Dabing Li and Jun Tang contributed equally to this work.
Decreased hippocampal cell proliferation correlates with increased expression of BMP4 in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease
Version of Record online: 8 APR 2008
Copyright © 2008 Wiley-Liss, Inc.
Volume 18, Issue 7, pages 692–698, July 2008
How to Cite
Li, D., Tang, J., Xu, H., Fan, X., Bai, Y. and Yang, L. (2008), Decreased hippocampal cell proliferation correlates with increased expression of BMP4 in the APPswe/PS1ΔE9 mouse model of Alzheimer's disease. Hippocampus, 18: 692–698. doi: 10.1002/hipo.20428
- Issue online: 16 JUN 2008
- Version of Record online: 8 APR 2008
- Manuscript Accepted: 30 JAN 2008
- National Natural Science Foundation of China. Grant Numbers: 30500148, 30571770
- Alzheimer's disease;
Alterations in hippocampal cell proliferation have been identified in transgenic (tg) mouse models of Alzheimer's disease (AD); however, relatively little is known about the underlying mechanisms. Previously, we have demonstrated that endogenous level of BMP4 in the dentate gyrus (DG) affects hippocampal cell proliferation in a pentylentetrazol kindling-induced epilepsy model. In the present study, we evaluated hippocampal cell proliferation and BMP4 mRNA level in the APPswe/PS1ΔE9 tg mouse, a well-established mouse model in which coexpression of familial AD-linked APP “Swedish” (APPswe) and PS1ΔE9 polypeptide variants leads to Aβ deposition throughout the hippocampus and cortex. The number of bromodeoxyuridine (BrdU)-labeled cells in the DG subgranular zone (DG-SGZ) of 9- and 12-month-old APPswe/PS1ΔE9 tg mice was markedly reduced compared with age-matched nontransgenic littermates, whereas, the BMP4 mRNA level was significantly increased in the tg mice. There was a significant correlation between the increased BMP4 mRNA expression and the decreased number of BrdU labeled cells. After effectively blocking the expression of endogenous BMP4 with antisense oligodeoxynucleotides (ASODN), the decrease in hippocampal cell proliferation in the DG-SGZ and hilus of 9- and 12-month-old tg mice was reversed. These findings suggest that the increased expression of BMP4 mRNA within the DG of the hippocampus may contribute to the decrease in cell proliferation in APPswe/PS1ΔE9 tg mice. © 2008 Wiley-Liss, Inc.