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

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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. © 2008 The Authors.
Lingua originaleEnglish
pagine (da-a)2109-2121
Numero di pagine13
RivistaJournal of Neurochemistry
Volume105
DOI
Stato di pubblicazionePubblicato - 2008

Keywords

  • Animals
  • Calcium Signaling
  • Calcium dyshomeostasis
  • Calretinin
  • Cell Death
  • Cells, Cultured
  • Confocal calcium imaging
  • Disease Models, Animal
  • Hippocampus
  • Homeostasis
  • Intracellular Fluid
  • Nerve Degeneration
  • Neurodegeneration
  • Neurons
  • Rat hippocampal neurons
  • Rats
  • Rats, Wistar
  • Trimethyltin
  • Trimethyltin Compounds

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