Involvement of perineuronal nets in anti-depressant effects of electroacupuncture in chronic-stress-induced depression in rats

Abstract Acupuncture help alleviate depression-like behaviors, but the neural mechanisms behind such anti-depressive impacts are still unknown. Abnormalities in the perineuronal net (PNN) have been documented in multiple psychiatric disorders. The modulation and neural mechanism of PNNs in the antidepressant process of electroacupuncture (EA) at Baihui (GV20) and Yintang (GV29) points were investigated in this work. A rat depression model was induced by chronic unpredicted mild stress (CUMS). Acupuncture was performed on model rats in the EA group at GV20 and GV29 acupoints every other day for 30 min each time. The fluoxetine (FLX) group of model rats were gavaged with 10 mg/kg fluoxetine each day. Immunohistochemistry and western blot assays were used to evaluate the density and components of PNNs, the protein expression levels of the main synthase of GABA, GAD67, and of the synaptic proteins GLuA1, and PSD95 in the pre-limbic (PrL) and sub-limbic (IL) of mPFC. We found that four weeks of CUMS could decrease the levels of PNN component proteins aggrecan and brevican and GAD67. Electroacupuncture exhibited significant anti-depressive effects on depressive rats by altering the levels of PNNs. Specifically, aggrecan and brevican are involved in the anti-depression mechanism of electroacupuncture. After electroacupuncture treatment, the decreased expression of GAD67, GLuA1 and PSD95 in the mPFC induced by CUMS for four weeks was also reversed. This indicates that the mechanism of acupuncture's antidepressant effect may be based on reversing the stress-induced decline in PNN expression, the functional impairment of GABA neurons, and the regulation of excitatory synaptic expression.