Antidegenerative effects of Mg(2+)-valproate in cultured cerebellar neurons.
We have investigated in the present study the effect of Mg(2+)-valproate on necrotic degeneration induced by an excitotoxic insult in primary culture of cerebellar neurons, that is an homogeneous population of glutamatergic neurons. Mg(2+)-valproate protected cultures against glutamate-induced neurotoxicity, acting as an indirect N-methyl-D-aspartate (NMDA) receptor antagonist, thus reducing free radical formation and affecting the biochemical parameters (i.e. 45Ca(2+)-influx, cyclic GMP formation, inositol phospholipid hydrolysis and protein kinase C translocation) that undergo modifications following NMDA receptor activation in cerebellar granule cells.
Bruno
V
V
Institute of Pharmacology, University of Catania, Italy.
Sortino
M A
MA
Scapagnini
U
U
Nicoletti
F
F
Canonico
P L
PL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000737:chemistry / Q000187:drug effects*; D006152:Cyclic GMP / Q000032:analysis / Q000096:biosynthesis; D005609:Free Radicals / Q000032:analysis; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D008274:Magnesium / Q000032:analysis / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000187:drug effects*; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects*; D009498:Neurotoxins / Q000096:biosynthesis; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D046249:Transfer RNA Aminoacylation / Q000187:drug effects; D014635:Valproic Acid / Q000032:analysis / Q000494:pharmacology*
D005609:Free Radicals; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D014635:Valproic Acid; D006152:Cyclic GMP; D008274:Magnesium; D002118:Calcium