Tags

Type your tag names separated by a space and hit enter

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    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

    , , ,

    Source

    Glia 60:4 2012 Apr pg 615-29

    MeSH

    Age Factors
    Alzheimer Disease
    Amyloid beta-Protein Precursor
    Animals
    Basic Helix-Loop-Helix Transcription Factors
    Bromodeoxyuridine
    CD3 Complex
    Calcium-Binding Proteins
    Cell Differentiation
    Cell Proliferation
    Cerebral Cortex
    Disease Models, Animal
    Gene Expression Regulation
    Gliosis
    Humans
    Ki-67 Antigen
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Microfilament Proteins
    Nerve Tissue Proteins
    Neuroglia
    Neurons
    Oligodendrocyte Transcription Factor 2
    Presenilin-1
    SOXB1 Transcription Factors
    Sequence Deletion

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22262260

    Citation

    Kamphuis, Willem, et al. "Differential Cell Proliferation in the Cortex of the APPswePS1dE9 Alzheimer's Disease Mouse Model." Glia, vol. 60, no. 4, 2012, pp. 615-29.
    Kamphuis W, Orre M, Kooijman L, et al. Differential cell proliferation in the cortex of the APPswePS1dE9 Alzheimer's disease mouse model. Glia. 2012;60(4):615-29.
    Kamphuis, W., Orre, M., Kooijman, L., Dahmen, M., & Hol, E. M. (2012). Differential cell proliferation in the cortex of the APPswePS1dE9 Alzheimer's disease mouse model. Glia, 60(4), pp. 615-29. doi:10.1002/glia.22295.
    Kamphuis W, et al. Differential Cell Proliferation in the Cortex of the APPswePS1dE9 Alzheimer's Disease Mouse Model. Glia. 2012;60(4):615-29. PubMed PMID: 22262260.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Differential cell proliferation in the cortex of the APPswePS1dE9 Alzheimer's disease mouse model. AU - Kamphuis,Willem, AU - Orre,Marie, AU - Kooijman,Lieneke, AU - Dahmen,Maurice, AU - Hol,Elly M, Y1 - 2012/01/19/ PY - 2011/09/25/received PY - 2011/12/21/accepted PY - 2012/1/21/entrez PY - 2012/1/21/pubmed PY - 2012/6/13/medline SP - 615 EP - 29 JF - Glia JO - Glia VL - 60 IS - 4 N2 - 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. SN - 1098-1136 UR - https://www.unboundmedicine.com/medline/citation/22262260/Differential_cell_proliferation_in_the_cortex_of_the_APPswePS1dE9_Alzheimer's_disease_mouse_model_ L2 - https://doi.org/10.1002/glia.22295 DB - PRIME DP - Unbound Medicine ER -