Abstract
Previous studies have indicated that impaired synaptic plasticity is a main pathological alteration in depression. However, the mechanism underlying this pathological change has not been clarified. Adiponectin, an adipokines, crosses the blood-brain barrier to function in special brain regions. Previous studies have suggested that the downregulation of adiponectin signaling is involved in the occurrence of depression. Adiponectin receptors (AdipoRs), AdipoR1 and AdipoR2, which serves as the main receptors for adiponectin in the central nervous system, mediate the downstream biological effects of this compound, which has been reported to have positive effects on synaptic plasticity. However, it is not clear whether alternations in adiponectin/AdipoRs signaling are associated with impaired synaptic plasticity in depression. Therefore, the aim of this study was to investigate whether changes in the adiponectin/AdipoRs pathway in the hippocampus during depression are involved in the regulation of synaptic plasticity damage. We detected reduced plasma concentrations of adiponectin and lower expression levels of AdipoR1 but not of AdipoR2 in the hippocampus in mice exposed to the chronic unpredictable stress. Then, an adeno-associated virus was used to knockdown hippocampal AdipoR1 to further verify the effects of decreased expression levels of this receptor on depressive-like behaviors and hippocampal synaptic plasticity. We found that the mice in which hippocampal AdipoR1 was knocked down presented with anhedonia and passive stress-coping behaviors as well as a decreased number of dendritic spines and density of excitatory and inhibitory synapses. Our results suggest that the downregulation of AdipoR1 expression might be an important factor that causes impaired synaptic plasticity in depression. These results may provide new insights into the pathogenesis of depression and new therapeutic targets or treating the disease.