Running Exercise Promotes Astrocyte-Mediated Structural Plasticity in the Amygdalar BLA and CeA to Alleviate Anhedonia-like Behavior Alterations

Amygdala dysfunction is implicated in stress-related affective disorders, and astrocytes are key regulators of amygdalar neuroplasticity. Here, we examined whether running exercise modulates astrocyte number, morphology, proliferation, and excitatory synaptic contacts in the basolateral amygdala (BLA) and central amygdala (CeA) in rats exposed to chronic unpredictable stress (CUS). Anhedonia-like behaviors were evaluated using the sucrose preference test, while anxiety-related behaviors were assessed using the elevated plus maze and open field tests. Unbiased stereological three-dimensional quantification was used to assess amygdalar volume and estimate astrocyte numbers in BLA and CeA, and immunofluorescence with morphological reconstruction was performed to quantify astrocytic complexity, proliferation, and astrocyte-associated PSD95+ puncta. Running exercise significantly increased sucrose preference in CUS rats, whereas elevated plus maze and open field measures were not significantly changed. CUS reduced astrocyte number and proliferation, and induced astrocytic morphological atrophy in both subregions. These alterations were reversed by running. Moreover, running increased the number of excitatory synapses contacted by astrocytes in the BLA and CeA of CUS rats. These findings suggest that running promotes astrocyte-mediated structural remodeling in amygdalar subregions, which may contribute to the regulation of anhedonia-like behavioral alterations associated with chronic stress.