title: Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro.
abstract: Glial cell-line derived neurotrophic factor (GDNF) has demonstrated robust effects on dopamine (DA) neuron function and survival. A post-translational processing model of the human GDNF proprotein theorizes the formation of smaller, amidated peptide(s) from the proregion that exhibit neurobiological function, including an 11-amino-acid peptide named dopamine neuron stimulating peptide-11 (DNSP-11). A single treatment of DNSP-11 was delivered to the substantia nigra in the rat to investigate effects on DA-neuron function. Four weeks after treatment, potassium (K+) and D-amphetamine evoked DA release were studied in the striatum using microdialysis. There were no significant changes in DA-release after DNSP-11 treatment determined by microdialysis. Dopamine release was further examined in discrete regions of the striatum using high-speed chronoamperometry at 1-, 2-, and 4-weeks after DNSP-11 treatment. Two weeks after DNSP-11 treatment, potassium-evoked DA release was increased in specific subregions of the striatum. However, spontaneous locomotor activity was unchanged by DNSP-11 treatment. In addition, we show that a single treatment of DNSP-11 in the MN9D dopaminergic neuronal cell line results in phosphorylation of ERK1/2, which suggests a novel cellular mechanism responsible for increases in DA function.
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Fuqua
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA.
authors.forename: Ofelia M
authors.initials: OM
authors.lastname: Littrell
authors.affiliation: Experimental Medical Science, Neurobiology, Lund University, BMCA11, 221, 84 Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Lundblad
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Turchan-Cholewo
authors.affiliation: Department of Molecular & Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA; Center of Structural Biology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Lina G
authors.initials: LG
authors.lastname: Abdelmoti
authors.affiliation: Department of Molecular & Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA; Center of Structural Biology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Emilia
authors.initials: E
authors.lastname: Galperin
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA; Department of Molecular & Cellular Biochemistry, University of Kentucky College of Medicine, Lexington, KY, USA; Center of Structural Biology, University of Kentucky College of Medicine, Lexington, KY, USA.
authors.forename: Luke H
authors.initials: LH
authors.lastname: Bradley
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Cass
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA.
authors.forename: Don M
authors.initials: DM
authors.lastname: Gash
authors.affiliation: Department of Anatomy and Neurobiology, Parkinson's Disease Translational Center of Excellence, University of Kentucky Medical Center, MN 206 Medical Sciences Building, 800 Rose St., Lexington, KY 40536, USA. Electronic address: greg.gerhardt@uky.edu.
authors.forename: Greg A
authors.initials: GA
authors.lastname: Gerhardt
mesh_terms: D000818:Animals; D002460:Cell Line / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D066328:Ventral Striatum / Q000187:drug effects / Q000378:metabolism
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D009842:Oligopeptides; D010446:Peptide Fragments; C000597541:prolyl-prolyl-glutamyl-alanyl-prolyl-alanyl-glutamyl-aspartyl-arginyl-seryl-leucinamide; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D004298:Dopamine
keywords: Dopamine; Glial cell line-derived neurotrophic factor; Parkinson's disease; Peptide; Striatum