title: Trimethyltin-induced neuronal damage in the rat brain: comparative studies using silver degeneration stains, immunocytochemistry and immunoassay for neuronotypic and gliotypic proteins.
abstract: Trimethyltin is a neurotoxicant which produces a distinct pattern of neuronal cell death following peripheral administration of a single dose (8 mg/kg, i.p.) in rats. The cupric-silver degeneration stain was used to produce an atlas documenting the distribution and time course of trimethyltin-induced neuronal damage in adult, male Long-Evans rats. Animals were examined at survival times of 1, 2, 3, 4, 5, 7, 10 and 18 days after intoxication. The earliest degeneration was observed at day 1 in the intermediate and ventral divisions of the lateral septal nucleus, followed by development of degeneration on days 2-4 in neuron populations including the septohippocampal nucleus, septohypothalamic nucleus, anterior olfactory nucleus, bed nucleus of the stria terminalis, endopiriform nucleus, parafascicular nucleus, superior colliculus, interstitial nucleus of the posterior commissure, inferior colliculus, pontine nuclei, raphe nuclei, pars caudalis of the spinal trigeminal nucleus, the caudal aspect of nucleus tractus solitarius, dorsal vagal motor nucleus, granule cells in the dentate gyrus, pyramidal cells in CA fields of the hippocampus, and of neurons in the subiculum, pyriform cortex, entorhinal cortex and neocortex (mainly layer Vb and VI). This was followed by degenerative changes on days 5-7 in other structures, including the amygdaloid nuclei, the ventral posterolateral and ventral posteromedial thalamic nuclei and the periaqueductal gray. The distribution of terminal degeneration from these neurons indicate that specific pools of cells are affected in each structure, and the time course suggests somatofugal degeneration. The trimethyltin damage was also assessed with immunocytochemical visualization of a neuronotypic protein, protein-O-carboxyl methyltransferase and a radioimmunoassay for glial fibrillary acidic protein. Protein-O-carboxyl methyltransferase immunoreactivity was altered in neuronal populations damaged by trimethyltin, but did not appear to be either as sensitive or selective an assay of neuronal damage as the silver stain, especially at short survival times. Glial fibrillary acidic proteins were dramatically elevated 21 days after trimethyltin intoxication, particularly in areas of extensive damage. These studies revealed advantages and problems encountered in the use of each technique in assessing neurotoxic effects, forming a basis for discussion of the relative merits of using a battery of specific molecular probes for neurotoxicity evaluations.
authors: Department of Anatomy, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
authors: C D
authors: CD
authors: Balaban
authors: J P
authors: JP
authors: O'Callaghan
authors: M L
authors: ML
authors: Billingsley
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D011497:Protein O-Methyltransferase / Q000378:metabolism; D051381:Rats; D012834:Silver; D013194:Staining and Labeling; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014298:Trimethyltin Compounds / Q000633:toxicity*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D014220:Trialkyltin Compounds; D014298:Trimethyltin Compounds; C046488:trimethyltin; D012834:Silver; D011497:Protein O-Methyltransferase