Astroglial connexin immunoreactivity is specifically altered at β-amyloid plaques in β-amyloid precursor protein/presenilin1 mice

Abstract Activation of astrocytes surrounding amyloid plaques is a hallmark of Alzheimer disease (AD) with consequences yet poorly understood. Astrocytes are characterized by a high level of intercellular communication mediated by two gap-junction forming proteins, connexin-43 and connexin-30. As as...

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Bibliographic Details
Published in:Neuroscience 2010-11, Vol.171 (1), p.92-105
Main Authors: Mei, X, Ezan, P, Giaume, C, Koulakoff, A
Format: Article
Language:English
Subjects:
Age Factors
Alzheimer
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - genetics
Animals
Astrocytes - metabolism
Biological and medical sciences
Brain - cytology
Connexins - metabolism
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Fundamental and applied biological sciences. Psychology
gap junction forming proteins
Gene Expression Regulation - genetics
Humans
Medical sciences
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurology
Plaque, Amyloid - pathology
Presenilin-1 - genetics
reactive astrocytes
Statistics as Topic
Vertebrates: nervous system and sense organs
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Summary:Abstract Activation of astrocytes surrounding amyloid plaques is a hallmark of Alzheimer disease (AD) with consequences yet poorly understood. Astrocytes are characterized by a high level of intercellular communication mediated by two gap-junction forming proteins, connexin-43 and connexin-30. As astroglial connexins (Cxs) are involved in neuronal dysfunctions and death, we have analyzed their expression pattern in two murine models of AD, that is two different β-amyloid precursor protein (APP)/presenilin1(PS1) mice, using western blot and immunohistochemistry analyzed in confocal microscopy. In young mice at 2 months, before the emergence of β-amyloid (Aβ) deposits, the distribution of both Cxs was similar to that of control mice. In older animals≥4 months, local modifications in connexin immunostaining pattern were observed in the microenvironment of dense core Aβ plaques. In a majority of plaques, an elevated immunoreactivity was detected for both Cxs contributing to the overall increase in connexin expression detected in 18 month old APP/PS1 mice. Activated microglial cells did not contribute to the elevated connexin immunoreactivity that was concentrated in astroglial processes infiltrating the plaques. In a small proportion of plaques (≤15%) a depletion of immunoreactive connexin puncta was also found. As astroglial Cxs participate in neuroglial interactions, their remodeling may contribute to neuronal alterations observed at the periplaque area.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2010.08.001