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Differential cell proliferation in the cortex of the appsweps1de9 alzheimer's disease mouse model
Author(s) -
Kamphuis Willem,
Orre Marie,
Kooijman Lieneke,
Dahmen Maurice,
Hol Elly M.
Publication year - 2012
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22295
Subject(s) - microglia , biology , neurogenesis , subventricular zone , astrocyte , microbiology and biotechnology , cell growth , proliferation marker , pathology , immunology , stem cell , neuroscience , neural stem cell , inflammation , immunohistochemistry , central nervous system , medicine , genetics
Plaque deposition in Alzheimer's disease (AD) is known to decrease proliferation in neurogenic niches in AD mouse models, but the effects on cell proliferation and differentiation in other brain areas have not been studied in detail. We analyzed cell proliferation in the cortex of wild type (WT) and APPswePS1dE9 transgenic (AD) mice at different ages. Mice were studied shortly after the last BrdU injection (BrdU[ST]). In AD mice, the number of proliferating cells increased fourfold, coinciding with plaque appearance and its associated reactive gliosis and activation of microglia. An increase in the number of BrdU[ST]‐cells expressing markers for activated microglia is underlying the enhanced proliferation. Cortical reactive astrocytes did not become proliferative since BrdU[ST]‐cells were negative for different astrocyte‐specific markers. The number of Olig2‐positive oligodendrocyte precursor cells was unchanged. Four weeks after the last BrdU application, the number of BrdU[LT]‐cells with an activated microglia signature was still enhanced in AD mice. None of the newborn cells had differentiated into oligodendrocytes, astrocytes, or neurons. On the basis of these observations, we conclude that amyloid plaque deposition increases proliferation of microglia around plaques but does not affect the proliferation of cortical oligodendrocyte precursor cells. No evidence was found for damage‐induced proliferation of reactive astrocytes or for a redirected neurogenesis from the subventricular zone. The proliferation of microglia contributes to the rapid accumulation of microglia around plaques and may play a role in limitating plaque expansion. © 2012 Wiley Periodicals, Inc.