Cocaine regulates MEF2 to control synaptic and behavioral plasticity (Neuron, 2008, 59:621-633)

報告日期: 2008/12/12
報告時間: 16:00/16:50
報告學生: 陳建仲
講評老師: 簡伯武
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/971212-2.pdf

Cocaine Regulates MEF2 to Control Synaptic and Behavioral Plasticity

Neuron 59621–633, 2008.

 

Speaker : Chien-Chung Chen( 陳建仲 )

Commentator : Po-Wu Gean, Ph. D. ( 簡伯武 老師 )

Time : 16:00 ~ 17:00 December 12, 2008

Place : Room 602

 

Abstract

Drug addiction is a state in which the body relies on a substance for normal function and develops physical dependence. A major clinical challenge for effective treatment of drug addiction is its persistence even after long periods of drug abstinence. Long term exposure to cocaine makes an increase in dendritic spine density in the nucleus accumben (NAc). Structural changes have shown to be associated with the development of addictive behavior. Cdk5 phosphorylates MEF2 which binds to DNA as hetero- and homodimers to regulate cardiac and skeletal muscle development. It has been shown that facilitate Cdk5 may increase in dendritic spine density. How does MEF2 work in the nerve system have remained unknown. MEF2 signaling pathway is involved in cocaine-mediated regulation of NAc spine density by increasing MEF2 phosphorylation to suppress its activity. Therefore, increase MEF2 activity to block spine plasticity might prevent drug addictive behavior. However MEF2 expression unexpectedly leads to stronger cocaine-induced locomotor sensitization. In conclusion, cocaine-induced increase in spine density is not required for locomotor sensitization and reward learning; however it may instead represent a compensatory process to limit behavior changes.

 

References

Hyman, S.E., Malenka, R.C. and Nestler, E.J. (2006). Neural mechanisms of addiction: the role of reward-related learning and memory, Annu. Rev. Neurosci. 29:565–598.

Lee K.W., Kim Y., Kim A.M., Helmin K., Nairn A.C. and Greengard P. (2006). Cocaine- induced dendritic spine formation in D1 and D2 dopamine receptor- containing medium spiny neurons in nucleus accumbens. Proc. Natl. Acad. Sci. 103:3399 – 3404