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Open Access Highly Accessed Research article

Period 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus

Laurence Borgs1, Pierre Beukelaers1, Renaud Vandenbosch1, Laurent Nguyen1, Gustave Moonen12, Pierre Maquet23, Urs Albrecht4, Shibeshih Belachew12 and Brigitte Malgrange1*

Author Affiliations

1 Developmental Neurobiology Unit, Center for Cellular and Molecular Neurobiology, University of Liège, C.H.U. B36, 4000 Liège, Belgium

2 Department of Neurology, C.H.U. Sart Tilman, B35, 4000 Liège, Belgium

3 Cyclotron Research Center, University of Liège, B30, 4000 Liège, Belgium

4 Department of Medicine, Division of Biochemistry, University of Fribourg, Friboug, Switzerland

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BMC Neuroscience 2009, 10:30  doi:10.1186/1471-2202-10-30

Published: 27 March 2009

Abstract

Background

Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG.

Results

In contrast to the suprachiasmatic nucleus, we observed a non-rhythmic constitutive expression of mPER2 in the dentate gyrus. We provide evidence that mPER2 is expressed in proliferating neural stem/progenitor cells (NPCs) and persists in early post-mitotic and mature newborn neurons from the adult DG. In vitro and in vivo analysis of a mouse line mutant in the mPer2 gene (Per2Brdm1), revealed a higher density of dividing NPCs together with an increased number of immature newborn neurons populating the DG. However, we showed that the lack of mPer2 does not change the total amount of mature adult-generated hippocampal neurons, because of a compensatory increase in neuronal cell death.

Conclusion

Taken together, these data demonstrated a functional link between the constitutive expression of mPER2 and the intrinsic control of neural stem/progenitor cells proliferation, cell death and neurogenesis in the dentate gyrus of adult mice.