Reference - Detail
| RRC ID | 37603 |
|---|---|
| Author | Ichikawa T, Nakahata S, Tamura T, Manachai N, Morishita K. |
| Title | The loss of NDRG2 expression improves depressive behavior through increased phosphorylation of GSK3β. |
| Journal | Cell Signal |
| Abstract |
N-myc downstream-regulated gene 2 (NDRG2) is one of the important stress-inducible genes and plays a critical role in negatively regulating PI3K/AKT signaling during hypoxia and inflammation. Through recruitment of PP2A phosphatase, NDRG2 maintains the dephosphorylated status of PTEN to suppress excessive PI3K/AKT signaling, and loss of NDRG2 expression is frequently seen in various types of cancer with enhanced activation of PI3K/AKT signaling. Because NDRG2 is highly expressed in the nervous system, we investigated whether NDRG2 plays a functional role in the nervous system using Ndrg2-deficient mice. Ndrg2-deficient mice do not display any gross abnormalities in the nervous system, but they have a diminished behavioral response associated with anxiety. Ndrg2-deficient mice exhibited decreased immobility and increased head-dipping and rearing behavior in two behavioral models, indicating an improvement of emotional anxiety-like behavior. Moreover, treatment of wild-type mice with the antidepressant drug imipramine reduced the expression of Ndrg2 in the frontal cortex, which was due to the degradation of HIF-1α through reduced expression of HSP90 protein. Furthermore, we found that the down-regulation of Ndrg2 in Ndrg2-deficient mice and imipramine treatment improved mood behavior with enhanced phosphorylation of GSK3β through activation of PI3K/AKT signaling, suggesting that the expression level of NDRG2 has a causal influence on mood-related phenotypes. Collectively, these results suggest that NDRG2 may be a potential target for mood disorders such as depression and anxiety. |
| Volume | 27(10) |
| Pages | 2087-98 |
| Published | 2015-10-1 |
| DOI | 10.1016/j.cellsig.2015.07.012 |
| PII | S0898-6568(15)00209-0 |
| PMID | 26208882 |
| MeSH | Adaptor Proteins, Signal Transducing Affect Animals Antidepressive Agents, Tricyclic / pharmacology Cell Hypoxia Cell Line, Tumor Depression / metabolism* Depression / psychology Down-Regulation / drug effects Female Gene Expression Glycogen Synthase Kinase 3 / metabolism* Glycogen Synthase Kinase 3 beta HEK293 Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Imipramine / pharmacology Male Mice, Knockout Phosphorylation Protein Processing, Post-Translational Proteins / genetics* Proteins / metabolism Signal Transduction |
| IF | 3.968 |
| Times Cited | 8 |
| WOS Category | CELL BIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |