Changes in neurobiological parameters in the hippocampus after exposure to trimethyltin.

The effects of trimethyltin (TMT) on neurotransmitters, morphological changes and physiological activity of the hippocampus were studied. A single injection of TMT (8 mg/kg) decreased the high affinity uptake of glutamate (HA-Glu), which is a marker for glutamergic nerve terminals, after 7 days. The maximal reduction of HA-Glu was 42% and was obtained on postinjection day 21. Glutamate decarboxylase (GAD) and choline acetyltransferase (ChAT), markers for GABAergic and cholinergic structures, were not affected. The electrical activity of the hippocampus recorded through chronically implanted electrodes was altered by day three postinjection. The amplitude of the hippocampal electrographic record gradually decreased and the EEG ceased to be correlated with the rats' behavioral state. Fink-Heimer staining showed degenerating neurons within the subiculum, CA1, ventral CA3 and CA4 hippocampal subfields. TMT (3 mg/kg) injected once a week for three weeks decreased the HA-Glu significantly 21 days after the first injection. The HA-Glu was reduced by a maximum of 68%. The activity of ChAT was slightly increased only at day 35 postinjection while the GAD activity was not significantly reduced over a 21 day period beginning on day 14. Fink-Heimer staining showed degeneration of nerve cells within the CA1, ventral CA3 and CA4 hippocampal subfields. Both injection schedules produced degenerating neurons in the entorhinal cortex. The neurons of the dorsal CA3 region and the granule cells of the dentate gyrus were not lesioned by either TMT injection. The relationship between the behavioral, physiological and neurochemical changes induced by TMT will be discussed.