Abstract |
The role for phosphorylated p38 mitogen-activated protein kinase [p- p38(MAPK)] in β- amyloid plaque deposition [a hallmark of Alzheimer's disease (AD) pathology] remains ambiguous. We combined immunohistochemistry and stereological sampling to quantify the distribution of plaques and p-p38(MAPK)-immunoreactive (IR) cells in the sensorimotor cortex of 3-, 6- and 10-month-old TgCRND8 mice. The aggressive nature of the AD-related human amyloid-β protein precursor expressed in these mice was confirmed by the appearance of both dense-core ( thioflavin-S-positive) and diffuse plaques, even in the youngest mice. p-p38(MAPK)-IR cells of the sensorimotor cortex were predominantly co-immunoreactive for the Macrophage-1 (CD11b/CD18) microglial marker. These p-p38(MAPK)-IR microglia were associated with both dense-core and diffuse plaques, but the expected age-dependent increase in the density of plaque-associated p-p38(MAPK)-IR microglia was restricted to dense-core plaques. Furthermore, the density of dense-core plaque-associated p-p38(MAPK)-IR microglia was inversely correlated with the size of the core within the given plaque, which supports a role for these microglia in restricting core growth. p-p38(MAPK)-IR microglia were also observed throughout wildtype and TgCRND8 mouse cortical parenchyma, but the density of these non-plaque-associated microglia remained constant, regardless of age or genotype. We conclude that the constitutive presence of p-p38(MAPK)-IR microglia in aging mouse brain is indicative of a longitudinal role for this kinase in normal brain physiology. We suggest that this fact, as well as the fact that a pool of p-p38(MAPK)-IR microglia appears to restrict β- amyloid plaque core development, needs to be duly considered when ascribing functions for p38(MAPK) signalling in the AD brain.
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Authors | J Chlan-Fourney, T Zhao, W Walz, D D Mousseau |
Journal | The European journal of neuroscience
(Eur J Neurosci)
Vol. 33
Issue 8
Pg. 1433-44
(Apr 2011)
ISSN: 1460-9568 [Electronic] France |
PMID | 21323766
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd. |
Chemical References |
- Amyloid beta-Protein Precursor
- p38 Mitogen-Activated Protein Kinases
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Topics |
- Aging
(metabolism, pathology)
- Amyloid beta-Protein Precursor
(genetics, metabolism)
- Animals
- Cerebral Cortex
(cytology, pathology)
- Humans
- Immunohistochemistry
- Mice
- Mice, Transgenic
- Microglia
(cytology, metabolism)
- Neurons
(cytology, metabolism)
- Plaque, Amyloid
(metabolism, pathology)
- p38 Mitogen-Activated Protein Kinases
(metabolism)
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