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a Experimental Oncology Unit—Department of Oncology, M. Ascoli, ARNAS-Civico, Palermo, Italy b Laboratory of Neurophysiology, Istituto di Ricerche Farmacologiche "Mario Negri," Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti 66030, Italy
Key Words: cerebellar granule cells • apoptosis • lyophilized red wine • ASL • mSOD1G93A
Address for correspondence: Dr. Giuseppe Carruba, Experimental Oncology Unit—Department of Oncology, P.O. M. Ascoli, ARNAS-Civico, Palermo, Italy. Voice: +39-091-6664348; fax: +39-091-6664352. e-mail: lucashbl{at}unipa.it
In this work, we have investigated the effects of nutritional antioxidants as antidegenerative agents on glutamate-induced apoptosis in primary cultures of cerebellar granule neurons (CGNs). Glutamate-induced apoptosis is also associated with intracellular [Ca2+]I overload, generation of reactive oxygen species (ROS), depression of cell energy metabolism, cytochrome c release, and increase in caspase-3 activity. Pretreatment (3 h) with red wine extract (5 µg/mL) and ascorbic acid (30 µM) blocks glutamate-induced apoptosis in CGNs. In vivo experiments carried out on transgenic mice expressing the human mutated Cu, Zn superoxide dismutase (SOD1) G93A (mSOD1G93A) show that mice fed with lyophilized red wine have significantly increased survival as compared to control, untreated animals.
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