Organophosphates dysregulate dopamine signaling, glutamatergic neurotransmission, and induce neuronal injury markers in striatum

Details

• Personal Author:
  Bibb JA ; Drerup JM ; Lovinger D ; Mathur BN ; O'Callaghan JP ; Thomas R ; Torres-Altoro MI
• Description:
  The neurological effects of organophosphate pesticides, commonly used on foods and in households, are an important public health concern. Furthermore, subclinical exposure to combinations of organophosphates is implicated in Gulf War illness. Here we characterized the effects of the broadly-used insecticide chlorpyrifos on dopamine and glutamatergic neurotransmission effectors in corticostriatal motor/reward circuitry. Chlorpyrifos potentiated PKA-dependent phosphorylation of the striatal protein DARPP-32 and the GluR1 subunit of AMPA receptors in mouse brain slices. It also increased GluR1 phosphorylation by PKA when administered systemically. This correlated with enhanced glutamate release from cortical projections in rat striatum. Similar effects were induced by the sarin congener, diisopropyl fluorophosphate, alone or in combination with the putative neuroprotectant, pyridostigmine bromide and the pesticide DEET. This combination, meant to mimic the neurotoxicant exposure encountered by veterans of the 1991 Persian Gulf War, also induced hyperphosphorylation of the neurofibrillary tangle-associated protein tau. Diisopropyl fluorophosphate and pyrodostigmine bromide, alone or in combination, also increased the aberrant activity of the protein kinase, Cdk5, as indicated by conversion of its activating cofactor p35 to p25. Thus consistent with recent findings in humans and animals, organophosphate exposure causes dysregulation in the motor/reward circuitry and invokes mechanisms associated with neurological disorders and neurodegeneration. [Description provided by NIOSH]
• Subjects:
  Animals Biological Warfare Agents Hazardous Substances Insecticides Nervous System Occupational Health Organophosphates Phosphoric Acids Safety
• Keywords:
  Animal-studies Author Keywords: Insecticide Biological-warfare-agents Chlorpyrifos Dopamine Glutamates Gulf War Illness Hazardous-materials Humans Military-personnel Neurological-reactions Neurological-system Neuromotor-function Neuromotor-system Neurotoxic-effects Neurotoxicity Neurotoxins Neurotransmitters Organo-phosphorus-compounds Organo-phosphorus-pesticides Organophosphate Pesticides Phosphates Proteins Toxic-effects Toxic-materials

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• ISSN:
  0022-3042
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Maryland ; OSHA Region 3 ; OSHA Region 6 ; Texas ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  303-313
• Volume:
  119
• Issue:
  2
• NIOSHTIC Number:
  nn:20039410
• Citation:
  J Neurochem 2011 Oct; 119(2):303-313
• Contact Point Address:
  James A. Bibb, Department of Psychiatry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, NC5.410 Dallas, TX 75390-9070
• Email:
  james.bibb@utsouthwestern.edu
• CAS Registry Number:
  Chlorpyrifos (CAS RN 2921-88-2) ; Diisopropyl fluorophosphate (CAS RN 55-91-4) ; Dopamine (CAS RN 51-61-6) ; N,N-Diethyl-m-toluamide (CAS RN 134-62-3)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Neurochemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e97642a7f12f53632ddf34a9e6c934570ffef11539a5720c35a0e8fa6d2e857788661843d3183b8bc29aa2423762c248f3847f16336231e40f95020220e66dc2
• Download URL:
  https://stacks.cdc.gov/view/cdc/192705/cdc_192705_DS1.pdf
• File Type:
  [PDF - 394.92 KB ]