Glutamate-induced differential mitochondrial response in young and adult rats

• Published in: Neurochemistry international 2004-04, Vol.44 (5), p.361-369
• Main Authors: Kannurpatti, S.S, Sanganahalli, B.G, Mishra, Sudha, Joshi, Preeti G, Joshi, N.B
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Aging - physiology; Animals; Biological and medical sciences; Calcium - metabolism; Calcium Signaling - drug effects; Cell Survival - drug effects; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cerebral Cortex - ultrastructure; Cortical slices; Excitotoxicity; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Fura-2; Glutamic Acid - pharmacology; Intracellular calcium; Intracellular Membranes - drug effects; Intracellular Membranes - metabolism; L-Lactate Dehydrogenase - metabolism; Microscopy, Fluorescence; Mitochondria - drug effects; Mitochondrial depolarization; NAD - metabolism; Neurons - drug effects; Neurons - pathology; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/S0197-0186(03)00164-5

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.