The Role Of Chronic Stress In Remodeling Astrocytic Network In The Basolateral Amygdala

Continuous exposure to stressful environment is one of the key causes of a series of neuropsychiatric diseases,including anxiety disorder and depression.As the core brain regions for emotion expression and regulation,amygdala plays an important role in mediating the adversities by stress.A lot of research shows that chronic stress can cause a series of emotional and behavioral disorders via remolding the structure and function of amygdala neurons.However,in addition to neurons,very few studies have explored the influence of stress on other cell types in amygdala,as well as the mechanism and pathological effect.Clearly,it is of great value to reveal the role of these cell types in stress-induced mental diseases and the underlying mechanisms,which will help to understanding the pathogenesis of related diseases and develop new clinical prevention and treatment strategies.Astrocytes are distributed throughout the central nervous system.Multiple astrocytes are organized into an interconnected network through gap junction,which represents one of the important characteristics which distinguishes these cells from other ones.A lot of research has shown that this network connection plays an important role in regulating neuronal activity,synaptic plasticity and behavior.More and more clinical and preclinical evidence has shown that stress exposure and development of stressrelated diseases can cause changes in astrocytic network.For example,in the frontal cortex of depressed patients,the expression of connexin 30(CX30)and connexin 43(Cx43)that mediates astrocyte coupling is downregulated.However,it is unclear how chronic stress exposure affects the astrocytic coupling in amygdala and what mechanisms account for the effect of stress exposure.To answer the above questions,in this study,we used C57bl/6j mice in the early adult stage to make two chronic stress models,namely,chronic unpredictable stress(CUS),chronic restraint stress(CRS).The effects of chronic stress exposure on the astrocytic network were explored in the basolateral region of amygdala(BLA)and the possible mechanisms were also discussed.The results showed that CUS and CRS effectively reduced the structural coupling of astrocytes in the BLA.Further analysis showed that the reduced connection was prominent in the anterior,intermediate and posterior the BLA,suggesting no subregion-specificity of stress influence.We then used RT-PCR to test the effect of chronic stress on the expression of the gene associated with coupling among the BLA astrocytes.The results showed that CUS and CRS significantly reduced the m RNA level of Cx43 in the BLA,while the transcription levels of CX30 and Sox9 remained unaltered.Finally,we used pharmacological approach to inhibit the synthesis of corticosterone or the activation of glucocorticoid receptor and found that they both effectively reversed the damage of chronic stress on the astrocytic network of the BLA.By contrast,inhibition of corticosteroid receptor had little effect.These results suggest that chronic stress lower the expression of Cx43 in astrocytes and damage the coupling of astrocytes in the BLA through activating glucocorticoid receptor signaling.The current study provides new experimental evidence for the understanding of neuronal and molecular mechanism underlying the influence of chronic stress on amygdala function,and provides potential intervention targets for the prevention and treatment of stress-related mood and emotional disorders.