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The increased density of p38 mitogen‐activated protein kinase‐immunoreactive microglia in the sensorimotor cortex of aged TgCRND8 mice is associated predominantly with smaller dense‐core amyloid plaques
Author(s) -
ChlanFourney J.,
Zhao T.,
Walz W.,
Mousseau D. D.
Publication year - 2011
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2010.07597.x
Subject(s) - microglia , senile plaques , p38 mitogen activated protein kinases , protein kinase a , mapk/erk pathway , cortex (anatomy) , biology , pathology , neuroscience , chemistry , alzheimer's disease , kinase , microbiology and biotechnology , medicine , immunology , inflammation , disease
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.