REDD1 is essential for stress-induced synaptic loss and depressive behavior (Nature Medicine 2014, 20, 531–535)

報告日期: 2015/05/15
報告時間: 15:10/16:00
報告學生: 徐詩涵(以英文報告)
講評老師: 黃阿敏
附件下載: 下載[1490-1425859367-1.pdf] 

REDD1 is essential for stress-induced synaptic loss and depressive behavior

Kristie T Ota, et al.

Nature Medicine 2014; vol.20: 531–535

Student: Shih-Han Hsu (徐詩涵)

Time: 15:10-16:00, May.15, 2015

Commentator: A-Min Huang (黃阿敏), Ph.D.

Place: Room 602


Chronic unpredictable stress (CUS) is implicated to neuronal atrophy in the prefrontal cortex (PFC) of human subjects with major depressive disorder (MDD), but the underlying mechanism has remained unknown. Postmortem findings showed increased REDD1 (regulated in development and DNA damage responses-1, which is an mTORc1 inhibitor) expression in the PFC of MDD patients. The authors also found increased REDD1 levels and decreased phosphorylation of mTORc1 signaling proteins in rat PFC under CUS treatment. The authors investigated the role of REDD1 in CUS-induced neuronal alteration by using mouse and rat models. Mutant mice with REDD1 deletion are resilient to the synaptic, behavioral and mTORC1 signaling deficits caused by CUS. The spine density and the frequency of serotonin (5-HT)- and hypocretin (Hcrt)-induced EPSCs from REDD1-KO mice under CUS is similar to unstressed REDD1-KO mice. On the other hand, rats with viral-mediated overexpression of REDD1 showed anxiety- and depressive-like behaviors, including lower sucrose preference, increased immobility, longer latency to feed, lower center frequency in the open field and less arm entries in the elevated plus maze. Neuronal atrophy was observed in the PFC of REDD1-OE rats by using enhanced spine platform (ESP) to perform dendritic spine analysis. Taken together, the authors identified REDD1 as an important messenger that transfers CUS into neuron cells and may be a potential pharmacological target for treatments of patients with MDD.


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