A negative regulator of MAP kinase causes depressive behavior (Nat Med, 2010, 16:1328-1332)

報告日期: 2011/05/06
報告時間: 15:10/16:00
報告學生: 陳麗仙 (英文報告)
講評老師: 郭余民
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Full Text: http://basicmed.med.ncku.edu.tw/admin/up_img/0506-1.pdf

A Negative Regulator of MAP Kinase Causes Depressive Behavior
Nature Medicine 2010 16:1328-1333.
Duric V, Banasr M, Licznerski P, Schmidt HD, Stockmeier CA, Simen AA, Newton SS, Duman RS.
 
Commentator: Yu-Min Kuo, Ph.D (郭余民  老師)
Speaker: Li-hsien Chen (陳麗仙)
Date: 05/06 15:10 – 16:00
Place: Room 602
Abstract:
Depression ruins the millions of people’s lives, causing suffering and distress. The major depressive disorder (MDD) is associated with functional and structural alterations of hippocampus which are thought to underlie primary symptoms of the disease, including impaired cognition and depressed mood1,2. However, the molecular changes that cause the pathophysiology of MDD are still unknown. Thus, these authors use a whole genome expression analysis of postmortem tissue and find increased mitogen activated protein kinase phosphatase-1 (MKP-1) expression in the hippcampal subregions (CA1 and dente gyrus) in indiviudals afflicited with MDD. MKP-1 is a tyrosine and theronine phaspatase that regulates the activity of neurotrophic factor-MAPK cascades, which is a major signaling pathway involved in neuronal plasticity, proliferation and survival3.
To further examine the potential role and function of MKP-1 overexpression in MDD, the authors use the chronic unpredictable stress (CUS) model to induce animal depressive-like behaviors. The MKP-1 overexpression and depressive behaviors induced by CUS are reversed by chronic antidepressant administration. Subsequently, they attempt both viral vector and knockout approaches to determine the influence of increased expression or deletion of MKP-1 on depressive behavior in rat and mouse models, respectively. Rats transfected with MKP-1 in the dente gyrus and CA1 show depressive behavioral responses in helplessness and anhedonia paradigms. In parallel with these findings, mice without MKP-1 expression protect them from exhibiting depressive behaviors after CUS. Taken together, these authors suggest that MKP-1 is a key control regulator in the pathophysiology of MDD and MKP-1 may be a new target for developing efficacious antidepressant.
References:
1.     Stockmeier, C.A. et al. Cellular changes in the postmortem hippocampus in majordepression.Biol. Psychiatry 56, 640–650 (2004).
2.     Swaab, D.F., Bao, A.M. & Lucassen, P.J. The stress system in the human brain in depression and neurodegeneration. Ageing Res. Rev. 4, 141–194 (2005).
3.     Duman, C.H., Schlesinger, L., Kodama, M., Russell, D.S. & Duman, R.S. A role for MAP kinase signaling in behavioral models of depression and antidepressanttreatment.Biol. Psychiatry 61, 661–670 (2007).