Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease

• Published in: The FASEB journal Vol. 20; no. 10; pp. 1695 - 1697
• Main Authors: Richardson, Jason R, Caudle, W. Michael, Wang, Minzheng, Dean, E. Danielle, Pennell, Kurt D, Miller, Gary W
• Format: Journal Article
• Language: English
• Published: United States The Federation of American Societies for Experimental Biology 01-08-2006; Federation of American Societies for Experimental Biology
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - administration & dosage; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology; Animals; Animals, Newborn; Dieldrin - administration & dosage; Dieldrin - pharmacology; Disease Models, Animal; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - analysis; Dopamine Plasma Membrane Transport Proteins - genetics; dopamine transporter; Drug Synergism; Female; Lactation; Male; Mice; MPTP; Neurotoxicity Syndromes - etiology; Parkinson Disease, Secondary - chemically induced; Parkinson Disease, Secondary - etiology; pesticides; Pesticides - pharmacology; Pregnancy; RNA, Messenger - analysis; Vesicular Monoamine Transport Proteins - analysis; Vesicular Monoamine Transport Proteins - genetics; vesicular monoamine transporter 2; α-synuclein
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.06-5864fje

Exposure to pesticides has been suggested to increase the risk of Parkinson's disease (PD), but the mechanisms responsible for this association are not clear. Here, we report that perinatal exposure of mice during gestation and lactation to low levels of dieldrin (0.3, 1, or 3 mg/kg every 3 days) alters dopaminergic neurochemistry in their offspring and exacerbates MPTP toxicity. At 12 wk of age, protein and mRNA levels of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT2) were increased by perinatal dieldrin exposure in a dose-related manner. We then administered MPTP (2x10 mg/kg s.c) at 12 wk of age and observed a greater reduction of striatal dopamine in dieldrin-exposed offspring, which was associated with a greater DAT:VMAT2 ratio. Additionally, dieldrin exposure during development potentiated the increase in GFAP and α-synuclein levels induced by MPTP, indicating increased neurotoxicity. In all cases there were greater effects observed in the male offspring than the female, similar to that observed in human cases of PD. These data suggest that developmental exposure to dieldrin leads to persistent alterations of the developing dopaminergic system and that these alterations induce a "silent" state of dopamine dysfunction, thereby rendering dopamine neurons more vulnerable later in life.--Richardson, J. R., Caudle, W. M., Wang, M., Dean, E. D., Pennell, K. D., Miller, G. W. Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease.