Related Experiment Videos
Pyrethroid pesticide-induced alterations in dopamine transporter function
Mohamed A Elwan1, Jason R Richardson, Thomas S Guillot
1Center for Neurodegenerative Disease, School of Medicine, Emory University, Atlanta, GA 30322, USA.
Toxicology and Applied Pharmacology
|July 12, 2005
Summary
Exposure to pyrethroid pesticides like deltamethrin and permethrin may increase dopamine transporter (DAT) levels in the brain, potentially raising the risk for Parkinson's disease (PD). This pesticide-induced DAT increase could make dopamine neurons more vulnerable to neurotoxins.
Area of Science:
- Neuroscience
- Toxicology
- Environmental Health
Background:
- Parkinson's disease (PD) is linked to pesticide exposure.
- Pesticide exposure may alter dopamine transporter (DAT) levels, impacting dopaminergic neurotransmission.
- DAT is crucial for dopamine uptake and neurotoxin entry into neurons.
Purpose of the Study:
- To investigate the effects of pyrethroid pesticides (deltamethrin, permethrin) on DAT function and dopamine neuron vulnerability.
- To determine if in vivo pesticide exposure up-regulates DAT.
- To explore the cellular mechanisms underlying pesticide-induced changes in DAT.
Main Methods:
- Mice were exposed to deltamethrin and permethrin.
- DAT-mediated dopamine uptake was measured in vivo and in cell cultures.
- Dopamine transporter protein levels, inhibition, cytotoxicity, and apoptosis were assessed.
Main Results:
- In vivo exposure to deltamethrin and permethrin increased DAT-mediated dopamine uptake.
- Short-term in vitro exposure did not affect DAT uptake, but prolonged exposure decreased it.
- Reduced dopamine uptake was associated with increased DNA fragmentation, indicating apoptosis, not competitive inhibition or cytotoxicity.
Conclusions:
- In vivo pyrethroid pesticide exposure indirectly up-regulates DAT.
- Long-term in vitro pesticide exposure induces apoptosis in cells expressing DAT.
- DAT up-regulation by these pesticides may enhance dopamine neuron susceptibility to neurotoxic insults, potentially contributing to PD pathogenesis.