NEUROTOXIC EFFECTS OF NEONATAL TRIETHYLTIN (TET) EXPOSURE ARE EXACERBATED WITH AGING

Neonatal Long-Evans rats dosed with TET (5 mg/kg; IP) or saline on pos tnatal day (PND) 10 were examined across the life span for neural dama ge and performance on spatial learning tasks. A subset of rats were sa crificed to assess early damage with Nissl-staining, Timm's histochemi stry, and glial fibrillary acidic protein (GFAP) immunohistochemistry 2, 7, or 14 days after dosing. Littermates were tested behaviorally in a T-maze spatial delayed alternation task on PND 23 or PND 90, and in a Morris water maze place learning task at 3, 12, or 24 months postdo sing and then sacrificed for histological analysis. In neonatal rats, histological analysis indicated gliosis in discrete cortical regions, loss of Nissl-stained neurons in the hippocampal formation, entorhinal cortex and piriform cortex, and loss of Timm's staining in the entorh inal cortex. The behavioral assessment at PND 23 indicated a significa nt impairment in the T-maze. However, no significant impairments were observed in the T-maze at 3 months or the water maze at 3 or 12 months postdosing. At 24 months, TET-treated rats showed significant deficit s in acquisition and retention of the water maze task compared with ag e-matched controls. Both groups of 24 months old rats were significant ly impaired compared with young controls. At 24 months, there was a ge neral age-related decrease in the optical density of Timm's staining i n cortical regions (9%), compounded by a further decrease in the entor hinal cortex and outer molecular Layer of the dentate gyrus of the hip pocampus in TET treated rats (30%). These data indicate that early dev elopmental exposure to an organometal resulted in morphological damage that was apparent behaviorally only during early postnatal developmen t and with advanced aging.