IMR Press / JIN / Volume 17 / Issue 2 / DOI: 10.31083/JIN-170052
Open Access Research article
Therapeutic role of long non-coding RNA TCONS_00019174 in depressive disorders is dependent on Wnt/β-catenin signaling pathway
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1 Shenzhen Institute of Traditional Chinese and Western Medicine, Shenzhen Second People's Hospital, Shenzhen, Guangdong, P.R. China
2 Pediatrics of Chinese Medicine, Shenzhen Hospital of Chinese Medicine, Shenzhen, Guangdong, P.R. China
3 Shenzhen Institute of Geriatrics, Shenzhen, Guangdong, 518037, P.R. China
*Correspondence: (Zhengzhi Wu)
J. Integr. Neurosci. 2018, 17(2), 125–132;
Submitted: 21 August 2017 | Accepted: 8 September 2017 | Published: 15 May 2018

Chronic stress is one of the major causes that lead to major depressive disorder, which is a prevalent mood disorder worldwide. Many patients with major depressive disorder do not benefit from available medication due to the complex etiology of the condition. Recently, long non-coding RNAs, molecular switches of downstream genes expression, have been reported to be involved in the pathogenesis of major depressive disorder. The long non-coding RNA TCONS_00019174 has been implicated in major depressive disorder risk and antidepressant effects, However, the effect of long non-coding RNA TCONS_00019174 on antidepressant responses has not been investigated. This study is designed to determine whether altered expression of long non-coding RNA TCONS_00019174 contributes to depression-like behaviors associated with chronic stress. We found that mice exposed to chronic ultra-mild stress displayed apparent depression-like behaviors and decreased expression of long non-coding RNA TCONS_00019174 in hippocampus. Both changed behaviors and long non-coding RNA TCONS_00019174 expression level were rescued by chronic treatment with imipramine. Viral-mediated long non-coding RNA TCONS_00019174 overexpression in hippocampal neurons improved the behaviors of mice exposed to chronic ultra-mild stress. Further, it was found long non-coding RNA TCONS_00019174 overexpression upregulated phosphorylated-GSK3$\beta$(p-GSK3$\beta$) protein and $\beta$-catenin in the hippocampus. These findings suggest that long non-coding RNA TCONS_00019174 exerts antidepressant-like effect in mice by activating a Wnt/$\beta$-catenin pathway, and that long non-coding RNA may serve as a potential therapeutic target for major depressive disorder in clinical application.

long non-coding RNA
long non-coding RNA TCONS_00019174
chronic stress mouse model
$\beta$-catenin pathway
Fig. 1.
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