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Developmental and behavioral toxicity following acute postnatal exposure of rat pups to trimethyltin
Insights
Postnatal exposure to trimethyltin hydroxide (TMT) in rats caused long-term neurodevelopmental and behavioral changes. These included impaired growth, altered motor activity, and reduced startle responses, alongside decreased brain weight.
Area of Science:
- Neuroscience
- Toxicology
- Developmental Biology
Background:
- Trialkyltin compounds are known neurotoxicants.
- Developmental exposure can lead to lasting neurological deficits.
Purpose of the Study:
- To investigate the long-term neurodevelopmental toxicity of trimethyltin hydroxide (TMT) following acute postnatal exposure in rats.
Main Methods:
- Rat pups were administered a single intraperitoneal injection of TMT (0, 4, 5, or 6 mg/kg) on postnatal day 5.
- Behavioral assessments included milk band size, growth, rope descent, motor activity, and acoustic startle response.
- Brain weights (whole brain, olfactory bulbs, hippocampus) were measured in adulthood.
Main Results:
- TMT exposure reduced milk band size, growth, and preweaning motor performance.
- Adult rats exhibited increased motor activity and altered acoustic startle responses.
- Significant reductions in whole brain, olfactory bulb, and hippocampal weights were observed.
Conclusions:
- Acute postnatal TMT exposure induces persistent neurodevelopmental and behavioral alterations in rats.
- These findings highlight the vulnerability of the developing nervous system to TMT toxicity.
- TMT exposure results in long-lasting functional and structural changes in the brain.
Abstract:
The purpose of this study was to extend our investigations on the developmental neurotoxicity of trialkyltin compounds. On postnatal day 5 (PND 5), rat pups received a single intraperitoneal injection of either 0 (saline), 4, 5 or 6 mg/kg trimethyltin hydroxide (TMT) calculated as the base. The size of the milk bands was decreased in 6 mg/kg TMT pups 48-96 hr after dosing, while in 5 mg/kg TMT pups, milk bands were reduced 96 hr after dosing only. Dosages of 5 and 6 mg/kg TMT reduced growth and impaired performance in rope descent during the preweaning period. As adults, motor activity in figure-eight mazes was increased for 6 mg/kg TMT animals. The startle response to an acoustic stimulus (a 13 kHz, 120 dB tone) was also affected by TMT when measured both during ontogeny and in adulthood. During development, on days 10-21, both 5 and 6 mg/kg TMT reduced the number of responses during 30-trial sessions for both males and females. Amplitudes were decreased for the 5 and 6 mg/kg dose on days 12-13, and for all dosages on days 18-19 and 20-21. Startle amplitude of adults was decreased at all dosages for males but not for females. These behavioral changes were accompanied by decreases in adult brain weight for both sexes. Whole brain weight and weight of the olfactory bulbs were decreased following all dosages of TMT, while hippocampal weight was decreased following both 5 and 6 mg/kg TMT. These results indicate that acute postnatal exposure to TMT produces long-term effects on the nervous system and behavior.