Journal
NEUROCHEMISTRY INTERNATIONAL
Volume 54, Issue 5-6, Pages 277-285Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2008.12.005
Keywords
Circadian rhythm; Clock; Bmal1; Adult neural stem/progenitor cell; Adult neurogenesis; NeuroD1
Categories
Funding
- Ministry of Health, Labour and Welfare of Japan
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation
- Japan Science and Technology Agency
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The circadian clock system plays multiple roles in our bodies, and clock genes are expressed in various brain regions, including the lateral subventricular zone (SVZ) where neural stem/progenitor cells (NSPCs) persist and postnatal neurogenesis continues. However, the functions of clock genes in adult NSPCs are not well understood. Here, we first investigated the expression patterns of Clock and Bmal1 in the SVZ by immunohistochemistry and then verified how the expression levels of 17 clock and clock-related genes changed during differentiation of cultured adult NSPCs using quantitative RT-PCR. Finally, we used RNAi to observe the effects of Clock and Bmal1 on neuronal differentiation. Our results revealed that Clock and Bmal1 were expressed in the SVZ and double-stained with the neural progenitor marker Nestin and neural stem marker GFAP. In cultured adult NSPCs, the clock genes changed their expression patterns during differentiation, and interestingly, Bmal1 started endogenous oscillation. Moreover, gene silencing of Clock or Bmal1 by RNAi decreased the percentages of neuronal marker Map2-positive cells and expression levels of NeuroD1 mRNA. These findings suggest that clock genes are involved in the neuronal differentiation of adult NSPCs and may extend our understanding of various neurological/psychological disorders linked to adult neurogenesis and circadian rhythm. (C) 2008 Elsevier Ltd. All rights reserved.
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