Oncotarget

Research Papers:

GABAergic neurons in nucleus accumbens are correlated to resilience and vulnerability to chronic stress for major depression

Zhaoming Zhu, Guangyan Wang, Ke Ma, Shan Cui and Jin-Hui Wang _

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Oncotarget. 2017; 8:35933-35945. https://doi.org/10.18632/oncotarget.16411

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Abstract

Zhaoming Zhu1,*, Guangyan Wang1,*, Ke Ma1,*, Shan Cui2, Jin-Hui Wang1,2,3

1Qingdao University, School of Pharmacy, Qingdao Shandong, 266021, China

2State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China

3University of Chinese Academy of Sciences, Beijing, 100049, China

*These authors contributed equally to this work

Correspondence to:

Jin-Hui Wang, email: jhw@sun5.ibp.ac.cn

Keywords: depression, resilience, neuron, synapse, nucleus accumbens

Received: February 18, 2017     Accepted: March 14, 2017     Published: March 21, 2017

ABSTRACT

Background: Major depression, persistent low mood, is one of common psychiatric diseases. Chronic stressful life is believed to be a major risk factor that leads to dysfunctions of the limbic system. However, a large number of the individuals with experiencing chronic stress do not suffer from major depression, called as resilience. Endogenous mechanisms underlying neuronal invulnerability to chronic stress versus major depression are largely unknown. As GABAergic neurons are vulnerable to chronic stress and their impairments is associated with major depression, we have examined whether the invulnerability of GABAergic neurons in the limbic system is involved in resilience.

Results: GABAergic neurons in the nucleus accumbens from depression-like mice induced by chronic unpredictable mild stress appear the decreases in their GABA release, spiking capability and excitatory input reception, compared with those in resilience mice. The levels of decarboxylase and vesicular GABA transporters decrease in depression-like mice, but not resilience.

Materials and Methods: Mice were treated by chronic unpredictable mild stress for three weeks. Depression-like behaviors or resilience was confirmed by seeing whether their behaviors change significantly in sucrose preference, Y-maze and forced swimming tests. Mice from controls as well as depression and resilience in response to chronic unpredictable mild stress were studied in terms of GABAergic neuron activity in the nucleus accumbens by cell electrophysiology and protein chemistry.

Conclusions: The impairment of GABAergic neurons in the nucleus accumbens is associated with major depression. The invulnerability of GABAergic neurons to chronic stress may be one of cellular mechanisms for the resilience to chronic stress.


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