期刊
TOXICOLOGICAL SCIENCES
卷 77, 期 1, 页码 83-90出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/kfh014
关键词
developmental neurotoxicity; chlorpyrifos; choline acetyltransferase; cholinesterase inhibition; cholinergic neurochemistry; organophosphate insecticide
类别
资金
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES010386] Funding Source: NIH RePORTER
- NIEHS NIH HHS [R01 ES10386] Funding Source: Medline
The neurochemical effects in developing rats exposed during gestation to the anticholinesterase organophosphorus insecticide chlorpyrifos (CPS) were determined. Pregnant rats were dosed daily with CPS (0, 3, or 7 mg/kg) in corn oil from gestation days (GD) 6-20. Pups were euthanized on postnatal days (PND) 1, 3, 6, 9, 12, and 30 for the determination of brain cholinesterase (ChE) and choline acetyltransferase (ChAT) activities, along with muscarinic receptor (mAChR) densities, the levels of the high-affinity choline uptake (HACU) system, and the vesicular acetylcholine transporter (VAChT). ChE activities were inhibited about 15 and 30% on PND 1, in the low- and high-dosage groups, respectively, and were not different from control values by PND 6. mAChR densities on PND 1 were reduced in the high-dosage group by about 18, 21, and 17%, using H-3-N-methylscopolamine, H-3-quinuclidinyl benzilate, and H-3-4-DAMP, respectively, as ligands, and were not different from control levels by PND 6. ChAT activity was decreased by similar to12% in the high-dosage group on PND 9, 12, and 30. HACU levels, using H-3-hemicholinium-3 as the ligand, were reduced by similar to25% on PND 6 in the low- and high-dosage groups, and by similar to14 and 21% on PND 12 and 30, only in the high-dosage group. Levels of the VAChT were reduced by a range of 13-31% on PND 3 through 30 in the high-dosage group, using H-3-AH5183 (vesamicol) as the ligand. These data suggest that gestational exposure to 7 mg/kg/day CPS results in long-term alterations of presynaptic cholinergic neurochemistry.
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