RT Journal Article SR Electronic T1 Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.02.23.432559 DO 10.1101/2021.02.23.432559 A1 Sierra A. Codeluppi A1 Dipashree Chatterjee A1 Thomas D. Prevot A1 Yashika Bansal A1 Keith A. Misquitta A1 Etienne Sibille A1 Mounira Banasr YR 2021 UL http://biorxiv.org/content/early/2021/06/08/2021.02.23.432559.abstract AB Background Neuromorphological changes are consistently reported in the prefrontal cortex (PFC) of patients with stress-related disorders and in rodent stress models, but the effects of stress on astrocyte morphology and potential link to behavioral deficits are relatively unknown.Methods To answer these questions, transgenic mice expressing green fluorescent protein (GFP) under the glial fibrillary acid protein (GFAP) promotor were subjected to 7, 21 or 35 days of chronic restraint stress (CRS). CRS induced behavioral effects on anhedonia- and anxiety-like behaviors were measured using the sucrose intake and the PhenoTyper tests, respectively. PFC GFP+ or GFAP+ cells morphology was assessed using Sholl analysis and associations with behavior were determined using correlation analysis.Results CRS-exposed male and female mice displayed anxiety-like behavior at 7, 21 and 35 days and anhedonia-like behavior at 35 days. Analysis of GFAP+ cell morphology revealed significant atrophy of distal processes following 21 and 35 days of CRS. CRS induced similar decreases in intersections at distal radii for GFP+ cells, accompanied by increased proximal processes. In males, the number of intersections at the most distal radius step significantly correlated with anhedonia-like behavior (r=0.622, p<0.05) for GFP+ cells and with behavioral emotionality calculated by z-scoring all behavioral measured deficits (r=-0.667, p<0.05). Similar but not significant correlations were observed in females. No correlation between GFP+ cell atrophy with anxiety-like behavior was found.Conclusion Chronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic and behavioral changes associated with stress-related disorders.Competing Interest StatementThe authors have declared no competing interest.