title: 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 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.
authors.affiliation: INSERM, U840, Collège de France, 11 Place Marcelin Berthelot, 75005 Paris, France.
authors.forename: X
authors.initials: X
authors.lastname: Mei
authors.forename: P
authors.initials: P
authors.lastname: Ezan
authors.forename: C
authors.initials: C
authors.lastname: Giaume
authors.forename: A
authors.initials: A
authors.lastname: Koulakoff
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology*; D017630:Connexins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000473:pathology*; D053764:Presenilin-1 / Q000235:genetics*; D013223:Statistics as Topic
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D017630:Connexins; C508853:PSEN1 protein, human; D053764:Presenilin-1