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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Line / drug effects
  • Dopamine / metabolism*
  • Glial Cell Line-Derived Neurotrophic Factor / chemistry*
  • Humans
  • In Vitro Techniques
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Motor Activity / drug effects
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oligopeptides / pharmacology*
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Phosphorylation / drug effects
  • Rats, Inbred F344
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Ventral Striatum / drug effects
  • Ventral Striatum / metabolism

Substances

  • Glial Cell Line-Derived Neurotrophic Factor
  • Oligopeptides
  • Peptide Fragments
  • prolyl-prolyl-glutamyl-alanyl-prolyl-alanyl-glutamyl-aspartyl-arginyl-seryl-leucinamide
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Dopamine