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

• Published in: Journal of integrative neuroscience 2018-01, Vol.17 (2), p.125-132
• Main Authors: Ni, Xinqiang, Liao, Yingzhao, Li, Limin, Zhang, Xiaoli, Wu, Zhengzhi
• Format: Article
• Language: English
• Subjects: Animals; Chronic Disease; Depressive Disorder - metabolism; Disease Models, Animal; Feeding Behavior - physiology; Glycogen Synthase Kinase 3 beta - metabolism; Hippocampus - metabolism; long non-coding rna|long non-coding rna tcons_00019174|depression|chronic stress mouse model|gsk3$\beta$|$\beta$-catenin pathway; Male; Mice, Inbred BALB C; Motor Activity - physiology; Neurons - metabolism; Random Allocation; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Social Behavior; Stress, Psychological - metabolism; Wnt Signaling Pathway - physiology
• ISSN: 0219-6352; 1757-448X; 1757-448X
• DOI: 10.31083/JIN-170052

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 over expression in hippocampal neurons improved the behaviors of mice exposed to chronic ultra-mild stress. Further, it was found long non-coding RNA TCONS_00019174 over expression upregulated phosphorylated-GSK3β (p-GSK3β) protein and β-catenin in the hippocampus. These findings suggest that long non-coding RNA TCONS_00019174 exerts antidepressant-like effect in mice by activating a Wnt/β-catenin pathway, and that long non-coding RNA may serve as a potential therapeutic target for major depressive disorder in clinical application.