Investigation of the effects of intracerebroventricularly administered Nesfatin-1 on the amygdala and hypothalamic-pituitary-adrenal axis

Nesfatin-1 is expressed in neurons related to appetite control in the hypothalamus and is known for its anorexigenic (appetite-suppressing) effect. Additionally, it has been suggested that Nesfatin-1 may regulate stress-related behaviors. During the stress response, Nesfatin-1 activates serotonergic and noradrenergic neurons, enhancing the activity of the hypothalamic-pituitary-adrenal (HPA) axis. Nesfatin-1 interacts with kisspeptin, corticotropin-releasing hormone (CRH), and oxytocin receptors. In this study, adult male Wistar albino rats were divided into six groups. The experimental groups were planned as control, Nesfatin-1, Nesfatin-1+p234, Nesfatin-1+Antalarmin, Nesfatin-1+Astressin2B and Nesfatin-1+Atosiban. Thirty minutes after the injection into the lateral ventricle under anesthesia, the rats were sacrificed. Amygdala norepinephrine and dopamine levels were measured using HPLC, while glutamate, gamma-aminobutyric acid (GABA), serotonin levels and serum corticosterone were measured using ELISA. Brain sections were taken for immunohistochemical analysis. The results were evaluated using one-way ANOVA and Tukey's test. In the Nesfatin-1 and Nesfatin-1+p234 groups, CRH immunoreactivity in the paraventricular nucleus, amygdala norepinephrine levels, serum adrenocorticotropic hormone and corticosterone levels were found to be significantly higher compared to the control group (p<0.05). Additionally, the GABA and dopamine levels in the amygdala of these groups, along with the Nesfatin-1+Atosiban group, were significantly lower than in the control group (p<0.05). No statistically significant differences were found in amygdala glutamate and pituitary oxytocin levels (p>0.05). Serotonin levels was significantly lower only in the Nesfatin-1+p234 group compared to the control group (p<0.05). Our results indicate that Nesfatin-1 activates the HPA axis and stimulates the amygdala. Additionally, Nesfatin-1 enhances HPA axis activity even when kisspeptin signaling is impaired. It was also found that the reduction of serotonin and GABA levels in the amygdala plays a role in these Nesfatin-1-induced effects. Keywords: Adrenal Gland, Amygdala, Hypothalamus, Nesfatin-1, Pituitary Gland