About this Journal Submit a Manuscript Table of Contents 
International Journal of Peptides
Volume 2010 (2010), Article ID 537639, 10 pages
doi:10.1155/2010/537639
Research Article

Brain Activation by Peptide Pro-Leu-Gly- N H 𝟐 (MIF-1)

Reas S. Khan,1 Chuanhui Yu,1 Abba J. Kastin,1 Yi He,1 Rudolph H. Ehrensing,2 Hung Hsuchou,1 Kirsten Prufer Stone,1 and Weihong Pan1

1Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA
2The Ochsner Clinic Foundation, New Orleans, LA 70121, USA

Received 26 October 2009; Revised 12 January 2010; Accepted 13 January 2010

Academic Editor: Yvette Taché

Copyright © 2010 Reas S. Khan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

MIF-1 (Pro-Leu-Gly- N H 2 ) is a tripeptide for which the therapeutic potential in Parkinson's disease and depression has been indicated by many studies. However, the cellular mechanisms of action of MIF-1 are not yet clear. Here, we show the specific brain regions responsive to MIF-1 treatment by c-Fos mapping, and determine the kinetics of cellular signaling by western blotting of pERK, pSTAT3, and c-Fos in cultured neurons. The immunoreactivity of c-Fos was increased 4 hours after MIF-1 treatment in brain regions critically involved in the regulation of mood, anxiety, depression, and memory. The number of cells activated was greater after peripheral treatment (intravenous delivery) than after intracerebroventricular injection. In cultured SH-SY5Y neuronal cells, c-Fos was induced time- and dose-dependently. The activation of cellular c-Fos was preceded by a transient increase of mitogen-activated protein kinase pERK but a reduction of phosphorylated Signal Transducer and Activator of Transcription (pSTAT3) initially. We conclude that MIF-1 can modulate multiple cellular signals including pERK, and pSTAT3 to activate c-Fos. The cellular activation in specific brain regions illustrates the biochemical and neuroanatomical basis underlying the therapeutic effect of MIF-1 in Parkinson's disease and depression.