Chronic Stress Alters Astrocyte Morphology in Mouse Prefrontal Cortex

Abstract

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.

Positive effects of running exercise on astrocytes in the medial prefrontal cortex in an animal model of depression

“…Albert and Newhouse found that antidepressant therapies in females are affected by estrogen levels (Albert & Newhouse, 2019). (Codeluppi et al, 2021) reported that the behavior changes induced by CRS are sex-specific and that the changes might be related to the stage of the estrus cycle. Furthermore, there are sex differences in the effects of exercise on both brain structures and behavioral tasks (Martini et al, 2022).…”

Human Astrocyte Spheroids as Suitable In Vitro Screening Model to Evaluate Synthetic Cannabinoid MAM2201-Induced Effects on CNS

“…It is important to consider the role that astrocyte-induced plasticity may be playing in the behavioral sequelae of insults, such as stressors or neurotransmitters (endogenous or exogenous—e.g., synthetic drugs), which, through their receptors located in astrocytes, directly induce intracellular cascades. The latter ultimately introduces changes in the morphology/physiology of astrocytes that alters the normal functioning of tripartite synapses in a pathophysiological direction that is known to drive behavioral sequelae [ 53 , 55 ].…”

“…An increasing number of reports have indicated that chronic and acute stressors alter astrocyte morphology and the expression of astrocyte-specific proteins in brain areas that are known to play a critical role in emotional processing, such as the prefrontal cortex, hippocampus, and amygdala [ 53 , 54 , 55 ].…”

Encore: Behavioural animal models of stress, depression and mood disorders

“…Longer sessions of 24 h induce depressive-like behaviours for more than a month, which are reversible by fluoxetine administration ( Chu et al, 2016 ). Anxiety-like behaviours emerge after 1 week of stress, whereas anhedonic behaviours emerge after 5 weeks of stress ( Codeluppi et al, 2021 ). It has been reported that CRS and CSDS induce similar changes in anhedonic, social-avoidant, and immobile behaviour ( Haenisch et al, 2009 ; Veena et al, 2009 ; Ulloa et al, 2010 ; Voorhees et al, 2013 ; Mao et al, 2022 ).…”