Dysregulation of intracellular calcium homeostasis is responsible for neuronal death in an experimental model of selective hippocampal degeneration induced by trimethyltin

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

Research output: Contribution to journalArticlepeer-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 Ca2+-binding protein calretinin (CR) are spared by the neurotoxic action of TMT hypothetically owing to their ability to buffer intracellular Ca2+ overload. The present study was aimed at determining whether intracellular Ca2+ homeostasis dysregulation is involved in the TMT-induced neurodegeneration and if intracellular Ca2+-buffering mechanisms may exert a protective action in this experimental model of neurodegeneration. In cultured rat hippocampal neurons, TMT produced time- and concentration-dependent [Ca2+] i increases that were primarily due to Ca2+ release from intracellular stores although Ca2+ entry through Cav1 channels also contributed to [Ca2+]i increases in the early phase of TMT action. Cell pre-treatment with the Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) (2 μM) significantly reduced the TMT-induced neuronal death. Moreover, CR+ neurons responded to TMT with smaller [Ca2+]i increases. Collectively, these data suggest that the neurotoxic action of TMT is mediated by Ca2+ 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 Ca2+ overload.

Original languageEnglish
Pages (from-to)2109-2121
Number of pages13
JournalJournal of Neurochemistry
Volume105
Issue number6
DOIs
Publication statusPublished - Jun 2008

Keywords

  • Calcium dyshomeostasis
  • Calretinin
  • Confocal calcium imaging
  • Neurodegeneration
  • Rat hippocampal neurons
  • Trimethyltin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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