TRIMETHYLTIN INTOXICATION INDUCES MARKED CHANGES IN NEUROPEPTIDE EXPRESSION IN THE RAT HIPPOCAMPUS

In situ hybridization and immunocytochemistry were applied to investig ate changes in the expression of somatostatin, neuropeptide Y, neuroki nin B, cholecystokinin, dynorphin, and Met-enkephalin in the rat hippo campus after administration of a single peroral dose of trimethyltin h ydroxide 9 mg/kg). Two time intervals were investigated: 5 days after trimethyltin treatment, when CA3 damage becomes manifest and is associ ated wit increased aggression, seizure susceptibility,and memory defic it, and 16 days after trimethyltin, when neuronal damage is almost max imal and seizure susceptibility is declining. Robust but transient inc reases of neuropeptide Y, neurokinin B, and Met-enkephalin mRNA levels were revealed in the granule cell layer of the dentate gyrus and incr eased neuropeptide Y and neurokinin B immunoreactivities were found in mossy fibers. IN reverse, dynorphin mRNA and immunoreactivity were de creased transiently in the dentate gyrus and moss fibers, respectively . Strong over-expression of NPY mRNA was also observed in hilar intern eurons and in CA1 and CA3 pyramidal cells as well as in the cortex at 5 days postdosing. Cholecystokinin- or neurokinin B-containing basket cells were preserved, while somatostatin-bearing inter-neurons were da maged by trimethyltin exposure. These neurochemical changes induced by trimethyltin intoxication strikingly parallel to those observed in an imal models of temporal lobe epilepsy and may reflect activation of en dogenous protective mechanisms. It is also suggested that hilar intern eurons respond differently to trimethyltin exposure, for which neurope ptides are valuable markers. Synapse 29:333-342, 1998. (C) 1998 Wiley- Liss, Inc.