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

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Author

  • 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

Summary, in English

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.

Publishing year

2014

Language

English

Pages

1-8

Publication/Series

Peptides

Volume

54

Issue

Jan 7

Document type

Journal article

Publisher

Elsevier

Topic

  • Neurosciences

Status

Published

Research group

  • Neurobiology

ISBN/ISSN/Other

  • ISSN: 1873-5169