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

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.

• Authors: Roberto Piacentini, Carlo Gangitano, Sabrina Ceccariglia, Aurora Del Fà, Gian Battista Azzena, Fabrizio Michetti, Claudio Grassi
• Journal: Journal of neurochemistry (J Neurochem) Vol. 105 Issue 6 Pg. 2109-21 (Jun 01 2008) ISSN: 1471-4159 [Electronic] England
• PMID: 18284612 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Trimethyltin Compounds
• trimethyltin

Topics

• Animals
• Calcium Signaling (drug effects, physiology)
• Cell Death (drug effects, physiology)
• Cells, Cultured
• Disease Models, Animal
• Hippocampus (drug effects, physiology)
• Homeostasis (drug effects, physiology)
• Intracellular Fluid (drug effects, metabolism, physiology)
• Nerve Degeneration (chemically induced, metabolism, pathology)
• Neurons (drug effects, metabolism, physiology)
• Rats
• Rats, Wistar
• Trimethyltin Compounds (toxicity)