title: Enhanced dopamine transporter activity in middle-aged Gdnf heterozygous mice.
abstract: Glial cell line-derived neurotrophic factor (GDNF) supports the viability of midbrain dopamine (DA) neurons that degenerate in Parkinson's disease. Middle-aged, 12 month old, Gdnf heterozygous (Gdnf(+/-)) mice have diminished spontaneous locomotor activity and enhanced synaptosomal DA uptake compared with wild type mice. In this study, dopamine transporter (DAT) function in middle-aged, 12 month old Gdnf(+/-) mice was more thoroughly investigated using in vivo electrochemistry. Gdnf(+/-) mice injected with the DAT inhibitor, nomifensine, exhibited significantly more locomotor activity than wild type mice. In vivo electrochemistry with carbon fiber microelectrodes demonstrated enhanced clearance of DA in the striatum of Gdnf(+/-) mice, suggesting greater surface expression of DAT than in wild type littermates. Additionally, 12 month old Gdnf(+/-) mice expressed greater D(2) receptor mRNA and protein in the striatum than wild type mice. Neurochemical analyses of striatal tissue samples indicated significant reductions in DA and a faster DA metabolic rate in Gdnf(+/-) mice than in wild type mice. Altogether, these data support an important role for GDNF in the regulation of uptake, synthesis, and metabolism of DA during aging.
authors.affiliation: Department of Anatomy and Neurobiology, Morris K. Udall Parkinson's Disease Research, Center of Excellence, University of Kentucky Medical Center, 306 Davis Mills Bldg, 800 Rose St., Lexington, KY 40536, USA.
authors.forename: Ofelia M
authors.initials: OM
authors.lastname: Littrell
authors.forename: Francois
authors.initials: F
authors.lastname: Pomerleau
authors.forename: Peter
authors.initials: P
authors.lastname: Huettl
authors.forename: Stewart
authors.initials: S
authors.lastname: Surgener
authors.forename: Jacqueline F
authors.initials: JF
authors.lastname: McGinty
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Middaugh
authors.forename: Ann-Charlotte
authors.initials: AC
authors.lastname: Granholm
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boger
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D017448:Receptors, Dopamine D2; D004298:Dopamine