Trimethyltin initially activates the caspase 8/caspase 3 pathway for damaging the primary cultured cortical neurons derived from embryonic mice.

The organotin trimethyltin (TMT) is well known to cause neuronal damage in the central nervous system. To elucidate the mechanisms underlying the toxicity of TMT toward neurons, we prepared primary cultures of neurons from the neocortex of mouse embryos. A continuous exposure to TMT produced a decrease in cell viability as well as an increase in the number of cells with nuclear condensation/shrinkage at the exposure time window up to 24 hr.

High susceptibility of cortical neural progenitor cells to trimethyltin toxicity: involvement of both caspases and calpain in cell death.

Neural progenitor cells play an essential role in both the developing embryonic nervous system and in the adult brain, where the capacity for self-renewal would be important for normal brain functions. In the present study, we used embryonic cortical neural progenitor cells to investigate the effects of trimethyltin chloride (TMT) on the survival of neural progenitor cells. In cultures of cortical neural progenitor cells, the formation of round neurospheres was observed in the presence of epidermal growth factor and basic fibroblast growth factor within 9 days in vitro.

Activation of c-Jun N-terminal kinase cascades is involved in part of the neuronal degeneration induced by trimethyltin in cortical neurons of mice.

The organotin trimethyltin (TMT) is known to cause neuronal degeneration in the central nervous system. A systemic injection of TMT produced neuronal damage in the cerebral frontal cortex of mice. To elucidate the mechanism(s) underlying the toxicity of TMT toward neurons, we prepared primary cultures of neurons from the cerebral cortex of mouse embryos for use in this study.

In vivo depletion of endogenous glutathione facilitates trimethyltin-induced neuronal damage in the dentate gyrus of mice by enhancing oxidative stress.

Acute treatment with trimethyltin chloride (TMT) produces neuronal damage in the hippocampal dentate gyrus of mice. We investigated the in vivo role of glutathione in mechanisms associated with TMT-induced neural cell damage in the hippocampus by examining mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHO). In the hippocampus of animals treated with CHO 1h beforehand, a significant increase was seen in the number of single-stranded DNA-positive cells in the dentate gyrus when determined on day 2 after the injection of TMT at a dose of 2.

Decreased level of mitochondrial RNA by glutamate in cultured cortical neurons.

Mitochondrial injury is induced by a decline in mitochondrial function as well as by damaged mitochondrial DNA. In this study, we evaluate the effects of glutamate exposure on the level of mitochondrial mRNA in cultured cortical neurons of mice. Glutamate exposure for 15 min significantly reduced cell viability 24 h later.