Abstract

Background: Converging evidence indicates that the glutamatergic system and glia are directly implicated in the pathophysiology of depression. Clinical studies indicate that electroacupuncture (EA) has anti-depressant-like effects with low side effects for depression. However, the underlying antidepressant mechanism of acupuncture remains obscure.

Methods: Chronic unpredictable mild stress (CUMS)-induced depressive rats were used to induce depressive-like behavior and evaluated by the weight change, open field test, sucrose preference test, and novelty suppressed feeding test. EA, NMDA receptor subunit 2A antagonist (NR2A RA) or NMDA receptor subunit 2B antagonist (NR2B RA) was used for comparison. Highperformance liquid chromatography (HPLC) was performed to detect the content of hippocampal glutamate, while western blot was performed for the hippocampal protein expression levels of calcium/calmodulin-dependent protein kinase II (CaMKII), Bax, caspase 3 and B-cell lymphoma-2 (Bcl-2). The distribution of glutamate ionotropic receptor NMDA type subunit 2A (NR2A), neuronal nuclear protein (NeuN), glutamate ionotropic receptor NMDA type subunit 2B (NR2B), and glial fibrillary acidic protein (GFAP) were detected by immunofluorescence.

Results: Significant depression behavior (reduced body weight and sucrose preference, increased feeding and immobility time) was produced in CUMS-induced depressive rats, which was reversed significantly by EA. EA decreased hippocampal glutamate level. EA led to a significant decrease in expression levels of Bax, caspase 3, and CaMK II accompanied by increased Bcl-2 expression levels. Furthermore, EA significantly increased NR2A expression level as well as decreased NR2B expression level in the hippocampus.

Conclusion: EA ameliorated depression-like behavior in CUMS rats, which might be mediated, at least in part, by regulating the glutamate, NMDA receptors, and apoptosis in the hippocampus.

Keywords: Depression, glutamate, NMDA, astrocyte, apoptosis, hippocampus, chronic unpredictable mild stress, electroacupuncture.