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O3‐04‐04: BMP4/NOGGIN contribute to abnormal neurogenesis in the adult hippocampal of APPSWE/PS1 e9 transgenic mouse model of Alzheimer's disease
Author(s) -
Tang Jun
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.1411
Subject(s) - noggin , neurogenesis , hippocampal formation , endocrinology , medicine , hippocampus , genetically modified mouse , biology , chemistry , bone morphogenetic protein , neuroscience , microbiology and biotechnology , transgene , biochemistry , gene
Background: DG area of hippocampus in the brain is where neurogenesisprocess continues into adulthood. Perturbation of neurogenesis can alterhippocampal function. Bone morphogenetic protein-4 and its antagonist Noggin arecrucial to both embryonic development and the adult nervous system. However, itis not known whether BMP4 /Noggin could contribute to the regulation ofabnormal neurogenesis in APPswe/PS1DeltaE9 dtg mouse models.Methods: BrdU labeled is used forthe analysis of adult hippocampal neurogenesis. Pathological and behavioral test were also applied. In situ hybridization and immonuhistochemistry are usedfor the expression of BMP4/Noggin in hippocampus at mRNA and protein levels, and the Noggin/Fc chimera were injected into lateral ventricle to investigate the fuction of Noggin in the proliferation and differentiation of NSCs in hippocampus. Results: 1) BrdU-labelled cells in DG of 9and12-month-old dtg (+/+) mice was markedly reduced compared with age-matched dtg(-/-)littermates. There exist significant negative correlation between the BrdUcells and Abeta plaques in the brain. 2) higher expression of BMP4 and lower expression of Noggin are proved to be age dependent, and negatively correlated with each other. 3) decreased neurogenesis in AD dtg mice was significantly correlation with the increased expression of BMP4 and decreased expression ofNoggin at both mRNA and protein levels; 4) Intraventricular administration of a chimeric Noggin/Fc protein resulted in a significant increase in the number ofBrdU-labeled cells and the NSC-derived differentiated cells in APP/PS1 mice. Conclusions: BMP4 and Noggin couldco-modulate and contribute to the abnormal adult neurogenesis process inhippocampus of APPswe/PS1DE9 dtg mice models.