Sex-dependent and region-specific morphological adaptations in astrocytes following early-life stress

Astrocytes exhibit structural variation, with cell shape offering a useful metric of experience-based adaptability. However, comprehensive single-cell mapping, capturing whole cellular domains, remains difficult to compare across brain areas and experimental groups. Researchers employed unilateral retro-orbital administration of PHP.eB-GfaABC1D-eGFP as a straightforward approach for selective astrocyte tagging and examined regional, gender, and early-life-stress variations in the mouse amygdala.

Systemic viral injection targeting astrocytes throughout the brain resulted in eGFP-positive cells prominently distributed in cortex, hippocampus, hypothalamus, and amygdala. For naive females, lateral and basal amygdala astrocytes displayed similar morphological traits. In naive males, basal amygdala astrocytes were larger in volume and possessed a smaller surface-area-to-volume ratio, while surface area, soma diameter, territory, and arborization measures did not differ significantly.

Remarkably, early-life stress triggered sex-specific morphological reactions in the basal amygdala. Females exhibited an increase in perimeter, area, and Feret diameter, without substantial alterations in three-dimensional volume or detailed filament analysis. Conversely, males experienced a reduction in surface area and volume, without notable changes in projected territorial dimensions, soma diameter, or detailed filament measures.

The density of S100β-positive cells remained constant across the different regional and stress comparisons. These results demonstrate that the utilized method is a practical and effective way to measure astrocyte morphology and uncover a sex-dependent and region-specific dissociation between territorial expansion and overall volumetric contraction following early-life stress.