Transcriptional regulation of neurogenesis: potential mechanisms in cerebral ischemia

Abstract

Recent data provides evidence that new neurons are born in cerebral ischemia. Although ultimate evidence for their functional importance is lacking, correlational data suggest that they contribute to recovery. Therefore, the underlying mechanisms of neurogenesis are interesting as a basis for pharmacological enhancement of the phenomenon. Neurogenesis is a multistep process that includes proliferation of precursor cells, migration of the newborn cells to the site of lesion, differentiation, integration into neuronal circuits, and survival. All these steps rely on gene transcription. However, only preliminary data about the specific transcriptional control of neurogenesis in cerebral ischemia have been obtained so far. To promote this investigation, we review currently available information on six pathways (Notch, Wnt/beta-catenin, NF-kappaB, signal transducers and activators of transcription (STA) 3, HIF-1, and cyclic AMP response element-binding protein [CREB]) that have been shown to regulate transcription in neurogenesis and that have been implicated in cerebral ischemia. With the exception of CREB, direct involvement in postischemic neurogenesis is quite conjectural and much more must be learned to draw practical conclusions.