Clusterin increases post-ischemic damages in organotypic hippocampal slice cultures

Détails

ID Serval
serval:BIB_017BB890425C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Clusterin increases post-ischemic damages in organotypic hippocampal slice cultures
Périodique
Journal of neurochemistry
Auteur(s)
Hakkoum David, Imhof Anouk, Vallet Philippe G., Boze Hélène, Moulin Guy, Charnay Yves, Stoppini Luc, Aronow Bruce, Bouras Constantin, Giannakopoulos Panteleimon
ISSN
0022-3042
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
106
Numéro
4
Pages
1791-1803
Langue
anglais
Notes
SAPHIRID:70503
Résumé
Clusterin or apolipoprotein J is a heterodimeric glycoprotein which is known to be increased during tissue involution in response to hormonal changes or injury and under circumstances leading to apoptosis. Previous studies in wild-type (WT) and clusterin-null (Clu-/-) mice indicated a protective role of clusterin over-expression in astrocytes lasting up to 90 days post-ischemia. However, in in vitro and in vivo models of neonatal hypoxia-ischemia, clusterin exacerbates necrotic cell death. We developed recombinant forms of clusterin and examined their effect on propidium iodide uptake, neuronal and synaptic markers as well as electrophysiological recordings in hippocampal slice cultures from Clu-/- and WT mice subjected to oxygen-glucose deprivation (OGD). WT mice displayed a marked up-regulation of clusterin associated with electrophysiological deficits and dramatic increase of propidium iodide uptake 5 days post-OGD. Immunocytochemical and western blot analyses revealed a substantial decrease of neuronal nuclei and synaptophysin immunoreactivity that predominated in WT mice. These findings contrasted with the relative post-OGD resistance of Clu-/- mice. The addition of biologically active recombinant forms of human clusterin for 24 h post-OGD led to the abolishment of the ischemic tolerance in Clu-/- slices. This deleterious effect of clusterin was reverted by the concomitant administration of the NMDA receptor antagonist, d-2-amino-5-phosphonopentanoate. The present data indicate that in an in vitro model of ischemia characterized by the predominance of NMDA-mediated cell death, clusterin exerts a negative effect on the structural integrity and functionality of hippocampal neurons.
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/11/2008 12:23
Dernière modification de la notice
20/08/2019 13:23
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