Intracellular glutathione levels determine cerebellar granule neuron sensitivity to excitotoxic injury by kainic acid

• Published in: Brain research 2000-04, Vol.862 (1), p.83-89
• Main Authors: Ceccon, Maddalena, Giusti, Pietro, Facci, Laura, Borin, Gianfranco, Imbesi, Marta, Floreani, Maura, Skaper, Stephen D.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Survival - drug effects; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Cerebellum; Cerebellum - chemistry; Cerebellum - cytology; Cerebellum - metabolism; Development; Excitatory Amino Acid Agonists - toxicity; Excitatory amino acids; Fluoresceins; Fundamental and applied biological sciences. Psychology; Glutamic Acid - toxicity; Glutathione; Glutathione - analogs & derivatives; Glutathione - analysis; Glutathione - pharmacology; Kainic Acid - toxicity; N-Methylaspartate - toxicity; Nerve Degeneration - chemically induced; Nerve Degeneration - drug therapy; Nerve Degeneration - metabolism; Neurodegeneration; Neurons - chemistry; Neurons - cytology; Neurons - drug effects; Neuroprotective Agents - pharmacology; Neurotoxins - toxicity; Oxidative Stress - drug effects; Oxidative Stress - physiology; Radiation-Protective Agents - pharmacology; Rats; Rats, Sprague-Dawley; Reactive oxygen species; Reactive Oxygen Species - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(00)02074-6

Glutathione (GSH) is a key component of the cellular defence cascade against injury caused by reactive oxygen species. Kainic acid (KA) is a potent central nervous system excitotoxin. KA-elicited neuronal death may result from the generation of ROS. The present study was undertaken to characterize the role of GSH in KA-induced neurotoxicity. Cultures of cerebellar granule neurons were prepared from 8-day-old rats, and used at 8, 14 and 20 days in vitro (DIV). Granule neurons displayed a developmental increase in their sensitivity to KA injury, as quantified by an ELISA-based assay with the tetrazolium salt MTT. At DIV 14 and 20, a 30-min challenge with KA (500 μM) reduced cell viability by 45% after 24 h, significantly greater ( P