Pyrethroid pesticide-induced alterations in dopamine transporter function

Journal Article · Wed Mar 15 04:00:00 EST 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2005.06.003· OSTI ID:20783442

Elwan, Mohamed A ^[1]; Richardson, Jason R ^[1]; Guillot, Thomas S ^[1]; Caudle, W Michael ^[1]; Miller, Gary W ^[2]

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1. Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322 (United States)
2. Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322 (United States) and Department of Environmental and Occupational Health, School of Medicine, Emory University, Atlanta, GA 30322 (United States)

Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal dopaminergic pathway. Several epidemiological studies have demonstrated an association between pesticide exposure and the incidence of PD. Studies from our laboratory and others have demonstrated that certain pesticides increase levels of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for dopaminergic neurotoxins. Here, we report that repeated exposure (3 injections over 2 weeks) of mice to two commonly used pyrethroid pesticides, deltamethrin (3 mg/kg) and permethrin (0.8 mg/kg), increases DAT-mediated dopamine uptake by 31 and 28%, respectively. Using cells stably expressing DAT, we determined that exposure (10 min) to deltamethrin and permethrin (1 nM-100 {mu}M) had no effect on DAT-mediated dopamine uptake. Extending exposures to both pesticides for 30 min (10 {mu}M) or 24 h (1, 5, and 10 {mu}M) resulted in significant decrease in dopamine uptake. This reduction was not the result of competitive inhibition, loss of DAT protein, or cytotoxicity. However, there was an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 h. These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD.

• OSTI ID: 20783442
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 3 Vol. 211; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
DOPAMINE
IN VIVO
MICE
NERVE CELLS
NERVOUS SYSTEM DISEASES
PESTICIDES
PROTEINS
TOXICITY
UPTAKE