Calbindin overexpression buffers hippocampal cultures from the energetic impairments caused by glutamate

A dramatic rise in free cytosolic calcium concentration is thought to be a central event in the pathogenesis of glutamate excitotoxicity in neurons. W e have previously demonstrated that gene transfer of the calcium-binding pr otein calbindin D28k via a Herpes simplex amplicon vector decreases the ris e in intracellular calcium and promotes cell survival following glutamaterg ic challenge, This study explores the effect of calbindin trans.-ene expres sion on cellular metabolism following glutamate excitotoxicity. Because exc itotoxic. insults are often energetic in nature, and because calcium seques tering and extrusion place heavy energy demands on a cell, we hypothesized that calbindin overexpression may help preserve cellular energy levels duri ng an insult. We overexpressed calbindin in primary hippocampal cultures, u sing a Herpes simplex amplicon vector system. We found that calbindin overe xpression protected neurons from the decline in ATP levels, mitochondrial p otential and metabolic rate following a glutamatergic insult. These results indicate that calbindin expression helps preserve cellular energy state fo llowing glutamate excitotoxicity. This illustrates the energetic load place d on neurons by increased free cytosolic calcium and may help explain the n europrotective effects of calbindin. (C) 2001 Elsevier Science BY All right s reserved.