Intracellular calcium overload in a model of quinolinic acid neurotoxicity in organotypic culture of rat hippocampus; inhibited by nimodipine.
The ultrastructural studies of intracellular calcium localization were performed in a model of quinolinic acid (QUIN) neurotoxicity in vitro. The calcium overload was investigated in organotypic culture of rat hippocampus exposed to QUIN or treated simultaneously with QUIN plus calcium channels blocker-nimodipine. For electron microscopy, the cultures were processed using the oxalate-pyroantimonate cytochemical technique in order to visualize the electron-dense calcium pyroantimonate granules. QUIN application induced massive accumulation of calcium deposits in damaged mitochondria of degenerating pyramidal neurons and swollen postsynaptic dendrites. Nimodipine exerted the potent neuroprotective effect against QUIN neurotoxicity accompanied by significant inhibition of intracellular calcium accumulation. However, in the glial cells, the presence of calcium precipitates was found both in the cultures exposed to QUIN alone and in those treated simultaneously with QUIN plus nimodipine. The present studies support the concept of calcium contribution in excitotoxic neuronal damage and suggest the significant role of calcium channel blockers in prevention of QUIN-induced mitochondrial calcium overload.
Matyja
E
E
Department of Neuropathology, Polish Academy of Sciences, Warszawa.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007424:Intracellular Fluid / Q000737:chemistry; D017136:Ion Transport / Q000187:drug effects; D008854:Microscopy, Electron; D008928:Mitochondria / Q000737:chemistry; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009457:Neuroglia / Q000737:chemistry / Q000648:ultrastructure; D009474:Neurons / Q000737:chemistry / Q000648:ultrastructure; D009553:Nimodipine / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D018690:Excitatory Amino Acid Agonists; D009419:Nerve Tissue Proteins; D004533:Egtazic Acid; D009553:Nimodipine; D017378:Quinolinic Acid; D002118:Calcium