Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures.

Détails

ID Serval
serval:BIB_1FA20A41EF54
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures.
Périodique
Developmental Brain Research
Auteur(s)
Honegger P., Pardo B., Monnet-Tschudi F.
ISSN
0165-3806 (Print)
ISSN-L
0165-3806
Statut éditorial
Publié
Date de publication
1998
Volume
105
Numéro
2
Pages
219-225
Langue
anglais
Résumé
During brain development, spontaneous neuronal activity has been shown to play a crucial role in the maturation of neuronal circuitries. Activity-related signals may cause selective neuronal cell death and/or rearrangement of neuronal connectivity. To study the effects of sustained inhibitory activity on developing inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal rat telencephalon were used. In relatively immature cultures, muscimol (10 microns), a GABAA receptor agonist, induced a transient increase in apoptotic cell death, as evidenced by a cycloheximide-sensitive increase of free nucleosomes and an increased frequency of DNA double strand breaks (TUNEL labeling). Furthermore, muscimol caused an irreversible reduction of glutamic acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol-induced death of GABAergic neurons was attenuated by the GABAA receptor blockers bicuculline (100 microns) and picrotoxin (100 microns), by depolarizing potassium concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644 (2 microns). As compared to the cholinergic marker (choline acetyltransferase activity), glutamic acid decarboxylase activity was significantly more affected by various agents known to inhibit neuronal activity, including tetrodotoxin (1 micron), flunarizine (5 microns), MK 801 (50 microns) and propofol (40 microns). The present results suggest that the survival of a subpopulation of immature GABAergic neurons is dependent on sustained neuronal activity and that these neurons may undergo apoptotic cell death in response to GABAA autoreceptor activation.
Mots-clé
Animals, Brain/cytology, Brain/drug effects, Cell Aggregation/drug effects, Cell Death/drug effects, Cells, Cultured, DNA Fragmentation/drug effects, GABA Agonists/toxicity, GABA-A Receptor Agonists, Muscimol/toxicity, Neurons/drug effects, Neurons/enzymology, Nucleosomes/enzymology, Nucleosomes/ultrastructure, Rats, Rats, Sprague-Dawley, gamma-Aminobutyric Acid/physiology
Pubmed
Web of science
Création de la notice
24/01/2008 13:11
Dernière modification de la notice
20/08/2019 12:55
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