Search

Introduction: Mood disorders such as depression and anxiety disorders have been affecting a relatively high proportion of the world's population. Neuroplasticity hypothesis of depression proposes that lack of brain-derived neurotrophic factor (BDNF) can cause structural changes in the brain. The extract of Ginkgo biloba (Gb) leaves can restore much of the damage in the nervous system. We examined the antidepressant role of Gb extract (EGb 761) on BDNF expression modulation in the hippocampus of rats subjected to repeated restraint stress (RRS). Methods: Adult male rats were randomly divided into 10 groups: control, controlvehicle treated, stress, stress-vehicle treated, as well as three control and three experimental groups pretreated with EGb (15, 30, 60mg/kg, IP daily) for 21 days. They underwent restraint stress on a daily basis, 6 hours for 21 consecutive days. Weight changes, locomotor activity and forced swim test (FST) were employed to assess depressive-like symptoms. The serum corticosterone level was also measured by ELISA. Hippocampal BDNF DNA methylation and protein expression were assayed by methylation sensitive restriction enzymes (Real Time PCR) and Western-blotting respectively in all groups. Results: Pre-treatment with 30 and 60 mg/kg/day of Gb extract significantly attenuated depressive-like effects in the body weight, FST and serum corticosterone level in RSS rats compared to control groups. Further, it inhibited chronic stress-induced alterations in the hippocampal BDNF DNA methylation and protein expression. Conclusion: These findings suggest that Gb can induce an antidepressant role through its modulation effect on the hippocampal BDNF expression. [ABSTRACT FROM AUTHOR]

Introduction: Hepcidin is the main modulator of systemic iron metabolism, and its role in the brain has been clarified recently. Studies have shown that hepcidin plays an important role in neuronal iron load and inflammation. This issue is of significance because neuronal iron load and inflammation are pathophysiological processes that are highly linked to neurodegeneration. Moreover, the activity of hepcidin has recently been manipulated to recover the neuronal impairment caused by brain inflammation in animal models. Methods: Streptozotocin (STZ) was used to induce type 1 diabetes. Male Wistar rats (n = 40) with a weight range of 200-250 g were divided into control, diabetic, diabetic + insulin, and diabetic + dalteparin groups. Dalteparin (100 mg/kg IP) and insulin (100 mg/kg SC) were administered for 8 weeks. At the end of the experiment, Y-maze and passive avoidance tasks were carried out. The animals were perfused randomly and their hippocampal tissue was isolated for the analysis of markers such as lipid peroxidation like Malondialdehyde (MDA), hepcidin expression, iron, and ferritin. Blood samples were taken for the measurement of serum inflammatory cytokine Interleukin (IL)-6. Results: The findings indicated that treatment with dalteparin reduced IL-6, MDA, ferritin, and hepcidin expression in diabetic rats compared to treatment with insulin (P<0.05). Moreover, treatment with dalteparin did not decrease the iron level or prevented its decline. Conclusion: Treatment with dalteparin improved the cognitive dysfunctions and symptoms of Alzheimer disease in STZ-induced diabetic rats by appropriately modulating and reducing oxidative stress and neuroinflammation. This may enhance the existing knowledge of therapeutics to reduce cognitive impairment in diabetes and is suggested to be a potential therapeutic agent in diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic encephalopathy is described as any cognitive and memory impairments associated with hippocampal degenerative changes, including the neurodegenerative process and decreased number of living cells. Mitochondrial diabetes (MD) appears following activation of mutant mitochondrial DNA and is a combination of diabetes and cognitive deficit. In this research, we showed the correlation of diabetic encephalopathy, dysfunctional mitochondria, and changes in the expression of axonal transport proteins (KIF5b, Dynein). Methods: Twenty-four male Wistar rats were divided into three groups: (n=8 in each group):1. Control + saline; 2. Diabetic, and 3. Diabetic + insulin. Before starting the experiments, the animals with blood sugar lower than 150 mg/dL entered the study. Diabetes induction was carried out by Intraperitoneal (IP) Streptozotocin (STZ) administration. Fasting Blood Sugar (FBS) and body weight was checked after the first week and at the end of the eighth week. Then, behavioral studies (elevated plus maze, Y-maze, and passive avoidance learning) were performed. After behavioral studies, blood samples were taken to measure serum insulin level and HgbA1c. Next, fresh hippocampal tissue was collected. Gene expression of motor proteins was assessed by real-time PCR and mitochondrial membrane potential by rhodamine123. Results: Our results showed the impairment of HgbA1c, serum insulin, FBS, and weight in the diabetic group (P<0.05). Behavioral tests revealed different degrees of impairment in diabetic rats (P<0.05). KIF5b mRNA expression increased in the hippocampus (P<0.05) with no change in dynein gene expression. These changes were associated with abnormal mitochondrial membrane potential (P<0.05). Conclusion: KIF5b mRNA up-regulation in hippocampal neurons of STZ-diabetic rats is a factor that can be involved in abnormal axonal transport and decreased MMP, leading to impairment of mitochondrial function. These manifestations showed mitochondrial dysfunction in diabetes and resulted in abnormal behavioral tests and diabetic encephalopathy. [ABSTRACT FROM AUTHOR]

Introduction: Stress predisposes organisms to depression and cognitive impairments, and seems to interact with metabolic homeostasis. The inflammatory response and the upregulation of proinflammatory cytokines are some of the consequences related to chronic stress. In this study, we investigated the preventive effect of chronic administration of ibuprofen, as an inhibitor of cyclooxygenases, on the cognitive and behavioral alterations and the weight gain reduction induced by simultaneous chronic restraint stress in rats. Materials and Methods: Male Wistar rats were subjected to chronic restraint stress and injected daily with the variable doses of ibuprofen or vehicle, for 21 consecutive days. Then, all animals were tested with the forced swim test and passive avoidance conditioning. Also, the weight of the animals was recorded before and after the interventions. Ultimately, plasma interleukin 6 (IL-6) levels were measured. Results: Chronic stress increased depressive-like behaviors, impaired learning, and disrupted the normal weight gain. However, the animals that received the highest dose of ibuprofen showed less depressive-like behaviors, a better avoidance memory, and a higher weight gain. However, the level of plasma IL-6 did not differ significantly between the study groups. Conclusion: The administration of ibuprofen prevents the cognitive and behavioral consequences of chronic stress. During the recovery, the plasma levels of IL-6 were not elevated by stress, and the IL-6 levels did not predict the behavioral performance of the stressed animals. The exact mechanisms of the protective effects of ibuprofen against chronic stress need to be further investigated. [ABSTRACT FROM AUTHOR]

Introduction: Mood disorders such as anxiety and depression are common following menopause and andropause. Lack of sex steroid hormones is suggested as the primary cause of these disturbances. The level of luteinizing hormone (LH) would also rise 3-4 times than normal in these people. The potential effects of LH on mood and cognitive symptoms following menopause and andropause are still unknown. This study aimed to investigate the effect of increased LH on novel object discrimination (NOD) memory and anxiety like behavior in gonadectomized rats. Methods: Four-month-old male and female Wistar rats were randomly assigned into 4 groups (in each sex): control rats (Cont), gonadectomized without treatment (GnX), gonadectomized treated with triptorelin, a GnRH agonist which reduces LH release eventually, (GnX+Tr), gonadectomized treated with triptorelin plus sex steroid hormone, estradiol in female and testosterone in male rats (GnX+Tr+S/T). After 4 weeks treatment, anxiety score (elevated plus maze) and NOD were measured. Data were analyzed using One-way ANOVA, and P-values less than 0.05 were considered as significant. Results: Gonadectomy increased anxiety like behaviors (decrease of presence time in the open arms) in female rats (P=0.012), but not in male ones (P=0.662). Additionally, triptorelin alone reduced the increased anxiety score in gonadectomized female rats, compared to group treated with both triptorelin and estradiol. Furthermore, it was shown that gonadectomy and or treatment with triptorelin and sex steroids had no significant effect on novel object recognition memory in both female (P=0.472) and male rats (P=0.798). Conclusion: Findings of this study revealed that increased level of LH following menopause or andropause should be considered as a possible cause for increased anxiety. Also, this study showed that LH reducing agents would reduce anxiety like behavior in gonadectomized female rats. The effect of increased LH on cognitive functions such as novel object recognition memory was not evident in this study and needs further studies. [ABSTRACT FROM AUTHOR]

Depression, as one of the most prevalent and disabling disorders in the world, has a complex and yet not well-known pathophysiology. Genetic, hormonal, neurotransmitter, inflammatory and neurodegenerative theories are all responsible. Studies show that depression leads to structural changes in the hippocampus, prefrontal cortex, amygdala, anterior cingulate, and basal bodies. Hippocampal volume loss is observed due to the death of nerve cells, neurons, and glial cells, and reduced neurogenesis. The hippocampus is a part of the limbic system. The limbic system is the area in the brain that is associated with memory, emotions, and motivation. The limbic system is located just above the brain stem and below the cortex. Despite the many studies related to the reduced hippocampal neurogenesis in depressed patients, no study has compared the amount of neurodegeneration between the left and right hippocampus. In this study, we compared neurodegeneration levels in the right and left hippocampus of the rats. Methods: Twenty male Sprague-Dawley rats that were purchased Razi Institute, Karaj, Iran, were evaluated in the study. This study was conducted in cellular and molecular center in Iran University of Medical Sciences, from June 2012 to June 2013. Half of them had unpredictable chronic mild stress (UCMS) for 21 days to develop depression. The forced-swimming test (FST) was used to measure the immobility time (IB), a symptom of depression. One week after the behavioral test, the rats were prepared for transcardial perfusion. Then, paraffin fixed brain was excised and the hippocampus was prepared for Nissl staining. All above-mentioned procedures were performed for the control group too except inducing UCMS. Results: Our results increased IB in the UCMS group, 68.8 second in stress group and 15.1 second in control group. Nissl staining showed prominent neural degeneration in the hippocampus of the rats in the UCMS group. Comparison of the left and right hippocampal cells revealed that the right hippocampus (mean= 49.166) was more vulnerable to stress than the left hippocampus (mean= 76.6). Conclusion: Our study showed different manifestations of depression after UCMS. It showed that UCMS could lead to mental depression. This study showed that the right hippocampus was more sensitive to stress than the left hippocampus. In fact, UCMS resulted in depression. The study showed that the right hippocampus was more sensitive to stress than the left hippocampus. Therefore, the main function of the right hemisphere, which is adaptation to the new environment, is disturbed more. [ABSTRACT FROM AUTHOR]

Introduction: Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke neurodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats. Methods: the study was carried out on 60 adult male wistar rats, weighing 200- 250 gr. The rats were randomly divided into three groups: control, stress and stress + dalteparin (SD) groups. Animals in the stress and stress + dalteparin group were exposed to chronic stress for 4 weeks. Animals in the stress + dalteparin (SD) group received dalteparin (70,100 and 140 IU/kg/days i.p.) during the stress period. After the last stressor animals were sacrificed and concentration of IL-6 in serum was measured using ELISA. All animals were reperfused and their brains were processed for histological analysis through Nissl analysis. Results: We found that the serum concentration of IL-6 was significantly higher in the CMS (Chronic Mild Stress) exposure group than in the control group (p<0.05). Moreover, dalteparin, dose dependently decreased IL-6 concentration in the SD groups. Chronic stress also resulted in significant cell loss in hippocampal CA1, CA3 and hilus. Dalteparin markedly inhibited the decreases in number of hippocamoal CA1 and CA3 (p<0.01) and hilus (p<0.05) neurons caused by chronic stress. Discussion: chronic stress damages hippocampal CA1, CA3 and hilus neurons, and dalteparin protects hippocampus from damage induced by chronic stress. [ABSTRACT FROM AUTHOR]