title: Chronic nicotine treatment increases nAChRs and microglial expression in monkey substantia nigra after nigrostriatal damage.
abstract: Our previous work had shown that long-term nicotine administration improved dopaminergic markers and nicotinic receptors (nAChRs) in the striatum of monkeys with nigrostriatal damage. The present experiments were done to determine whether nicotine treatment also led to changes in the substantia nigra, the region containing dopaminergic cell bodies. Monkeys were chronically treated with nicotine in the drinking water for 6 months after which they were injected with low dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP) for a further 6-month period. Nicotine was administered until the monkeys were euthanized 2 months after the last MPTP injection. Nicotine treatment did not affect the dopamine transporter or the number of tyrosine hydroxylase positive cells in the substantia nigra of lesioned monkeys. However, nicotine administration did lead to a greater increase in alpha3/alpha6beta2* and alpha4beta2* nAChRs in lesioned monkeys compared to controls. Nicotine also significantly elevated microglia and reduced the number of extracellular neuromelanin deposits in the substantia nigra of MPTP-lesioned monkeys. These findings indicate that long-term nicotine treatment modulates expression of several molecular measures in monkey substantia nigra that may result in an improvement in nigral integrity and/or function. These observations may have therapeutic implications for Parkinson's disease.
authors.affiliation: The Parkinson's Institute, Sunnyvale, CA 94085, USA. mquik@parkinsonsinstitute.org
authors.forename: Maryka
authors.initials: M
authors.lastname: Quik
authors.forename: Carla
authors.initials: C
authors.lastname: Campos
authors.forename: Neeraja
authors.initials: N
authors.lastname: Parameswaran
authors.forename: J William
authors.initials: JW
authors.lastname: Langston
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Michael
authors.initials: M
authors.lastname: Yeluashvili
mesh_terms: D000818:Animals; D015415:Biomarkers; D002452:Cell Count; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008543:Melanins / Q000378:metabolism; D017628:Microglia / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009538:Nicotine / Q000494:pharmacology* / Q000627:therapeutic use; D018722:Nicotinic Agonists / Q000494:pharmacology / Q000627:therapeutic use; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000187:drug effects; D012453:Saimiri; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D015415:Biomarkers; D004298:Dopamine; D008543:Melanins; D018696:Neuroprotective Agents; D009538:Nicotine; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D014446:Tyrosine 3-Monooxygenase; C014121:neuromelanin; C403531:nicotinic receptor alpha4beta2
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