HETEROGENEOUS MICROGLIAL REMODELING IN AMYGDALA AND HABENULA UNDER DIVERSE STRESS PARADIGMS: ACUTE, CHRONIC, AND SOCIAL DEFEAT STRESS

Stress exposure can lead to emotional dysregulation and thus to the development of stress-related neuropsychiatric disorders such as posttraumatic stress disorder or depression. To address neurobiological changes, microglial responses in the Amygdala and Habenula—two key structures involved in emotional regulation and stress processing were assessed. C57BL6J male mice were exposed to three stress paradigms: Acute Restraint Stress (AS), Chronic Restraint Stress (CS) and Chronic Social Defeat Stress (SDS). After the protocol, mice brains were adequately collected and immunoassayed against microglial Iba1. Microglial cells from Basolateral (BLA) and Central Amygdala (CeA); Lateral (LHb) and Medial Habenula (MHb) were assessed using an ImageJ-FIJI macro which quantified microglial soma and total Iba1 area as a proxy of microglial reactivity. Furthermore, microglial processes area could be inferred mathematically from these variables. Microglial responses varied with stress type and brain region. CeA microglia was the most reactive to the three paradigms showcasing different microglia reactions according to the stressor. Both CS and SDS produced an increase in soma size, however while CS reduced the area associated with processes in the microglia, SDS increased it. Although milder, this increase in area of processes was also observed under AS. On the contrary, only Habenular microglia from MHb reacted more robustly under CS, with a decreased in soma circularity and area of processes. A cluster analysis further revealed distinct remodeling between Amygdala and Habenular subregions. This heterogeneous microglial response indicates the importance of stressor nature and specific anatomical context when studying stress-related conditions.