PT - JOURNAL ARTICLE AU - Sierra A. Codeluppi AU - Dipashree Chatterjee AU - Thomas D. Prevot AU - Keith A. Misquitta AU - Etienne Sibille AU - Mounira Banasr TI - Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex AID - 10.1101/2021.02.23.432559 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.02.23.432559 4099 - http://biorxiv.org/content/early/2021/02/24/2021.02.23.432559.short 4100 - http://biorxiv.org/content/early/2021/02/24/2021.02.23.432559.full 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 behavioral effects on anhedonia- and anxiety-like behaviours 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 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. Additionally, the number of intersections at the most distal radius step significantly correlated with time spent in the shelter zone in the PhenoTyper test (r=-0.581, p<0.01) for GFP+ cells and with behavioural emotionality calculated by z-scoring all behavioral measured deficits, for both GFAP+ and GFP+ cells (r=-0.400, p<0.05; r=-0.399, p<0.05).Conclusion Chronic stress exposure induces a progressive atrophy of cortical astroglial cells, potentially contributing to maladaptive neuroplastic changes associated with stress-related disorders.Competing Interest StatementThe authors have declared no competing interest.