Differential effects of acute, chronic, and social defeat stress on microglial morphology in the basolateral and central amygdala, and the medial and lateral habenula

Abstract

Effective stress regulation is essential for emotional health, whereas maladaptive stress responses contribute to neuropsychiatric disorders such as depression and post-traumatic stress disorder. Because neuron–microglia interactions are increasingly recognized as key modulators of neuroplasticity under physiological conditions, stress-related microglial dysregulation may contribute to aberrant neuronal responses implicated in mental health disorders. This exploratory study examined region-specific microglial morphometric responses to acute intense stress, chronic restraint stress, and social defeat stress (SDS) in the amygdala and habenula, focusing on the BLA, CeA, LHb, and MHb. Microglial morphology was assessed using animal-level morphometric comparisons and exploratory cluster-based profiling. Acute stress was associated with limited animal-level morphometric differences, while exploratory cluster distributions suggested subregion-dependent shifts, particularly in the CeA and LHb. Chronic stress was associated with larger soma-related parameters in the BLA and CeA, together with a descriptive redistribution toward large-soma/low-process profiles in both amygdalar subregions. In the habenula, chronic stress induced selective MHb morphometric changes, while cluster profiles remained comparatively constrained. SDS was associated with the most pronounced remodelling in the amygdala, including increased soma-related measures, reduced circularity/solidity in the CeA, altered spatial organization, and a strong redistribution toward large-soma/ high-process profile. SDS also shifted LHb cluster profiles, whereas the MHb showed comparatively limited sensitivity. Overall, these exploratory findings suggest that different stressors are associated with region- and subregion-dependent microglial remodelling, with the amygdala showing greater stress-related plasticity than the habenula. These patterns support further investigation of microglial morphological adaptation as a potential contributor to stress-related psychopathology.