title: The angiotensin converting enzyme inhibitor captopril protects nigrostriatal dopamine neurons in animal models of parkinsonism.
abstract: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by a prominent loss of nigrostriatal dopamine (DA) neurons with an accompanying neuroinflammation. The peptide angiotensin II (AngII) plays a role in oxidative-stress induced disorders and is thought to mediate its detrimental actions via activation of AngII AT1 receptors. The brain renin-angiotensin system is implicated in neurodegenerative disorders including PD. Blockade of the angiotensin converting enzyme or AT1 receptors provides protection in acute animal models of parkinsonism. We demonstrate here that treatment of mice with the angiotensin converting enzyme inhibitor captopril protects the striatum from acutely administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrine (MPTP), and that chronic captopril protects the nigral DA cell bodies from degeneration in a progressive rat model of parkinsonism created by the chronic intracerebral infusion of 1-methyl-4-phenylpyridinium (MPP+). The accompanying activation of microglia in the substantia nigra of MPP+-treated rats was reduced by the chronic captopril treatment. These findings indicate that captopril is neuroprotective for nigrostriatal DA neurons in both acute and chronic rodent PD models. Targeting the brain AngII pathway may be a feasible approach to slowing neurodegeneration in PD.
authors.affiliation: Department of Neurology, Rutgers, The State University of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ, USA. Electronic address: sonsalla@rwjms.rutgers.edu.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Sonsalla
authors.forename: Christal
authors.initials: C
authors.lastname: Coleman
authors.forename: Lai-Yoong
authors.initials: LY
authors.lastname: Wong
authors.forename: Suzan L
authors.initials: SL
authors.lastname: Harris
authors.forename: Jason R
authors.initials: JR
authors.lastname: Richardson
authors.forename: Bharathi S
authors.initials: BS
authors.lastname: Gadad
authors.forename: Wenhao
authors.initials: W
authors.lastname: Li
authors.forename: Dwight C
authors.initials: DC
authors.lastname: German
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002216:Captopril / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018696:Neuroprotective Agents; D002216:Captopril
keywords: Angiotensin converting enzyme; Captopril; Dopamine neurodegeneration; MPP+; MPTP; Mice; Microglia; Osmotic minipump; Parkinson's disease; Rats