title: Differential cell proliferation in the cortex of the APPswePS1dE9 Alzheimer's disease mouse model.
abstract: 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.
authors.affiliation: Netherlands Institute for Neuroscience-an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Department of Astrocyte Biology and Neurodegeneration, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands. w.kamphuis@nin.knaw.nl
authors.forename: Willem
authors.initials: W
authors.lastname: Kamphuis
authors.forename: Marie
authors.initials: M
authors.lastname: Orre
authors.forename: Lieneke
authors.initials: L
authors.lastname: Kooijman
authors.forename: Maurice
authors.initials: M
authors.lastname: Dahmen
authors.forename: Elly M
authors.initials: EM
authors.lastname: Hol
mesh_terms: D000367:Age Factors; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000473:pathology*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000235:genetics*; D005911:Gliosis / Q000209:etiology; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D053764:Presenilin-1 / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics
chemical_list: D016564:Amyloid beta-Protein Precursor; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D017252:CD3 Complex; D002135:Calcium-Binding Proteins; D019394:Ki-67 Antigen; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D053764:Presenilin-1; D055748:SOXB1 Transcription Factors; C491049:Aif1 protein, mouse; C512773:Olig2 protein, mouse; C508853:PSEN1 protein, human; C527783:Sox2 protein, mouse