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.