Activation of cAMP-response-element-binding protein (CREB) after focal cerebral ischemia stimulates neurogenesis in the adult dentate gyrus.
New neurons are generated in adult mammalians and may contribute to repairing the brain after injury. Here, we show that the number of new neurons in the dentate gyrus of adult rats increased in cerebral ischemic stroke and correlated with activation of the cAMP-response-element-binding protein (CREB). Inhibition of endogenous CREB by expression of a dominant-negative mutant of CREB (CREB-S133A or CREB-R287L) blocked ischemia-induced neurogenesis in the dentate gyrus of adult rats, whereas expression of constitutively active CREB, VP16-CREB, increased the number of new neurons. Thus, our findings provide roles and regulatory mechanisms for CREB in adult neurogenesis and possibly suggest a practical strategy for replacing dead neurons in brain injury.
Zhu
Dong Ya
DY
Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, AB, Canada T2N 4N1.
Lau
Lorraine
L
Liu
Shu Hong
SH
Wei
Jian She
JS
Lu
You Ming
YM
D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics* / Q000378:metabolism*; D018891:Dentate Gyrus / Q000503:physiopathology*; D005260:Female; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D016296:Mutagenesis; D016297:Mutagenesis, Site-Directed; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012727:Sex Characteristics
D017362:Cyclic AMP Response Element-Binding Protein; D011994:Recombinant Proteins