Nitric Oxide is Protective Against Mercury Induced Depression

A B S T R A C T Introduction: Mercury is the second most metal pollutant in the world and has the potential to induce many pathologic conditions, especially in nervous system, such as depression. Here we tried to find out if nitric oxide has any possible role in the pathophysiology of depression induced by this metal. Although the role of nitric oxide has been shown in mood control, here we use specific doses of nitric oxide inducer and/or inhibitors which had no effect on normal rats. Methods: 120 male wistar rats weighting 200-250 gram were divided into two main groups: control and methyl mercury(MM) treated. Each main group was divided into four different sub-goups: Saline, L-Arginine, L-Name or 7-nitroindazole (7-NI) respectively. The duration of taking MM or saline was daily for 15 days for both. After the 15th injection a forced swimming test was done. This test shows behavioral immobility (BI) or latency of attempt to escape (LAE), as a depression indicator. Results: Our study showed that low dose L-arginine is protective against MM induced depression as it could turn behavioral immobility (BI) to normal levels in groups taking MM plus L-Arginine, while in group taking just MM, BI was much longer showing the intensity of depression. L-Name and 7-NI did aggravated depression in MM groups but not control ones, on the other hand just in the case of 7-NI the result was significant. Discussion: Our results showed 1) MM could induce depression in rat 2) L-Arginine could improve depression to normal situation in MM group, while in control group has no effec 3) 7-NI, a selective nNOS inhibitor can aggravate mental depression in intoxicated rats. These results showed the important role of nNOS in protection against MM induced depression

Effects of dalteparin on structure of hippocampal neurons of rats in chronic stress

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

Dalteparin as a Novel Therapeutic Agent to Prevent Diabetic Encephalopathy by Targeting Oxidative Stress and Inflammation

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

Pimecrolimus 1 percent cream and pulsed dye laser in treatment of a patient with reticular erythematous mucinosis syndrome

We report on the efficacy of twice daily application of pimecrolimus 1 percent cream in a 48-year-old woman with reticular erythematous mucinosis (REM) syndrome and compare its results with pulsed dye laser (PDL) on the other side of her chest and back. The patient was previously treated by hydroxychloroquine but only a fair response was observed. After application of 5 months of pimecrolimus, the lesions completely resolved and the result was comparable with the other side of her body treated by pulsed dye laser PDL. Topical pimecrolimus and pulsed dye laser appear to be effective and safe treatments for REM. © 2007 Dermatology Online Journal

Diabetic Encephalopathy Affecting Mitochondria and Axonal Transport Proteins

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

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

Introduction: Mood disorders such as anxiety and depression are common following menopause and andropause. The 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 not clear yet. 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 decreases LH release) (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 1- 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 the new object recognition memory in both female (P = 0.472) and male rats (P = 0.798). Conclusion: On the whole, 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 behavior in gonadectomized female rats. The effect of increased LH on cognitive functions such as new object recognition memory was not evident in this study needs further studies and should be interpreted with caution