Cyclin-dependent kinase 4 and cyclin D1 are required for excitotoxin-induced neuronal cell death in vivo

Authors
Citation
H. Ino et T. Chiba, Cyclin-dependent kinase 4 and cyclin D1 are required for excitotoxin-induced neuronal cell death in vivo, J NEUROSC, 21(16), 2001, pp. 6086-6094
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
16
Year of publication
2001
Pages
6086 - 6094
Database
ISI
SICI code
0270-6474(20010815)21:16<6086:CK4ACD>2.0.ZU;2-N
Abstract
Systemic administration of the glutamic acid analog kainic acid (KA) causes neuronal cell death in brain-vulnerable regions, such as the piriform cort ex, hippocampus, and amygdala in rats. We investigated the relationship bet ween the KA-induced neuronal apoptosis and expression of cyclin-dependent k inase 4 (CDK4) and cyclin D1, key regulators of cell cycle progression. Exp ression of CDK4 and cyclin D1 was upregulated in neurons of the rat pirifor m cortex and amygdala 1-3 d after KA administration in vivo. CDK4 and cycli n D1 proteins were induced in the cytoplasm and nuclei of neurons, with a c oncomitant increase of CDK4- and cyclin D1-positive microglia in the affect ed areas. Continuous infusion of 100 muM CDK4 or cyclin D1 antisense oligon ucleotides into the lateral ventricle using mini-osmotic pumps suppressed t he excitotoxin-induced neuronal cell death in the piriform cortex and basol ateral amygdaloid nucleus, whereas sense oligonucleotides exhibited no such effect. Although KA administration causes prolonged c-Fos expression in th e vulnerable regions that preceded the induction of neuronal apoptosis, the CDK4 or cyclin D1 antisense oligonucleotides exhibited no suppressive effe ct on c-Fos levels. Our results suggest that CDK4 and cyclin D1 are essenti al for KA-induced neuronal apoptosis in vivo.