title: Paraquat is excluded by the blood brain barrier in rhesus macaque: An in vivo pet study.
abstract: Environmental factors have long been thought to have a role in the etiology of idiopathic Parkinson's disease (PD). Since the discovery of the selective neurotoxicity of MPTP to dopamine cells, suspicion has focused on paraquat, a common herbicide with chemical structure similar to 1-methyl-4-phenylpyridinium (MPP+), the MPTP metabolite responsible for its neurotoxicity. Although in vitro evidence for paraquat neurotoxicity to dopamine cells is well established, its in vivo effects have been ambiguous because paraquat is di-cationic in plasma, which raises questions about its ability to cross the blood brain barrier. This study assessed the brain uptake of [(11)C]-paraquat in adult male rhesus macaques using quantitative PET imaging. Results showed minimal uptake of [(11)C]-paraquat in the macaque brain. The highest concentrations of paraquat were seen in the pineal gland and the lateral ventricles. Global brain concentrations including those in known dopamine areas were consistent with the blood volume in those structures. This acute exposure study found that paraquat is excluded from the brain by the blood brain barrier and thus does not readily support the causative role of paraquat exposure in idiopathic Parkinson's disease.
authors.affiliation: Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, 1005 Wisconsin Institutes of Medical Research, 1111 Highland Avenue, Madison, WI 53705, USA.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Bartlett
authors.forename: James E
authors.initials: JE
authors.lastname: Holden
authors.forename: R Jerome
authors.initials: RJ
authors.lastname: Nickles
authors.forename: Dhanabalan
authors.initials: D
authors.lastname: Murali
authors.forename: David L
authors.initials: DL
authors.lastname: Barbee
authors.forename: Todd E
authors.initials: TE
authors.lastname: Barnhart
authors.forename: Bradley T
authors.initials: BT
authors.lastname: Christian
authors.forename: Onofre T
authors.initials: OT
authors.lastname: DeJesus
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002250:Carbon Radioisotopes; D007091:Image Processing, Computer-Assisted; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009498:Neurotoxins / Q000493:pharmacokinetics*; D010269:Paraquat / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography
chemical_list: D002250:Carbon Radioisotopes; D009498:Neurotoxins; D010269:Paraquat