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

• Published in: Peptides (New York, N.Y. : 1980) Vol. 54; no. Jan 7; pp. 1 - 8
• Main Authors: Fuqua, Joshua L., Littrell, Ofelia M., Lundblad, Martin, Turchan-Cholewo, Jadwiga, Abdelmoti, Lina G., Galperin, Emilia, Bradley, Luke H., Cass, Wayne A., Gash, Don M., Gerhardt, Greg A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2014
• Subjects: Animals; Basic Medicine; Cell Line - drug effects; Cellular; Dopamine; Dopamine - metabolism; Glial cell line-derived neurotrophic factor; Glial Cell Line-Derived Neurotrophic Factor - chemistry; Humans; In Vitro Techniques; In vitro testing; Male; Mathematical models; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Motor Activity - drug effects; Neurons; Neurons - drug effects; Neurons - metabolism; Neurosciences; Neurovetenskaper; Oligopeptides - pharmacology; Parkinson's disease; Peptide; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptides; Phosphorylation; Phosphorylation - drug effects; Rats, Inbred F344; Striatum; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Surgical implants; Ventral Striatum - drug effects; Ventral Striatum - metabolism; FAST-16; Glial cell line-derived neurotrophic factor; VTA; Dopamine; Parkinson's disease; DOPAC; Striatum; GFR; HVA; GDNF; PD; TH; 5-HIAA; SN; 5-HT; Peptide; DA; DNSP-11; EC; HPLC
• ISSN: 0196-9781; 1873-5169; 1873-5169
• DOI: 10.1016/j.peptides.2013.12.007

•A peptide (DNSP-11), derived from the proregion of GDNF, was investigated.•DNSP-11 was delivered to the substantia nigra to investigate in vivo effects.•DNSP-11 caused increased dopamine release in the dorsal, but not ventral, striatum.•The release effects occurred 2 weeks after treatment but not at 1- or 4-weeks.•DNSP-11 increased ERK1/2 phosphorylation in neuronal cells. 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.