title: Glutamate-induced differential mitochondrial response in young and adult rats.
abstract: Excitatory amino acid glutamate is involved in neurotransmission in the nervous system but it becomes a potent neurotoxin under variety of conditions. However, the molecular mechanism of excitotoxicity is not known completely. We have studied the influence of glutamate on intracellular calcium and mitochondrial functions in cortical slices from young and adult rats. The slices from both the age groups exhibited comparable intracellular calcium changes upon glutamate stimulation. Glutamate treatment caused a decrease in adenosine 5'-diphosphate/adenosine 5'-triphosphate (ADP/ATP) and an increase in nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide reduced form (NAD/NADH) ratio in both the age groups but the magnitude and the nature of temporal change was different. Glutamate-induced decrease in ATP/ADP and increase in NAD/NADH ratio was significantly higher in slices from the adult as compared to the young rats. The slices from young rats elicited slightly higher mitochondrial depolarization than adult rats. However, the formation of reactive oxygen species (ROS) and lactate dehydrogenase (LDH) release were significantly higher in adult rats as compared to young rats. Glutamate-induced mitochondrial depolarization, ROS formation and LDH release were highly dependent on the presence of Ca(2+) in the extracellular medium. The treatment of slices with mitochondrial inhibitors rotenone and oligomycin inhibited ROS formation and LDH release substantially. Our results suggest that the glutamate-induced increase in intracellular calcium is not the only factor responsible for neuronal cell death but the mitochondrial functions could be crucial in excitotoxicity.
authors.affiliation: Department of Biophysics, National Institute of Mental Health and Neuro Sciences, Bangalore 560 029, India.
authors.forename: S S
authors.initials: SS
authors.lastname: Kannurpatti
authors.forename: B G
authors.initials: BG
authors.lastname: Sanganahalli
authors.forename: Sudha
authors.initials: S
authors.lastname: Mishra
authors.forename: Preeti G
authors.initials: PG
authors.lastname: Joshi
authors.forename: N B
authors.initials: NB
authors.lastname: Joshi
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005456:Fluorescent Dyes; D016257:Fura-2; D018698:Glutamic Acid / Q000494:pharmacology*; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects*; D009243:NAD / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D009243:NAD; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D007770:L-Lactate Dehydrogenase; D002118:Calcium; D016257:Fura-2