Dysregulation of intracellular Ca2+ homeostatis is responsible for neuronal death in an experimental model of selective hippocampal degeneration induced by trimethyltin

Roberto Piacentini, Sabrina Ceccariglia, Gian Battista Azzena, Claudio Grassi, Carlo Gangitano, Fabrizio Michetti, Aurora Del Fà

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

Abstract

Trimethyltin (TMT) intoxication is considered a suitable experimental model to study the molecular basis of selective hippocampal neurodegeneration as that occurring in several neurodegenerative diseases. We have previously shown that rat hippocampal neurons expressing the Ca(2+)-binding protein calretinin (CR) are spared by the neurotoxic action of TMT hypothetically owing to their ability to buffer intracellular Ca(2+) overload. The present study was aimed at determining whether intracellular Ca(2+) homeostasis dysregulation is involved in the TMT-induced neurodegeneration and if intracellular Ca(2+)-buffering mechanisms may exert a protective action in this experimental model of neurodegeneration. In cultured rat hippocampal neurons, TMT produced time- and concentration-dependent [Ca(2+)](i) increases that were primarily due to Ca(2+) release from intracellular stores although Ca(2+) entry through Ca(v)1 channels also contributed to [Ca(2+)](i) increases in the early phase of TMT action. Cell pre-treatment with the Ca(2+) chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) (2 muM) significantly reduced the TMT-induced neuronal death. Moreover, CR(+) neurons responded to TMT with smaller [Ca(2+)](i) increases. Collectively, these data suggest that the neurotoxic action of TMT is mediated by Ca(2+) homeostasis dysregulation, and the resistance of hippocampal neurons to TMT (including CR(+) neurons) is not homogeneous among different neuron populations and is related to their ability to buffer intracellular Ca(2+) overload.
Lingua originaleEnglish
pagine (da-a)2109-2121
Numero di pagine13
RivistaJournal of Neurochemistry
Stato di pubblicazionePubblicato - 2008

Keywords

  • CALRETININ
  • RAT HIPPOCAMPAL NEURONS
  • TMT
  • calcium dysomehostatis
  • confocal calcium imaging
  • neurodegeneration

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