleukin 38 (IL-38) has not yet been assessed in AIDP and CIDP. In the current study, we evaluated serum concentrations of this member of the IL-1 family of cytokines in 24 patients with CIDP, 13 patients with AIDP and 27 healthy subjects. We detected higher levels of IL-38 in CIDP patients compared with controls. When assessing study subgroups based on gender, there were no significant differences in IL-38 levels among the three female subgroups (P = 0.14). However, the difference among male subgroups was significant (P = 0.010). A Tukey test showed significant differences between male CIDP patients and male controls (P = 0.014). Considering the proposed anti-inflammatory role of IL-38, higher levels of this cytokine in CIDP might reflect the presence of a compensatory mechanism to reduce inflammatory processes in these patients. Further longitudinal assessment of this cytokine is need to test this hypothesis.
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http://dx.doi.org/10.1007/s12031-020-01558-zDOI Listing
September 2020

Comparing the Antinociceptive Effects of Methamphetamine, Buprenorphine, or Both After Chronic Treatment and Withdrawal in Male Rats.

Basic Clin Neurosci 2019 Jul-Aug;10(4):313-322. Epub 2019 Jul 1.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Introduction: Methamphetamine (Meth) and Buprenorphine (BUP) modulate pain perception. However, the antinociceptive effects of their interactions, which affect through different systems, are unclear in rats. This study aimed to compare the analgesic effects of Meth, BUP, and their coadministration, as well as the effect of withdrawal from these substances on nociception in male rats.

Methods: In this experiment, 40 male Wistar rats (weight: 250-300 g) were categorized into four groups: control, Meth, BUP, or BUP+Meth. After seven days of treatments, the antinociceptive effects were assessed using the hot plate and the tail flick tests. The differences among the groups were analyzed with ANOVA and Tukey's post hoc tests. P values less than 0.05 were considered significant.

Results: Meth and BUP increased the reaction times during the hot plate and tail flick tests. The combination of Meth and BUP increased reaction time more than Meth or BUP alone.

Conclusion: The significantly high reaction times in rats treated with Meth and BUP indicate that these substances have antinociceptive effects. In addition, Meth enhanced the antinociceptive effects of BUP. These synergistic effects might occur through the dopaminergic, serotonergic, and or adrenergic systems.
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http://dx.doi.org/10.32598/bcn.9.10.160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101515PMC
July 2019

Assessment of expression profile of microRNAs in multiple sclerosis patients treated with fingolimod.

J Mol Neurosci 2020 Aug 25;70(8):1274-1281. Epub 2020 Mar 25.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Fingolimod is an immunotherapeutic drug approved in certain countries as first-line therapy for relapsing-remitting multiple sclerosis (RRMS). The drug has been shown to alter the expression of several coding and non-coding genes. In the current study, we assessed the expression of miR-506-3p, miR-217, miR-381-3p, miR-1827, miR-449a and miR-655-3p in peripheral blood of patients with RRMS undergoing treatment with fingolimod compared with healthy controls. We also compared the expression of these miRNAs between fingolimod responders and non-responders to determine their relevance with regard to response to fingolimod. Expression of miR-381-3p was significantly higher in responders than in controls (RE difference = 3.903, P = 0.005), while expression of miR-655-3p was significantly lower in both responders and non-responders compared with controls (RE difference = -1.03, P = 0.014; RE difference = -1.41, P < 0.0001, respectively). No difference was found in the expression of other miRNAs between study subgroups. In addition, there was no significant difference in the expression of any miRNA between responders and non-responders. Although there were significant pairwise correlations between expression levels of all of the assessed miRNAs in controls, MS patients exhibited differences in correlation patterns. Expression of miR-381-3p was correlated with age in responders. However, expression of other miRNAs did not correlate with age in any study subgroup. The current study indicates a possible role for miR-655-3p and miR-381-3p in the pathogenesis of MS or possible effects of fingolimod on the expression of these miRNAs. Future studies are needed to verify these results in larger patient populations.
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http://dx.doi.org/10.1007/s12031-020-01537-4DOI Listing
August 2020

Effects of Hypericum scabrum extract on dentate gyrus synaptic plasticity in high fat diet-fed rats.

J Physiol Sci 2020 Mar 24;70(1):19. Epub 2020 Mar 24.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

High-fat diet (HFD) can induce deficits in neural function, oxidative stress, and decrease hippocampal neurogenesis. Hypericum (H.) scabrum extract (Ext) contains compounds that could treat neurological disorders. This study aimed to examine the neuroprotective impacts of the H. scabrum Ext on hippocampal synaptic plasticity in rats that were fed HFD. Fifty-four male Wistar rats (220 ± 10 g) were randomly arranged in six groups: (1) HFD group; (2) HFD + Ext300 group; (3) HFD + Ext100 group; (4) Control group; (5) Ext 300 mg/kg group; (6) Ext 100 mg/kg group. These protocols were administrated for 3 months. After this stage, a stimulating electrode was implanted in the perforant pathway (PP), and a bipolar recording electrode was embedded into the dentate gyrus (DG). Long-term potentiation (LTP) was provoked by high-frequency stimulation (HFS) of the PP. Field excitatory postsynaptic potentials (EPSP) and population spikes (PS) were recorded at 5, 30, and 60 min after HFS. The HFD group exhibited a large and significant decrease in their PS amplitude and EPSP slope as compared to the control and extract groups. In reverse, H. scabrum administration in the HFD + Ext rats reversed the effect of HFD on the PS amplitude and EPSP slope. The results of the study support that H. scabrum Ext can inhibit diminished synaptic plasticity caused by the HFD. These effects are probably due to the extreme antioxidant impacts of the Ext and its capability to scavenge free radicals.
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http://dx.doi.org/10.1186/s12576-020-00747-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093352PMC
March 2020

Treadmill exercise enhances the promoting effects of preconditioned stem cells on memory and neurogenesis in Aβ-induced neurotoxicity in the rats.

Life Sci 2020 May 2;249:117482. Epub 2020 Mar 2.

Neurophysiology Research Centre, Hamadan University of Medical Sciences, Hamadan, Iran; Department of Anatomy, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address:

Aims: Improving the environment of the injured area and the preconditioning of mesenchymal stem cells (MSCs) are promising approaches to optimize the therapeutic properties of transplanted MSCs. Herein we investigated the synergistic effects of treadmill exercise and dimethyloxalylglycine (DMOG)-preconditioned stem cells in an Alzheimer's disease (AD) animal model.

Materials And Methods: The MSCs were treated with DMOG for 24 h and transplanted in the AD model intravenously. In addition to cell transplantation, the rats went on treadmill exercise for one month. Memory function, BDNF expression, neurogenesis, apoptosis, and antioxidant capacity were assessed using shuttle box and Morris water maze tasks, ELISA, immunohistochemistry, western blot, and biochemical methods.

Key Findings: Transplantation of DMOG-treated cells caused a memory improvement compared to the AD group via an increase in neurogenesis and expression of nestin, Sox-2, and NeuroD. Moreover, the injection of preconditioned cells was more effective in increasing the total antioxidant capacity and the BDNF level and decreasing the MDA and caspase-3 than the non-treated cells. Treadmill exercise improved spatial memory and learning through an increase in BDNF and neurogenesis. Finally, treadmill exercise and transplantation of the treated cells together had the most neuroprotective effects.

Significance: It seems that the transplantation of DMOG-treated cells besides exercise may have protective effects in the AD model via an increase in BDNF, antioxidants, and neurogenesis and a decrease in apoptosis.
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http://dx.doi.org/10.1016/j.lfs.2020.117482DOI Listing
May 2020

Association between polymorphisms and risk of ischemic stroke.

Int J Neurosci 2021 Jan 26;131(1):44-48. Epub 2020 Feb 26.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

The methylene tetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme which catalyzes the conversion of homocysteine to methionine. Two single nucleotide polymorphisms (SNPs) within this gene namely rs1801133 (C677T) and rs1801131 (A1298C) have been associated with elevated risk of ischemic stroke and total serum homocysteine in some populations. To assess associations between MTHFR SNPs and risk of ischemic stroke in Iranian population. In the current case-control study, we genotyped rs1801133 and rs1801131 SNPs in 318 Iranian patients with history of ischemic stroke and 400 age- and sex-matched controls using tetra-primer amplification refractory mutation system-polymerase chain reaction method. The rs1801133 was significantly associated with risk of stroke in recessive model (OR (95% CI) = 1.89 (1.12-3.20),  = 0.03). The CT haplotype (rs1801131 and rs1801133, respectively) was significantly over-represented in patients compared with controls (OR (95% CI) = 1.71 (0.25-2.32),  = 0.002). Consequently, our data demonstrate contribution of variants in risk of ischemic stroke in Iranian population.
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http://dx.doi.org/10.1080/00207454.2020.1733554DOI Listing
January 2021

polymorphisms are not associated with ischemic stroke in Iranian population.

Nucleosides Nucleotides Nucleic Acids 2020 3;39(5):792-798. Epub 2020 Feb 3.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

: Ischemic stroke is the main neurological cause of acquired incapability in adults and a prominent cause of mortality. Several association studies have been conducted to explore the role of candidate genes in this neurological condition.: In the present study, we aimed at identification of association between () and risk of ischemic stroke in Iranian population. Two intronic variants within this gene (rs6782011 and rs779867) were genotyped in 318 sporadic ischemic stroke cases and 300 unrelated, healthy controls individuals.: No significant difference was found in allele, genotype or haplotype frequencies of these SNPs between cases and controls after correction for multiple comparisons.: Consequently, the assessed variants are not implicated in risk of ischemic stroke in Iranian population.
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http://dx.doi.org/10.1080/15257770.2019.1697883DOI Listing
December 2020

The protective and therapeutic effects of vinpocetine, a PDE1 inhibitor, on oxidative stress and learning and memory impairment induced by an intracerebroventricular (ICV) injection of amyloid beta (aβ) peptide.

Behav Brain Res 2020 04 25;383:112512. Epub 2020 Jan 25.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Alzheimer's disease (AD) is a neurodegenerative disease leading to cognitive and memory impairment. This study aimed at investigating the therapeutic and preserving effects of vinpocetine on amyloid beta (Aβ)-induced rat model of AD. Sixty male adult Wistar rats were randomly divided into 6 groups (n = 10 per group) as follows: 1; control, 2; sham, 3; Aβ, 4; pre-treatment (vinpocetine + Aβ): oral gavage administration of vinpocetine at 4 mg/kg for 30 days followed by intracerebroventricular (ICV) injection of Aβ, 5; treatment (Aβ + vinpocetine): Aβ ICV injection followed by vinpocetine administration for 30 days, 6; pre-treatment + treatment (vinpocetine + Aβ + vinpocetine): vinpocetine administration for 30 days before and 30 days after AD induction. Following treatments, the animals' learning and memory were investigated using passive avoidance learning (PAL) task, Morris water maze (MWM), and novel object recognition (NOR) tests. The results demonstrated that Aβ significantly enhanced escape latency and the distance traveled in the MWM, decreased step-through latency, and increased time spent in the dark compartment in PAL. Vinpocetine ameliorated the Aβ-infused memory deficits in both MWM and PAL tests. Administration of vinpocetine in the Aβ rats increased the discrimination index of the NOR test. It also significantly diminished the nitric oxide and malondialdehyde levels and restored the reduced glutathione (GSH) levels. Vinpocetine can improve memory and learning impairment following Aβ infusion due to its different properties, including antioxidant effects, which indicates that vinpocetine administration can lead to the amelioration of cognitive dysfunction in AD.
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http://dx.doi.org/10.1016/j.bbr.2020.112512DOI Listing
April 2020

Effects of intra-dentate gyrus microinjection of myokine irisin on long-term potentiation in male rats.

Arq Neuropsiquiatr 2019 12;77(12):881-887

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.

Objective: Induction of long-term potentiation (LTP) increases the storage capacity of synapses in the hippocampal dentate gyrus (DG). Irisin is a myokine generated from FNDC5 (a gene precursor) during exercise.

Methods: Although intra-cornu ammonis 1 administration of irisin fortifies LTP in mice with Alzheimer's disease, the effects of intra-DG injection of irisin on the LTP in rats remains to be elucidated in vivo. In this study, male Wistar rats were randomly divided into a control group (saline), irisin (0.5, 1, and 1.5 μg/rat), and dimethyl sulfoxide (DMSO).

Results: After treatment, the population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in the DG of rats in vivo. Moreover, following completion of the experiments, the stimulating and recording sites in the hippocampus were confirmed histologically from brain sections. Furthermore, biochemical assays like malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were evaluated (the antioxidant markers were analyzed in the plasma).

Conclusion: Our results suggest that all doses of irisin (0.5, 1, 1.5 μg/rat) caused an increase in the EPSP slope and PS amplitude when compared with the control group. In addition, the results obtained showed that irisin decreased TOS and MDA levels while increasing TAC levels as a marker of lipid peroxidation in plasma. The present report provides direct evidence that irisin affects the activity-dependent synaptic plasticity in the dentate gyrus.
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http://dx.doi.org/10.1590/0004-282X20190184DOI Listing
December 2019

Sexual dimorphism in up-regulation of suppressors of cytokine signaling genes in patients with bipolar disorder.

BMC Psychiatry 2019 12 16;19(1):402. Epub 2019 Dec 16.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Proteins encoded by Suppressors of cytokine signaling (SOCS) genes have critical roles in the regulation of immune responses. Meanwhile, several lines of evidence support the presence of immune dysfunction in bipolar disorder (BD) patients.

Methods: In the present study, we assessed expression levels of SOCS1-3 and SOCS5 genes in peripheral blood of patients with BD and healthy subjects.

Results: All SOCS genes were up-regulated in patients compared with healthy subjects. However, when comparing patients with sex-matched controls, the significant differences were observed only in the male subjects except for SOCS5 which was up-regulated in both male and female patients compared with the corresponding control subjects. Significant pairwise correlations were found between expression levels of genes in both patients and controls. Based on the area under curve values, SOCS5 had the best performance in the differentiation of disease status in study participants (AUC = 0.92). Combination of four genes increased the specificity of tests and resulted in diagnostic power of 0.93.

Conclusion: Taken together, these data suggest a role for SOCS genes in the pathogenesis of BD especially in the male subjects. Moreover, peripheral expression levels of SOCS genes might be used as a subsection of a panel of diagnostic biomarkers in BD.
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http://dx.doi.org/10.1186/s12888-019-2396-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915962PMC
December 2019

Expression Analysis of BDNF, BACE1, and Their Natural Occurring Antisenses in Autistic Patients.

J Mol Neurosci 2020 Feb 23;70(2):194-200. Epub 2019 Nov 23.

Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Autism spectrum disorder (ASD) as a multifaceted neurological syndrome affects many aspects of neuropsychologic functions. Dysregulated expressions of several genes have been documented in ASD patients. The current project aimed at comparison of transcript levels of brain derived neurotrophic factor (BDNF), beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), and their natural occurring antisenses in the peripheral blood of ASD individuals (n = 50, male/female = 38/12, age (mean ± standard deviation (SD)): 6 ± 1.4, age range: 3-8) and matched healthy persons (n = 50, male/female = 37/13, age (mean ± SD): 6 ± 1.74, age range: 3-8). We demonstrated remarkable higher levels of these genes in ASD patients. BACE1 transcript levels were correlated with transcript levels of BACE1-AS in all study participants. However, BACE1 transcript levels were not correlated with participants' age. BACE1-AS and BDNF transcript levels were correlated with age in female participants. Significant correlations were detected between transcript levels of BDNF and those of other genes in all study groups. The current results render further indications for contribution of BDNF, BACE1, and their antisenses in the course of ASD and suggested expression levels of these transcripts as putative markers for this neurobehavioral disorder. Such results might be applied in clinical setting for diagnosis of complicated ASD cases.
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http://dx.doi.org/10.1007/s12031-019-01432-7DOI Listing
February 2020

Coenzyme Q10 supplementation reverses diabetes-related impairments in long-term potentiation induction in hippocampal dentate gyrus granular cells: An in vivo study.

Brain Res 2020 01 24;1726:146475. Epub 2019 Sep 24.

Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: https://umsha.ac.ir.

Diabetes mellitus (DM) is associated with impaired hippocampal synaptic plasticity. Coenzyme Q10 (CoQ10) acts as an antioxidant and exerts neuroprotective effects. Accordingly, this study aimed at evaluating the effects of CoQ10 on hippocampal long-term potentiation (LTP) and paired-pulse facilitation (PPF) in streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were randomly divided into six groups (n = 8 per group) as follows and treated for 90 days: the control, control + low dose of CoQ10 (100 mg/kg), control + high dose of CoQ10 (600 mg/kg), diabetic, diabetic + low dose of CoQ10, and diabetic + high dose of CoQ10 groups. Diabetes was induced by a single intraperitoneal injection of 50 mg/kg STZ. The population spike (PS) amplitude and slope of excitatory post synaptic potentials (EPSPs) were measured in dentate gyrus (DG) area in response to the stimulation applied to the perforant path (PP). The results showed that the STZ-induced diabetes impaired LTP induction in the PP-DG synapses. This finding is supported by the decreased EPSP slope and PS amplitude of LTP (P < 0.05). Both low- and high-dose CoQ10 supplementation in the control and diabetic animals enhanced EPSP slope and PS amplitude of LTP in the granular cells of DG (P < 0.05). PPF was affected by LTP induction in diabetic animals receiving the high dose of CoQ10 (P < 0.05). It is suggested that CoQ10 administration could attenuate deteriorative effect of STZ-induced diabetes on in vivo LTP in the DG. The enhanced transmitter release can be partly one of the possible underlying mechanism(s) responsible for the LTP induction in the diabetic animals treated with CoQ10.
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http://dx.doi.org/10.1016/j.brainres.2019.146475DOI Listing
January 2020

Nicotinamide nucleotide transhydrogenase expression analysis in multiple sclerosis patients.

Int J Neurosci 2019 Dec 2;129(12):1256-1260. Epub 2019 Sep 2.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences , Tehran , Iran.

: Nicotinamide nucleotide transhydrogenase (NNT) is a mitochondrial redox-induced proton pump that links NADPH synthesis to the mitochondrial metabolic pathway. It also participates in the regulation of immune responses. A long non-coding RNA namely () has been shown to be transcribed from the same locus and exert anti-proliferative effects in some tissues. : In the current study, we evaluated expression of and in peripheral blood of 50 relapsing-remitting multiple sclerosis patients compared with healthy subjects. The difference in expression was significant in only in male subjects aged over 50 when compared with the corresponding control subgroup. : For , based on the results of Quantile regression and adjustment of the effects of age and sex as well as the interaction between sex and disease status, no significant difference was found between cases and controls. Moreover, and expressions were correlated with age in controls and in female subjects respectively. : Finally, we assessed correlations between expressions of these genes and detected significant pairwise correlations between transcript levels of and genes in both cases and controls. The current study highlights a gender-specific role for in the pathogenesis of MS.
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http://dx.doi.org/10.1080/00207454.2019.1660655DOI Listing
December 2019