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LncRNA Gm16638-201 Inhibits the 14-3-3Ɛ Pathway in the Murine Prefrontal Cortex to Induce Depressive Behaviors.
- Source :
-
Biological & pharmaceutical bulletin [Biol Pharm Bull] 2022; Vol. 45 (11), pp. 1616-1626. - Publication Year :
- 2022
-
Abstract
- The dysregulation of certain long non-coding RNAs (lncRNAs) has been considered to be involved in neuropsychiatric disorders such as depression, implying the vital role of these transcripts. We have previously identified many differentially expressed lncRNAs in chronic unpredictable mild stress (CUMS) induced mice. Among them, lncRNA Gm16638-201 was highly expressed in the hippocampus (HIP) of CUMS, but the specific role and the underlying mechanisms remain unclear. Here, we reported that lncRNA Gm16638-201 was highly expressed in the prefrontal cortex (PFC) of CUMS induced depressive mice. Bioinformatic analysis shows that Gm16638-201 is mainly located in the cytoplasm. Nine neurological-related genes (Elmo2, Satb1, Hnrnpul1, Sipa1l3, Mapt, Tada3, Sgip1, IL-16, and StarD5) were predicted to be regulated in cis or trans by Gm16638-201 and involved into the 14-3-3Ɛ neurotrophic signaling pathway. We further confirmed the down-regulation of 14-3-3Ɛ and the nine predicted target genes in the PFC of CUMS mice except for Sgip1 and IL-16. In addition, they were also down-regulated in the primary cortical cell cultures with overexpression of Gm16638-201 constructed using an adenoviral-medicated gene expression system. In conclusion, we found that overexpression of Gm16638-201 negatively regulated several target genes and inhibited the 14-3-3Ɛ pathway in the PFC of CUMS induced depressive mice. This promising result suggests that Gm16638-201 may be a potential novel therapeutic target for depression.
- Subjects :
- Mice
Animals
Depression drug therapy
Stress, Psychological metabolism
Interleukin-16 metabolism
Disease Models, Animal
Prefrontal Cortex metabolism
Hippocampus metabolism
Cytoskeletal Proteins metabolism
Adaptor Proteins, Signal Transducing genetics
Adaptor Proteins, Signal Transducing metabolism
Transcription Factors metabolism
Antidepressive Agents therapeutic use
RNA, Long Noncoding genetics
RNA, Long Noncoding metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1347-5215
- Volume :
- 45
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Biological & pharmaceutical bulletin
- Publication Type :
- Academic Journal
- Accession number :
- 36328497
- Full Text :
- https://doi.org/10.1248/bpb.b22-00184