Anandamide improves food intake and orexinergic neuronal activity in the chronic sleep deprivation induction model in rats by modulating the expression of the CB1 receptor in the lateral hypothalamus.

Sleep deprivation alters orexinergic neuronal activity in the lateral hypothalamus (LH), which is the main regulator of sleep-wake, arousal, appetite, and energy regulation processes. Cannabinoid receptor (CBR) expression in this area is involved in modulating the function of orexin neurons. In this study, we investigated the effects of endocannabinoid anandamide (AEA) administration on improving food intake and appetite by modulating the activity of orexin neurons and CB1R expression after chronic sleep deprivation. Adult male Wistar rats (200-250 g) were randomly divided into three groups: control + vehicle (Control), chronic sleep deprivation + vehicle (SD), and chronic sleep deprivation +20 mg/kg AEA (SD + A). For SD induction, the rats were kept in a sleep deprivation device for 18 h (7 a.m. to 1 a.m.) daily for 21 days. Weight gain, food intake, the electrical power of orexin neurons, CB1R mRNA expression in hypothalamus, CB1R protein expression in the LH, TNF-α, IL-6, IL-4 levels and antioxidant activity in hypothalamus were measured after SD induction. Our results showed that AEA administration significantly improved food intake (p < 0.01), Electrical activity of orexin neurons (p < 0.05), CB1R expression in the hypothalamus (p < 0.05), and IL-4 levels (p < 0.05). AEA also reduced mRNA expression of OX1R and OX2R (p < 0.01 and p < 0.05 respectively), also IL-6 and TNF-α (p < 0.01) and MDA level (p < 0.05) in hypothalamic tissue. As a consequence, AEA modulates orexinergic system function and improves food intake by regulating the expression of the CB1 receptor in the LH in sleep deprived rats.

Neuroprotective effect of anethole against rotenone induced non-motor deficits and oxidative stress in rat model of Parkinson's disease.

INTRODUCTION: Non-motor symptoms (NMS) have high prevalence in patients with Parkinson's disease (PD). These symptoms are mainly the result of increased oxidative stress and neuronal damage. In this study we investigated the possible neuroprotective effects of anethole as a potent antioxidant on rotenone-induced behavioral deficits, hippocampal neuronal death, and oxidative stress profile in rats. METHODS: Male Wistar rats were administered with anethole (62.5, 125, and 250 mg/kg, i.g) concomitantly with rotenone (2 mg/kg, s.c) for 35 days. Shuttle box and novel object recognition tests were performed to determine cognitive functions, and tail flick test was used to measure pain sensitivity. The levels of BDNF, MDA, SOD, and GPx were assayed in the hippocampus. Hippocampal neuronal damage was evaluated using cresyl violet staining technique. RESULTS: Chronic administration of rotenone induced cognitive deficit and reduced thermal pain threshold. Rotenone also decreased SOD and GPx activities, increased MDA level, and reduced the expression of BDNF in the hippocampus. In addition, hippocampal neuronal loss was increased in rotenone treated rats. Treatment with high dose of anethole (250 mg/kg) improved cognitive function and increased pain threshold in all three doses (62.5, 125, and 250 mg/kg). Despite the unchanged SOD and GPx activities, hippocampal levels of MDA was significantly decreased after high-dose anethole treatment. Moreover, High dose of anethole increased the number of surviving neurons in the hippocampus, but couldn't increase the BDNF expression. CONCLUSION: Our findings indicated that anethole has antioxidant and neuroprotective effects against non-motor disorders induced by rotenone toxicity.

Protective Effects of Co-administration of Zinc and Selenium Against Streptozotocin-Induced Alzheimer's Disease: Behavioral, Mitochondrial Oxidative Stress, and GPR39 Expression Alterations in Rats.

Changes in the concentrations of trace metals such as zinc (Zn) and selenium (Se) can pathologically lead to neurodegenerative conditions such as the Alzheimer's disease (AD). Previous studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of AD. Several male Wistar rats were randomly divided into five groups: sham group, AD group that received 3 mg/kg of streptozotocin (STZ) intracerebroventricularly, AD + Zn group that received 10 mg/kg of Zn intraperitoneally (i.p.) for 1 week, AD + Se group that received 0.1 mg/kg of Se i.p. for 1 week, and AD + Zn + Se group that received 10 mg/kg of Zn i.p. plus 0.1 mg/kg of Se i.p. for 1 week. At end of the study, behavioral tests and mitochondrial oxidative stress and GPR39 gene expression evaluations were carried out. Co-administration of Zn and Se significantly decreased the potential collapse of mitochondrial membrane, reactive oxygen species levels, and lipid peroxidation levels while significantly increased cognitive performance, superoxide dismutase (SOD), glutathione peroxidase, and catalase activity in the brain mitochondria compared with the STZ group. In addition, no significant changes were observed in GPR39 expression in the co-treated group. Findings of the current study showed that ZnR/GPR39 receptor, mitochondrial dysfunction, and oxidative stress play important roles in the pathogenesis of AD. Co-treatment of Zn and Se improved the cognitive performance, mitochondrial dysfunction, and oxidative stress caused by STZ-induced AD. Therefore, therapeutic approaches to improve mitochondrial function could be effective in preventing the initiation and progression of AD.

Aloe vera gel improves behavioral deficits and oxidative status in streptozotocin-induced diabetic rats.

Oxidative stress has a major role in progression of diabetes-related behavioral deficits. It has been suggested that Aloe vera has anti-diabetic, antioxidative, and neuroprotective effects. The present study was designed to determine the effects of Aloe vera gel on behavioral functions, oxidative status, and neuronal viability in the hippocampus of streptozotocin (STZ)-induced diabetic rats. Fifty five adult male Wistar rats were randomly divided into five groups, including: control (normal saline 8ml/kg/day; P.O.), diabetic (normal saline 8ml/kg/day; P.O.), Aloe vera gel (100mg/kg/day; P.O.), diabetic+Aloe vera gel (100mg/kg/day; P.O.) and diabetic+NPH insulin (10 IU/kg/day; S.C.). All treatments were started immediately following confirmation of diabetes in diabetic groups and were continued for eight weeks. Behavioral functions were evaluated by employing standard behavioral paradigms. Additionally, oxidative status and neuronal viability were assessed in the hippocampus. The results of behavioral tests showed that diabetes enhanced anxiety/depression-like behaviors, reduced exploratory and locomotor activities, decreased memory performance, and increased stress related behaviors. These changes in diabetic rats were accompanied by increasing oxidative stress and neuronal loss in the hippocampus. Interestingly, eight weeks of treatment with Aloe vera gel not only alleviated all the mentioned deficits related to diabetes, but in some aspects, it was even more effective than insulin. In conclusion, the results suggest that both interrelated hypoglycemic and antioxidative properties of Aloe vera gel are possible mechanisms that improve behavioral deficits and protect hippocampal neurons in diabetic animals.