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Peptides. 2014 Apr;54:1-8. doi: 10.1016/j.peptides.2013.12.007. Epub 2014 Jan 7.

Dynamic changes in dopamine neuron function after DNSP-11 treatment: effects in vivo and increased ERK 1/2 phosphorylation in vitro.

Author information

1
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.
2
Experimental Medical Science, Neurobiology, Lund University, BMCA11, 221, 84 Lund, Sweden.
3
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.
4
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.
5
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.

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.

KEYWORDS:

Dopamine; Glial cell line-derived neurotrophic factor; Parkinson's disease; Peptide; Striatum

PMID:
24406899
PMCID:
PMC3989369
DOI:
10.1016/j.peptides.2013.12.007
[Indexed for MEDLINE]
Free PMC Article

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