Abstract

? Both genetic and environmental factors play key roles in the pathological manifestation of Parkinson's Disease (PD). Epidemiological studies have identified pesticide exposure as a specific risk factor for PD. Our lab and others have shown that the commonly used pesticide, deltamethrin, alters the expression and function of the dopamine transporter in adult mice. The dopamine transporter is a key regulator of dopaminergic neurotransmission and a gateway for dopaminergic toxins, such as MPTP. Thus, alteration of its function or expression may increase the susceptibility of dopamine neurons to damage by neurotoxins such as MPTP and the neurotransmitter dopamine by increasing their uptake into dopamine neurons. We now provide evidence that gestational and lactational exposure to deltamethrin at levels lower than used in the adult studies leads to long-term up-regulation of the dopamine transporter. Therefore, the purpose of this study is to examine the effects of deltamethrin on the development of the nigrostriatal dopamine system and to determine if such exposures increase the susceptibility of these animals to the parkinsonism-inducing neurotoxin MPTP. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32ES013457-01
Application #
6837243
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Shreffler, Carol K
Project Start
2004-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2005-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost

  Institution

Name
Emory University
Department
Neurology
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Guillot, T S; Richardson, J R; Wang, M Z et al. (2008) PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity. Neuropeptides 42:423-34
Richardson, Jason R; Caudle, W Michael; Wang, Min Zheng et al. (2008) Developmental heptachlor exposure increases susceptibility of dopamine neurons to N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)in a gender-specific manner. Neurotoxicology 29:855-63
Guillot, Thomas S; Shepherd, Kennie R; Richardson, Jason R et al. (2008) Reduced vesicular storage of dopamine exacerbates methamphetamine-induced neurodegeneration and astrogliosis. J Neurochem 106:2205-17
Hamill, Cecily E; Caudle, W Michael; Richardson, Jason R et al. (2007) Exacerbation of dopaminergic terminal damage in a mouse model of Parkinson's disease by the G-protein-coupled receptor protease-activated receptor 1. Mol Pharmacol 72:653-64
Ramachandiran, Sampath; Hansen, Jason M; Jones, Dean P et al. (2007) Divergent mechanisms of paraquat, MPP+, and rotenone toxicity: oxidation of thioredoxin and caspase-3 activation. Toxicol Sci 95:163-71
Hatcher, Jaime M; Richardson, Jason R; Guillot, Thomas S et al. (2007) Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system. Exp Neurol 204:619-30
Caudle, W Michael; Richardson, Jason R; Wang, Min Z et al. (2007) Reduced vesicular storage of dopamine causes progressive nigrostriatal neurodegeneration. J Neurosci 27:8138-48
Sherer, Todd B; Richardson, Jason R; Testa, Claudia M et al. (2007) Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson's disease. J Neurochem 100:1469-79
Richardson, Jason R; Caudle, W Michael; Guillot, Thomas S et al. (2007) Obligatory role for complex I inhibition in the dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Toxicol Sci 95:196-204
Richardson, Jason R; Caudle, W Michael; Wang, Minzheng et al. (2006) Developmental exposure to the pesticide dieldrin alters the dopamine system and increases neurotoxicity in an animal model of Parkinson's disease. FASEB J 20:1695-7

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