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

Joshua L. Fuqua, Ofelia M. Littrell, Martin Lundblad, Jadwiga Turchan-Cholewo, Lina G. Abdelmoti, Emilia Galperin, Luke H. Bradley, Wayne A. Cass, Don M. Gash, Greg A. Gerhardt

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalPeptides
Volume54
DOIs
StatePublished - Apr 2014

Bibliographical note

Funding Information:
GAG: USPHS NS39787 ; AG13494 ; NSF EEC-0310723 ; NIH Training Grants : 5T32 AG000242-14 and 1T32 DA022738 (OML/JLF)

Funding Information:
This work is supported by funding sources:

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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