Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus

Citation
Dg. Xu et al., Attenuation of ischemia-induced cellular and behavioral deficits by X chromosome-linked inhibitor of apoptosis protein overexpression in the rat hippocampus, J NEUROSC, 19(12), 1999, pp. 5026-5033
Citations number
31
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
19
Issue
12
Year of publication
1999
Pages
5026 - 5033
Database
ISI
SICI code
0270-6474(19990615)19:12<5026:AOICAB>2.0.ZU;2-D
Abstract
Transient forebrain ischemia produced by four-vessel occlusion (4-VO) trigg ers the delayed death of CA1 neurons in the hippocampus, resulting in behav ioral deficits of spatial learning performance. We demonstrate that CA1 neu ronal loss induced by 4-VO (12 min) is preceded by a selective and marked e levation of catalytically active caspase-3 in these neurons, indicative of apoptosis. Virally mediated overexpression of the anti-apoptotic gene X chr omosome-linked inhibitor of apoptosis protein (XIAP) prevented both the pro duction of catalytically active caspase-3 and degeneration of CAI neurons a fter transient forebrain ischemia. CA1 neurons protected in this manner app eared to function normally, as assessed by immunohistochemical detection of the neuronal activity marker nerve growth factor inducible-a and by spatia l learning performance in the Morris water maze. These findings indicate th at caspase-3 activation is a key event in ischemic neuronal death and that blockade of this event by XIAP overexpression permits CA1 neurons to surviv e and operate properly after an ischemic insult.