Quinolinate-induced rat striatal excitotoxicity impairs endoplasmic reticulum Ca2+-ATPase function.
Excessive activation of NMDA glutamate receptors and the resulting loss of intracellular Ca(2+) homeostasis may be lethal (excitotoxic) to neurons. Such excitotoxicity can be induced in vivo by intrastriatal infusion of quinolinate, as this substance selectively activates NMDA receptors. The aim of the present research was to investigate whether the in vivo treatment of striatal tissue with quinolinate would lead to an early impairment of sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) activity or mitochondrial Ca(2+) sequestration, two intracellular mechanisms involved in Ca(2+) homeostasis and signaling. Sodium quinolinate was infused intrastriatally into adult rats, and 6 h later the brains were removed and the corpora striata dissected. At this time point, striatal sections stained with Fluoro-Jade, a cellular marker of cell death, showed initial signs of neuronal degeneration. In addition, SERCA activity decreased 39% in relation to the activity observed in the control striata. A corresponding decrease of the same magnitude in (45)Ca(2+) uptake by striatal microsomes was also found in the treated striata. Western blot analysis did not indicate any decrease in SERCA levels in striatal tissue after quinolinate infusion. Mitochondrial Ca(2+) sequestration was still preserved in quinolinate-treated striatal tissue when the assay was carried out in the presence of physiological concentrations of ATP and Mg(2+). These results suggest that impairment of the SERCA function may be an early event in excitotoxicity.
Fernandes
Anna M A P
AM
Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, CP 6111, Campinas, SP, 13083-887, Brazil. annamabr@yahoo.com.br
Landeira-Fernandez
Ana M
AM
Souza-Santos
Patrícia
P
Carvalho-Alves
Paulo C
PC
Castilho
Roger F
RF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects*; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis; D008928:Mitochondria / Q000378:metabolism; D009498:Neurotoxins / Q000494:pharmacology*; D017378:Quinolinic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*
D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D017378:Quinolinic Acid; D002118:Calcium