Therapeutic role of long non-coding RNA TCONS_00019174 in depressive disorders is dependent on Wnt/β-catenin signaling pathway

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.