234. ANXIETY BEHAVIOR AND IMMUNE RESPONSE OF MICROGLIA IN RATS SUBJECTED TO STRESS THROUGH THE SYMPATHETIC NERVOUS SYSTEM

Abstract Background Psychological stress has various effects, including changes in eating behavior, anxiety-like behavior, and depression-like behavior. Recently, the relationship between immune cells, particularly microglia (MG), and anxiety behaviors has been reported. Stress has also been shown to activate MG and macrophages. Stress responses can be broadly categorized into the humoral pathway involving the hypothalamic-pituitary-adrenal (HPA) axis and the neural pathway involving the sympathetic nervous system (SNS). The HPA axis exhibits a slower response from stimulus input to output compared to the SNS. The SNS, mediated by norepinephrine (NA), reacts within a very short time frame. Aims & Objectives To analyze the changes in anxiety-related behaviors and MG immune responses to stress mediated by the SNS. Method Behavioral experiments were conducted using Wistar rats. The rats were intraperitoneally administered saline (CTRL), phenylephrine (PE, 50 μg/kg), isoproterenol (ISO, 50 μg/kg), or propranolol (PROP, 10 mg/kg). Ten minutes after administration, the activity levels were compared over a 20-minute period. In the open field test (OFT), parameters such as activity distance, activity time, activity speed, and behavior patterns were measured. Following perfusion fixation, the brains were extracted, and morphological changes in MG were observed. Analyses were performed using immunohistochemistry, in-situ hybridization, and fluorescent immunohistochemistry. All procedures adhered to the animal experiment guidelines of the International University of Health and Welfare, aiming to minimize the number of animals used and their distress. Statistical analysis was conducted using SPSS (one-way ANOVA), and image analysis was performed using Image J. Results Compared to the CTRL group, PE, ISO, and PROP administration showed a tendency to reduce activity levels in rats. PE and ISO induced widespread MG activation in the brain, whereas PROP demonstrated MG suppression. In the locus coeruleus (LC), PE and ISO significantly increased TH, c-Fos, and TH mRNA levels, while PROP resulted in unchanged or decreased levels of these markers. Discussion & Conclusions The results indicate that MG activation occurs via SNS agonists and that these agonists induce behavioral suppression and anxiety-like behavior patterns. Thus, a significant correlation is suggested between MG responses mediated by the SNS and anxiety-related behaviors.