Acute systemic inflammation induces region-specific morphological remodeling of astrocytes and microglia concurrent...

Neuroinflammation is recognized as a key mechanism underlying depression, with glial cells playing a central role in regulating neuronal activity and neuroimmune interactions. However, how microglia and astrocytes in distinct brain regions respond morphologically to peripheral inflammatory stimulation and how these changes contribute to depression remain poorly understood. Here, we established a lipopolysaccharide (LPS)-induced mouse model of inflammation-related depression and observed a significant increase in c-Fos expression in emotion- and stress-related brain regions, including the bed nucleus of the stria terminalis (BST), the paraventricular nucleus of hypothalamus (PVN), the ventrolateral periaqueductal gray (vlPAG), the locus coeruleus (LC) and the solitary nucleus (Sol). Using three-dimensional (3D) reconstruction and Sholl analysis, we quantified the process complexity, spatial coverage and filamentous architecture of both microglia and astrocytes. Microglia showed hypertrophy across all examined regions. BST and PVN exhibited thicker and straighter processes, LC and vlPAG displayed decreased spatial complexity, and Sol exhibited reactive hypertrophy characterized by increased filament volume and maximal intersections. Astrocytes generally exhibited reduced filament length, process diameter, or structural simplification in the BST, PVN, LC and vlPAG, whereas Sol astrocytes displayed increased process diameter but reduced filament length, area and maximal radius. Together, these findings provide a structural basis for understanding the cellular mechanisms underlying inflammation-related depression across different brain regions and suggest potential functional roles of glial remodeling in inflammatory depression.