VITAL STRESS INDUCED BY PREDATOR EXPOSURE CAUSES DISRUPTIONS IN FEEDING BEHAVIOR AND ACTIVATION OF PRO-INFLAMMATORY MARKERS IN THE HYPOTHALAMUS OF RATS

BACKGROUND: Stress is a major risk factor for the development of psychoneurological disorders, including eating disorders. One of the key mediators of the stress response is ghrelin, a hormone involved in the regulation of feeding behavior and neuroinflammatory processes. Investigating its role in the formation of stress-associated dysfunctions and microglial activation opens new perspectives for understanding the pathogenesis of psychiatric disorders and developing effective therapeutic strategies.

AIM: To study the effect of acute traumatic stress caused by predator exposure on desacyl-ghrelin levels in the hypothalamus, microglial activity, and feeding behavior in rats.

MATERIALS AND METHODS: The experiment was conducted using a predator exposure stress model. Animals were subjected to a traumatic stimulus, after which their feeding behavior was assessed using a compulsive overeating model. The desacyl-ghrelin content in the hypothalamus was measured using a high-sensitivity ELISA. Microglial activation was evaluated via immunohistochemical staining for the calcium-binding protein Iba-1, while the expression level of the Tlr4 gene in the hypothalamus was determined using reverse transcription PCR (RT-PCR).

RESULTS: Predator exposure stress led to a significant reduction in the consumption of both standard chow and high-calorie food in rats. Additionally, a six-fold decrease in desacyl-ghrelin concentration in the hypothalamus was observed in stressed animals compared to the control group, along with a two-fold increase in Tlr4 gene expression. Immunohistochemical analysis revealed focal microglial activation in the hypothalamus of rats that had undergone predator exposure stress.

CONCLUSIONS: Acute predator exposure stress is accompanied by a significant reduction in desacyl-ghrelin levels in the hypothalamus, an increase in Tlr4 gene expression, and microglial activation, indicating the involvement of inflammatory mechanisms in the stress response. Additionally, it was established that stress induces changes in feeding behavior, reducing the intake of both standard and high-calorie food, which may indicate a disruption in adaptive mechanisms. The decrease in ghrelin levels under stress may trigger a cascade of immune reactions, including microglial activation, which in turn contributes to the development of local neuroinflammation and structural damage in the brain. These processes may underlie the formation of stress-associated psychoneurological disorders.