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Dysregulation of intracellular calcium homeostasis is responsible for neuronal death in an experimental model of selective hippocampal degeneration induced by trimethyltin
Author(s) -
Piacentini Roberto,
Gangitano Carlo,
Ceccariglia Sabrina,
Fà Aurora Del,
Azzena Gian Battista,
Michetti Fabrizio,
Grassi Claudio
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05297.x
Subject(s) - neurodegeneration , hippocampal formation , intracellular , neuroscience , chemistry , neuron , calcium in biology , homeostasis , microbiology and biotechnology , biology , medicine , biochemistry , disease
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 μM) 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.