Mesenchymal stem cell-derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach.

BACKGROUND: Methamphetamine (METH) is a psychostimulant substance with highly addictive and neurotoxic effects, but no ideal treatment option exists to improve METH-induced neurocognitive deficits. Recently, mesenchymal stem cells (MSCs)-derived exosomes have raised many hopes for treating neurodegenerative sequela of brain disorders. This study aimed to determine the therapeutic potential of MSCs-derived exosomes on cognitive function and neurogenesis of METH-addicted rodents. METHODS: Male BALB/c mice were subjected to chronic METH addiction, followed by intravenous administration of bone marrow MSCs-derived exosomes. Then, the spatial memory and recognition memory of animals were assessed by the Barnes maze and the novel object recognition test (NORT). The neurogenesis-related factors, including NeuN and DCX, and the expression of Iba-1, a microglial activation marker, were assessed in the hippocampus by immunofluorescence staining. Also, the expression of inflammatory cytokines, including TNF-α and NF-κB, were evaluated by western blotting. RESULTS: The results showed that BMSCs-exosomes improved the time spent in the target quadrant and correct-to-wrong relative time in the Barnes maze. Also, NORT's discrimination index (DI) and recognition index (RI) were improved following exosome therapy. Additionally, exosome therapy significantly increased the expression of NeuN and DCX in the hippocampus while decreasing the expression of inflammatory cytokines, including TNF-α and NF-κB. Besides, BMSC-exosomes down-regulated the expression of Iba-1. CONCLUSION: Our findings indicate that BMSC-exosomes mitigated METH-caused cognitive dysfunction by improving neurogenesis and inhibiting neuroinflammation in the hippocampus.

Exosomes as a therapeutic tool to promote neurorestoration and cognitive function in neurological conditions: Achieve two ends with a single effort.

Exosomes possess a significant role in intercellular communications. In the nervous system, various neural cells release exosomes that not only own a role in intercellular communications but also eliminate the waste of cells, maintain the myelin sheath, facilitate neurogenesis, and specifically assist in normal cognitive function. In neurological conditions including Parkinson's disease (PD), Alzheimer's disease (AD), traumatic brain injury (TBI), and stroke, exosomal cargo like miRNAs take part in the sequela of conditions and serve as a diagnostic tool of neurological disorders, too. Exosomes are not only a diagnostic tool but also their inhibition or administration from various sources like mesenchymal stem cells and serum, which have shown a worthy potential to treat multiple neurological disorders. In addition to neurodegenerative manifestations, cognitive deficiencies are an integral part of neurological diseases, and applying exosomes in improving both aspects of these diseases has been promising. This review discusses the status of exosome therapy in improving neurorestorative and cognitive function following neurological disease.

AMPK Signaling Pathway as a Potential Therapeutic Target for Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease caused by the loss of dopaminergic neurons. Genetic factors, inflammatory responses, oxidative stress, metabolic disorders, cytotoxic factors, and mitochondrial dysfunction are all involved in neuronal death in neurodegenerative diseases. The risk of PD can be higher in aging individuals due to decreased mitochondrial function, energy metabolism, and AMP-activated protein kinase (AMPK) function. The potential of AMPK to regulate neurodegenerative disorders lies in its ability to enhance antioxidant capacity, reduce oxidative stress, improve mitochondrial function, decrease mitophagy and macroautophagy, and inhibit inflammation. In addition, it has been shown that modulating the catalytic activity of AMPK can protect the nervous system. This article reviews the mechanisms by which AMPK activation can modulate PD.

Chronic stress-induced anxiety-like behavior, hippocampal oxidative, and endoplasmic reticulum stress are reversed by young plasma transfusion in aged adult rats.

Objectives: Aging and stress synergistically induce behavioral dysfunctions associated with oxidative and endoplasmic reticulum (ER) stress in brain regions. Considering the rejuvenating effects of young plasma on aging brain function, in the current study, we examined the effects of young plasma administration on anxiety-like behavior, NADH oxidase, NADPH oxidase, and ER stress markers in the hippocampus of old male rats. Materials and Methods: Young (3 months old) and aged (22 months old) rats were randomly assigned into five groups: young control (Y), aged control (A), aged rats subjected to chronic stress for four weeks (A+S), aged rats subjected to chronic stress and treated with old plasma (A+S+OP), and aged rats subjected to chronic stress and treated with young plasma (A+S+YP). Systemic injection of (1 ml) young and old plasma was performed for four weeks (3 times/week). Results: Young plasma transfusion significantly improved anxiety-like behavior in aged rats and modulated oxidative stress in the hippocampus, evidenced by the increased NADH oxidase (NOX) activity and the reduced NADPH oxidase. In addition, the levels of C/EBP homologous protein (CHOP) and Glucose-Regulated Protein 78 (GRP-78), as ER stress markers, markedly reduced in the hippocampus following the administration of young plasma. Conclusion: These findings suggest that young plasma transfusion could reverse anxiety-like behavior in stress-exposed aged rats by modulating the hippocampal oxidative and ER stress markers.

Aging impairs recovery from stress-induced depression in male rats possibly by alteration of microRNA-101 expression and Rac1/RhoA pathway in the prefrontal cortex.

Along with altering brain responses to stress, aging may also impair recovery from depression symptoms. In the present study, we investigated depressive-like behaviors in young and aged rats and assayed the levels of microRNA-101 (miR-101), Rac1/RhoA, PSD-95, and GluR1 in the prefrontal cortex (PFC) after stress cessation and after a recovery period. Young (3 months old) and aged (22 months old) male Wistar rats were divided into six groups; Young control (YNG), young rats received chronic stress for four weeks (YNG + CS), young rats received chronic stress for four weeks followed by a 6-week recovery period (YNG + CS + REC), Aged control (AGED), aged rats received chronic stress for four weeks (AGED + CS), and aged rats received chronic stress for four weeks followed by a 6-week recovery period (AGED + CS + REC). Stress-induced depression, evaluated by the sucrose preference test (SPT) and forced swimming test (FST), was yet observed after the recovery period in aged but not in young rats, which were accompanied by unchanged levels of miR-101, Rac1/RhoA, GluR1, and PSD-95 in the PFC of aged rats. These data suggested that impaired synaptic plasticity of glutamatergic synapses via the miR-101/Rac1/RhoA pathway may contribute to the delayed behavioral recovery after stress exposure observed in aging animals.

Chronic stress-induced apoptosis is mitigated by young mitochondria transplantation in the prefrontal cortex of aged rats.

Objectives: Apoptosis is common and often comorbid with aging and stress-related mood disorders. Evidence suggests that fresh mitochondria could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young mitochondria administration on the apoptosis process in the prefrontal cortex (PFC) of aged rats exposed to chronic stress. Materials and Methods: Aged (22 months old) male rats were randomly assigned into four groups: aged control (AC), aged rats treated with young mitochondria (A+M), aged rats subjected to chronic stress for four weeks (A+St), and aged rats subjected to chronic stress and treated with young mitochondria (A+St+M). A+M and A+St+M groups received a single ICV injection (10 µl) of fresh mitochondria isolated from the brain of young rats for five minutes (2 µl/min). Finally, the levels of Malondialdehyde (MDA), Cytochrome c (Cyt c), Bax, Bcl-2, and Caspase-3 expression were investigated in the PFC. Results: Young mitochondria administration reduced neuronal apoptosis in the PFC, associated with down-regulation of MDA, Bax, and Caspase-3 and up-regulation of Bcl-2. Moreover, fresh mitochondria partially improved the chronic stress-induced mitochondrial dysfunction in aged rats, as indicated by reduced cytochrome c (Cyt c) release from the mitochondria. Conclusion: These results suggest mitotherapy could reverse cell viability and mitochondrial dysfunction-induced apoptosis in the PFC tissue of aged rats subjected to stressful stimuli.

Mitotherapy restores hippocampal mitochondrial function and cognitive impairment in aged male rats subjected to chronic mild stress.

This study aimed to determine the effects of mitotherapy on learning and memory and hippocampal kynurenine (Kyn) pathway, mitochondria function, and dendritic arborization and spines density in aged rats subjected to chronic mild stress. Twenty-eight male Wistar rats (22 months old( were randomly divided into Aged, Aged + Mit, Aged + Stress, and Aged + Stress + Mit groups. Aged rats in the stress groups were subjected to different stressors for 28 days. The Aged + Mit and Aged + stress + Mit groups were treated with intracerebroventricular injection (10 µl) of fresh mitochondria harvested from the young rats' brains, and other groups received 10 µl mitochondria storage buffer. Spatial and episodic-like memories were assessed via the Barnes maze and novel object recognition tests. Indoleamine 2,3-dioxygenase (IDO) expression and activity, Kyn, Tryptophan (TRY), ATP levels, and mitochondrial membrane potential (MMP) were measured in the hippocampus region. Golgi-Cox staining was also performed to assess the dendritic branching pattern and dendritic spines in the hippocampal CA1 subfield. The results showed that mitotherapy markedly improved both spatial and episodic memories in the Aged + Stress + Mit group compared to the Aged + Stress. Moreover, mitotherapy decreased IDO protein expression and activity and Kyn levels, while it increased ATP levels and improved MMP in the hippocampus of the Aged + Stress + Mit group. Besides, mitotherapy restored dendritic atrophy and loss of spine density in the hippocampal neurons of the stress-exposed aged rats. These findings provide evidence for the therapeutic effect of mitotherapy against stress-induced cognitive deterioration in aged rats by improving hippocampal mitochondrial function and modulation of the Kyn pathway.

Hydroxychloroquine attenuated motor impairment and oxidative stress in a rat 6-hydroxydopamine model of Parkinson's disease.

PURPOSE: Parkinson's disease (PD) is associated with the destruction of dopaminergic neurons in the substantia nigra (SN). Hydroxychloroquine (HCQ) has the capability to cross the blood-brain barrier and promote a neuroprotective potential. This study evaluated the effects of HCQ on the 6-hydroxydopamine (6-OHDA)-induced PD model in rats. METHODS: Wistar rats were randomly divided into sham, PD, PD + levodopa and PD + HCQ groups. The PD model was induced by a stereotactic administration of 6-OHDA into the left SN pars compacta (SNpc) and confirmed by rotation and the Murprogo's tests. HCQ (100 mg/kg, p.o.) and levodopa (12 mg/kg, p.o.) were administered once a day for 21 days. Three weeks after surgery, the behavioral tests were performed. Brain lipid peroxidation index (MDA), glutathione peroxidase activity (GPx), total antioxidant capacity (TAC) levels and α-synuclein protein expression in the SN were also measured. RESULTS: The behavioral tests demonstrated that induction of PD increased the muscle rigidity and the number of rotations, which were reversed by HCQ treatment. Also, induction of PD was associated with an increase in α-synuclein protein levels and MDA and decreased TAC levels and GPx activity. However, HCQ decreased α-synuclein and MDA levels while increased TAC levels and GPx activity. In addition, histopathological data showed that HCQ protects dopaminergic neurons against 6-OHDA-induced toxicity. CONCLUSION: According to the results, HCQ has a beneficial effect in improving PD-related pathophysiology, in part, by mitigating oxidative stress and protecting the dopaminergic neurons in the SN.

Targeting Novel microRNAs in Developing Novel Alzheimer's Disease Treatments.

Alzheimer's disease (AD) is considered a multifactorial disease and a significant cause of dementia during aging. This neurodegenerative disease process is classically divided into two different pathologies cerebral accumulation of amyloid-ß and hyperphosphorylated neurofibrillary tau tangles. In recent years, massive efforts have been made to treat AD by decreasing amyloid-ß and tau in the brains of patients with AD, with no success. The dysfunction of a wide range of microRNAs promotes the generation and insufficient clearance of amyloid-ß (Aß) and increases tau plaques which are the pathophysiological markers of AD. Disturbance of these microRNAs is associated with mitochondrial dysfunction, oxidative damage, inflammation, apolipoprotein E4 (APOE4) pathogenic process, synaptic loss, and cognitive deficits induced by AD. Targeting a specific microRNA to restore AD-induced impairments at multiple stages might provide a promising approach for developing new drugs and therapeutic strategies for patients with AD. This review focuses on different mechanisms of microRNAs in AD pathophysiology.

Maternal stress induced anxiety-like behavior exacerbated by electromagnetic fields radiation in female rats offspring.

There is a disagreement on whether extremely low frequency electromagnetic fields (ELF-EMF) have a beneficial or harmful effect on anxiety-like behavior. Prenatal stress induces frequent disturbances in offspring physiology such as anxiety-like behavior extending to adulthood. This study was designed to evaluate the effects of prenatal stress and ELF-EMF exposure before and during pregnancy on anxiety-like behavior and some anxiety-related pathways in the hippocampus of female rat offspring. A total of 24 female rats 40 days of age were distributed into four groups of 6 rats each: control, Stress (rats whose mothers underwent chronic stress), EMF (rats whose mothers were exposed to electromagnetic fields) and EMF/S (rats whose mothers were simultaneously exposed to chronic stress and ELF-EMF). The rats were given elevated plus-maze and open field tests and then their brains were dissected and their hippocampus were subjected to analysis. ELISA was used to measure 24(S)-hydroxy cholesterol, corticosterone, and serotonin levels. Cryptochrome2, steroidogenic acute regulatory protein, 3B-Hydroxy steroid dehydrogenase, N-methyl-D-aspartate receptor 2(NMDAr2) and phosphorylated N-methyl-D-aspartate receptor 2(PNMDAr2) were assayed by immunoblotting. Anxiety-like behavior increased in all treatment groups at the same time EMF increased anxiety induced by maternal stress in the EMF/S group. The stress group showed decreased serotonin and increased corticosterone levels. ELF-EMF elevated the PNMDAr2/NMDAr2 ratio and 24(S)-hydroxy cholesterol compared to the control group but did not change corticosterone. EMF did not restore changes induced by stress in behavioral and molecular tests. The results of the current study, clarified that ELF-EMF can induce anxiety-like behavior which may be attributed to an increase in the PNMDAr2/NMDAr2 ratio and 24(S)-OHC in the hippocampus, and prenatal stress may contribute to anxiety via a decrease in serotonin and an increase in corticosterone in the hippocampus. We also found that anxiety-like behavior induced by maternal stress exposure, is exacerbated by electromagnetic fields radiation.

Mitochondrial transplantation improves anxiety- and depression-like behaviors in aged stress-exposed rats.

Impaired mitochondrial function and abnormalities in the tryptophan (Trp)-kynurenine (Kyn) pathway are linked to age-related mood disorders. This study investigated the effect of intracerebroventricular (ICV) injection of the mitochondria isolated from young rat brain on depression-like behaviors of aged rats subjected to chronic mild stress (CMS). Aged (22 months old) male rats were randomly assigned into four groups: Aged, Aged + Mit, Aged + CMS, and Aged + CMS + Mit. Anxiety- and depression-like behaviors were assessed using elevated plus maze (EPM), open field test (OFT), forced swimming test (FST), and sucrose preference test (SPT). Mitochondrial membrane potential (MMP), ATP levels, indoleamine 2, 3-dioxygenase (IDO) levels, and Kyn metabolites were measured in the prefrontal cortex (PFC). Golgi Cox staining was used to investigate the neuronal morphology. Mitotherapy decreased immobility time and anhedonia in the FST; increased open arm time and entries in the EPM; decreased grooming and increased rearing, center time, and the entrance in the OFT. Mitotherapy also reduced IDO and Kyn metabolites, restored MMP and ATP production, and enhanced dendritic length and spine density in the PFC. Overall, mitotherapy improved anxiety-and depression-like behaviors in aged rats and it could be considered as a new therapeutic strategy for age-related depressive disorders.

Young Plasma Induces Antidepressant-Like Effects in Aged Rats Subjected to Chronic Mild Stress by Suppressing Indoleamine 2,3-Dioxygenase Enzyme and Kynurenine Pathway in the Prefrontal Cortex.

Pathophysiology of depression in elderlies is linked to aging-associated increase in indoleamine 2,3-dioxygenase (IDO) levels and activity and kynurenine (Kyn) metabolites. Moreover, these aging-induced changes may alter the brain's responses to stress. Growing evidence suggested that young plasma can positively affect brain dysfunctions in old age. The present study aimed to investigate whether the antidepressant effects of young plasma administration in aged rats subjected to chronic unpredictable mild stress (CUMS) and underlying mechanisms, focusing on the prefrontal cortex (PFC). Young (3 months old) and aged (22 months old) male rats were divided into five groups; young control, aged control, aged rats subjected to CUMS (A + CUMS), aged rats subjected to CUMS and treated with young plasma (A + CUMS + YP), and aged rats subjected to CUMS and treated with old plasma (A + CUMS + OP). Plasma was injected (1 ml, intravenously) three times per week for four weeks. Young plasma significantly improved CUMS-induced depressive-like behaviors, evidenced by the increased sucrose consumption ratio in the sucrose preference test and the reduced immobility time in the forced swimming test. Furthermore, young plasma markedly reduced the levels of interferon-gamma (IFN-γ), IDO, Kyn, and Kyn to tryptophan (Kyn/Trp) ratio in PFC tissue. Expression levels of the serotonin transporter and growth-associated protein (GAP)-43 were also significantly increased after chronic administration of young plasma. These findings provide evidence for the antidepressant effect of young plasma in old age; however, whether it improves depressive behaviors or faster recovery from stress-induced deficits is required to be elucidated.

Hepatoprotection of capsaicin in alcoholic and non-alcoholic fatty liver diseases.

Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are common causes of chronic liver disease that share the range of steatosis, steatohepatitis, fibrosis, cirrhosis, and finally, hepatocellular carcinoma. They are identified by the dysregulation of disease-specific signalling pathways and unique microRNAs. Capsaicin is an active ingredient of chilli pepper that acts as an agonist of transient receptor potential vanilloid subfamily 1. It seems that the protective role of capsaicin against NAFLD and ALD is linked to its anti-steatotic, antioxidant, anti-inflammatory, and anti-fibrotic effects. Capsaicin-induced inhibiting metabolic syndrome and gut dysbiosis and increasing bile acids production are also involved in its anti-NAFLD role. This review summarises the different molecular mechanisms underlying the protective role of capsaicin against NAFLD and ALD. More experimental studies are needed to clarify the effects of capsaicin on the expression of genes involved in hepatic lipid metabolism and hepatocytes apoptosis in NAFLD and ALD.

The role of miRNAs in the regulation of autophagy in autoimmune diseases.

Autoimmune diseases (AD), which are classified as chronic injuries, are caused by a specific auto-reactive reaction. The etiology of most ADs is not well understood. Meanwhile, Autophagy is a protective response defining as a catabolic method by lysosomes tending to maintain homeostasis acts by recycling and discrediting cell compartments. Autophagy plays a crucial role in controlling immune homeostasis by eliminating intracellular pathogens and presenting antigens to immune cognition. MicroRNAs are commonly known as endogenous non-coding small RNAs, which span 18-25 nt and take part in the gene expression at the post-transcriptional level regulation. miRNAs play important roles in different processes like, cell differentiation, duplicating, and apoptosis. Moreover, miRNAs are the critical molecules for the regular function of the immune system by modulating immune tolerance mechanisms and autoimmunity. Recent findings support the role of dysregulated miRNAs in the pathogenesis of ADs and in the regulation of autophagy. In this review, we will focus on the role of the miRNAs in the regulation of autophagy and then will explain the role of dysregulated miRNAs in the initiation of the ADs by modulating autophagy.

Young plasma administration mitigates depression-like behaviours in chronic mild stress-exposed aged rats by attenuating apoptosis in prefrontal cortex.

NEW FINDINGS: What is the central question of this study? Young plasma contains several rejuvenating factors that exert beneficial effects in ageing and neurodegenerative diseases: can repeated transfusion of young plasma improve depressive behaviour in aged rats? What is the main finding and its importance? Following chronic transfusion of young plasma, depressive behaviour was improved in the depression model of aged rats, which was associated with reduced apoptosis process in the prefrontal cortex. ABSTRACT: Brain ageing alters brain responses to stress, playing an essential role in the pathophysiology of late-life depression. Moreover, apoptotic activity is up-regulated in the prefrontal cortex in ageing and stress-related mood disorders. Considerable evidence suggests that factors in young blood could reverse age-related dysfunctions in organs, especially in the brain. Therefore, this study investigated the effect of young plasma administration on depressive behaviours in aged rats exposed to chronic unpredictable mild stress (CUMS), with a focus on the apoptosis process. Young (3 months old) and aged (22 months old) male rats were randomly assigned into four groups: young control (YC), aged control (AC), aged rats subjected to CUMS (A+CUMS) and aged rats subjected to CUMS and treated with young plasma (A+CUMS+YP). In the A+CUMS and A+CUMS+YP groups, CUMS was used to generate the depression rat model. Moreover, the A+CUMS+YP group received pooled plasma (1 ml, intravenously), collected from young rats, three times per week for 4 weeks. Young plasma administration significantly improved CUMS-induced depression-like behaviours, including decreased sucrose consumption ratio, reduced locomotor activity and prolonged immobility time. Importantly, young plasma reduced neuronal apoptosis in the prefrontal cortex that was associated with reduced TUNEL-positive cells and cleaved caspase-3 protein levels in the A+CUMS+YP compared with the A+CUMS group. Young plasma can partially improve the neuropathology of late-life depression through the apoptotic signalling pathways.

Sodium nitrate preconditioning prevents progression of the neuropathic pain in streptozotocin-induced diabetes Wistar rats.

PURPOSE: The purpose of the study was to evaluate the possible protective effects of low dose sodium nitrate preconditioning on the peripheral neuropathy in streptozotocin (STZ)-induced diabetic model. METHODS: Male Wistar rats were randomly divided into five groups: control (no intervention), control treated sodium nitrate (100 mg/L in drinking water), diabetic (no intervention), diabetic treated NPH insulin (2-4 U), and diabetic treated sodium nitrate (100 mg/L in drinking water). Diabetes was induced by intraperitoneal injection of STZ (60 mg/kg). All interventions were done for 60 days immediately following diabetes confirmation. Thermal and mechanical algesia thresholds were measured by means of hot-plate test, von Frey test, and tail-withdrawal test before the diabetic induction and after diabetes confirmation. At the end of the experiment, serum NOx level and serum insulin level were assessed. Blood glucose concentration and body weight have recorded at the base and duration of the experiment. RESULTS: Both hypoalgesia, hyperalgesia along with allodynia developed in diabetic rats. Significant alterations including, decrease in tail withdrawal latency (30th day), decreased mechanical threshold (60th day), and an increase in hot plate latency (61st day) were displayed in diabetic rats compared to control rats. Nitrate and insulin preconditioning produced protective effects against diabetes-induced peripheral neuropathy. Data analysis also showed a significant increase in glucose level as well as a considerable reduction in serum insulin and body weight of diabetic rats, which restored by both insulin and nitrate preconditioning. CONCLUSION: Sodium nitrate preconditioning produces a protective effect in diabetic neuropathy, which may be mediated by its antihyperglycemic effects and increased serum insulin level.

Effects of transcranial photobiomodulation and methylene blue on biochemical and behavioral profiles in mice stress model.

The effectiveness of transcranial photobiomodulation (tPBM) and methylene Blue (MB) in treating learning and memory impairments is previously reported. In this study, we investigated the effect of tPBM and MB in combination or alone on unpredictable chronic mild stress (UCMS)-induced learning and memory impairments in mice. Fifty-five male BALB/c mice were randomly allocated to five groups: control, laser sham + normal saline (NS), tPBM + NS, laser sham + MB, and tPBM + MB. All groups except the control underwent UCMS and were treated simultaneously for 4 weeks. Elevated plus maze (EPM) was used to evaluate anxiety-like behaviors. Novel object recognition (NOR) test and Barnes maze tests were used to evaluate learning and memory function. The serum cortisol and brain nitric oxide (NO), reactive oxygen species (ROS), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels were measured by spectrophotometric methods. Behavioral tests revealed that UCMS impaired learning and memory, and treatment with PBM, MB, and their combination reversed these impairments. Levels of NO, ROS, SOD activity in brain, and serum cortisol levels significantly increased while brain GPx activity and total antioxidant capacity significantly decreased in the sham + NS animals when compared with the controls. A significant improvement was observed in treatment groups due to reversion of the aforementioned molecular analysis caused by UCMS when it was compared with control levels. Both tPBM and MB in combination or alone have significant therapeutic effects on learning and memory impairments in UCMS-received animals.

Garlic (Allium sativum) improves anxiety- and depressive-related behaviors and brain oxidative stress in diabetic rats.

This study investigated the effects of garlic on anxiety- and depression-related behaviors and brain oxidative markers in streptozotocin (STZ)-induced diabetes in rats. Fifty-six male Wistar rats were randomly divided into seven experimental groups (n = 8/group): control, diabetic + saline, diabetic + garlic, diabetic + imipramine, and diabetic + diazepam groups. Animals received garlic homogenate (0.1, 0.25, and 0.5 g/kg) for 10 days. At the end of the treatments, anxiety- and depressive-related behaviors were evaluated by elevated plus maze (EPM) and forced swimming test (FST), respectively. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and malondialdehyde (MDA) levels were measured in the brain. Diabetic + garlic (0.5 g/kg) group showed lower anxiety- and- depressive-like behaviors as compared to the diabetic rats. Furthermore, garlic treatment (0.5 g/kg) attenuated MDA levels and enhanced SOD and GPx activities in the brain. Our findings indicate that garlic alleviates anxiety- and depression-related behaviors in the diabetic rats possibly by attenuation of brain oxidative stress.

Physical and cognitive training attenuate hippocampal ischemia-induced memory impairments in rat.

The present study aimed to evaluate the preventive role of physical and cognitive training separately or in combination on memory dysfunction, inflammatory factors and apoptotic markers in the hippocampal-ischemia model of rat. The ischemia model was established by infusion of endothelin-1 (ET-1) into the animal's hippocampus using stereotaxic surgery. Physical, cognitive and combination training groups exposed to voluntary running wheel exercise or modified Barnes maze cognitive task or combination of this interventions for 4 weeks, respectively. Next, Morris water maze (MWM) and novel object recognition (NOR) tasks were used to assess recognition and spatial learning and memories. Western blotting was used to evaluate the protein levels of Nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor-alpha receptor 1 (TNFR1), cytochrome c, Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 in the hippocampal tissue. Hippocampal ischemia significantly impaired recognition and spatial learning and memory with an increase of inflammatory and apoptotic proteins in the hippocampus tissue. Interventions in combination or separately significantly improved performance of ischemia-received animals in memory tasks. Furthermore, both physical and cognitive paradigms also reduced inflammatory and apoptotic factors in the hippocampus of ischemia-received rats. These findings indicate that physical and cognitive training separately or in combination attenuates the deleterious effect of ischemia on cognition through its anti-inflammatory and anti-apoptotic properties.

Evaluation of ameliorative effect of sodium nitrate in experimental model of streptozotocin-induced diabetic neuropathy in male rats.

OBJECTIVE: Diabetes induces sensory symptoms of neuropathy as positive (hyperalgesia), negative (hypoalgesia), or both. METHODS: In the present study, fifty male Wistar rats were allocated to five groups: control, control+nitrate, diabetes, diabetes+insulin, and diabetes+nitrate. Thirty days after diabetes confirmation, insulin (2-4 U/day) was injected subcutaneously in diabetes+insulin group and nitrate (100 mg/l) was added into drinking water of the control+nitrate and diabetes+nitrate groups for a period of 2 months. In order to assess the mechanical and thermal algesia, tail immersion, hot plate, and von Frey tests were performed. The serum insulin levels were determined with insulin ELISA Kit. Serum level of NOx was determined by the Griess method. RESULTS: Both thermal and mechanical nociceptive thresholds showed a significant decrease (p<0.05) which was followed by a significant increase (p<0.01) in the thermal nociceptive threshold in the diabetes group. Chronic nitrate or insulin treatment led to a significant decrease (p<0.01) in blood glucose levels, as well as a significant (p<0.05) increase in the body weight and serum NOx. Moreover, nitrate treatment significantly increased serum insulin levels (p<0.001) compared to the other groups. CONCLUSION: Chronic nitrate treatment modified the thermal and mechanical sensitivities in diabetic animals.