Electroacupuncture Reverses CUMS-Induced Depression-Like Behaviors and LTP Impairment in Hippocampus by Downregulating NR2B and CaMK II Expression.

Shuo Jiang,Wenlin Xu,Zhaohui Liang,Zui Shen

doi:10.1155/2021/9639131

Abstract

Objective Depression is a global mental health problem with high disability rate, which brings a huge disease burden to the world. Electroacupuncture (EA) has been shown to be an effective method for the treatment of depression. However, the mechanism underling the antidepressant effect of EA has not been clearly clarified. The change of synaptic plasticity is the focus in the study of antidepressant mechanism. This study will observe the effect of EA on LTP of hippocampal synaptic plasticity and explore its possible mechanism. Methods The depression-like behavior rat model was established by chronic unpredictable mild stress (CUMS). EA stimulation (Hegu and Taichong) was used to treat the depressed rats. The depression-like behavior of rats was tested by weight measurement, open field test, depression preference test, and novelty suppressed feeding test. Long-term potentiation (LTP) was recorded at CA1 synapses in hippocampal slices by electrophysiological method. N-methyl-D-aspartate receptor subunit 2B (NR2B) and calmodulin-dependent protein kinase II (CaMK II) protein levels were examined by using western blot. Results After the establishment of CUMS-induced depression model, the weight gain rate, sucrose preference rate, line crossing number, and rearing times of rats decreased, and feeding time increased. At the same time, the LTP in hippocampus was impaired, and the expressions of NR2B and CaMK II were upregulated. After EA treatment, the depression-like behavior of rats was improved, the impairment of LTP was reversed, and the expression levels of NR2B and CaMK II protein were downregulated. Conclusion EA can ameliorate depression-like behaviors by restoring LTP induction, downregulating NR2B and CaMK II expression in CUMS model rats, which might be part of the mechanism of EA antidepressant.

Highlights

Depression is a major global mental health problem with high prevalence, recurrence rate, disability rate, and suicide risk
We found that chronic unpredictable mild stress (CUMS) can lead to the overactivation of postsynaptic glutamate NMDA pathway in rat hippocampal astrocytes, resulting in the accumulation of glutamate and a large amount of Ca2+ flowing into neurons and astrocytes, resulting in intracellular calcium overload
We explored the antidepressant effect of electroacupuncture and its possible mechanism by studying the effects of EA on hippocampal synaptic plasticity and N-methyl-D-aspartate receptor subunit 2B (NR2B) protein level in CUMS rat models

Summary

Introduction

Depression is a major global mental health problem with high prevalence, recurrence rate, disability rate, and suicide risk. Depression has become the main cause of disability in the world and the second largest disease burden after ischemic heart disease [2,3]. E pathogenesis of depression is complex and unclear. The pathogenesis of depression is diverse, such as the regulation of monoamine neurotransmitters and their receptors in the brain, neuroendocrine disorders, neurotrophin malnutrition and nerve regeneration, changes in hippocampal neurons, cell signal transduction, and immune function [5]. Neural plasticity has gradually become a research hotspot [6,7,8,9]. As the embodiment of system reorganization, neural plasticity continues through the normal development, maturation, and degradation of the nervous system.

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Results

Conclusion