Journal
PEPTIDES
Volume 54, Issue -, Pages 1-8Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2013.12.007
Keywords
Dopamine; Glial cell line-derived neurotrophic factor; Parkinson's disease; Striatum; Peptide
Funding
- National Center for Research Resources [5P20RR016481-12]
- National Institute of General Medical Sciences [8 P20 GM103436-12]
- National Center for Research Resources
- National Center for Advancing Translational Sciences
- National Institutes of Health [UL1TR000117]
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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. (c) 2014 Elsevier Inc. All rights reserved.
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