Eating behavior disorders and activation of pro-inflammatory markers in the hypothalamus of rats induced by predator exposure stress

Background: Stress is a major risk factor for the development of neuropsychiatric disorders, including eating behavior disorders. One of the key mediators of the stress response is ghrelin, a hormone involved in the regulation of eating behavior and neuroinflammatory processes. Investigation of its role in stress-associated disorders and microglial activation offers new perspectives for understanding the pathogenesis of mental disorders and for developing effective therapeutic strategies.

Aim: The work aimed to examine the effects of acute traumatic predator exposure stress on hypothalamic desacyl ghrelin levels, microglial activity, and eating behavior in rats.

Methods: The experiment was conducted using a predator exposure stress model. Animals were subjected to a traumatic stimulus, after which their eating behavior was assessed in a compulsive overeating model. Hypothalamic desacyl ghrelin levels were measured using a highly sensitive enzyme-linked immunosorbent assay. Microglial activation was assessed via immunohistochemical detection of the calcium-binding protein ionized calcium-binding adapter molecule 1 (Iba-1). Hypothalamic Tlr4 gene expression was evaluated using reverse transcription–polymerase chain reaction.

Results: Predator exposure stress significantly reduced the intake of both standard chow and high-calorie food in rats. In addition, a marked decrease in hypothalamic desacyl ghrelin concentration was observed (sixfold lower compared with the control group), along with a twofold increase in Tlr4 gene expression. Immunohistochemical analysis revealed focal microglial activation in the hypothalamus of stressed animals.

Conclusion: Acute predator exposure stress was associated with a substantial reduction in hypothalamic desacyl ghrelin levels, elevated Tlr4 gene expression, and microglial activation, indicating the involvement of inflammatory mechanisms in the stress response. Stress was shown to alter eating behavior by decreasing consumption of both standard chow and high-calorie food, which may reflect impaired adaptive mechanisms. Stress-induced ghrelin reduction may initiate a cascade of immune reactions, including microglial activation, which in turn can contribute to local neuroinflammation and damage to brain structures. These processes may underlie the development of stress-associated neuropsychiatric disorders.