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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.

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 amyloidprotein 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.
AuthorsJ Chlan-Fourney, T Zhao, W Walz, D D Mousseau
JournalThe European journal of neuroscience (Eur J Neurosci) Vol. 33 Issue 8 Pg. 1433-44 (Apr 2011) ISSN: 1460-9568 [Electronic] France
PMID21323766 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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
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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