کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10814834 | 1058411 | 2015 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The loss of NDRG2 expression improves depressive behavior through increased phosphorylation of GSK3β
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Signalling - Volume 27, Issue 10, October 2015, Pages 2087-2098
Journal: Cellular Signalling - Volume 27, Issue 10, October 2015, Pages 2087-2098
نویسندگان
Tomonaga Ichikawa, Shingo Nakahata, Tomohiro Tamura, Nawin Manachai, Kazuhiro Morishita,