N-terminal tripeptide of IGF-1 (GPE) prevents the loss of TH positive neurons after 6-OHDA induced nigral lesion in rats.

Abstract

The effect of the N-terminal tripeptide of insulin-like growth factor (IGF)-1, glycine-proline-glutamate (GPE), as a neuroprotective agent for nigro-striatal dopaminergic neurons was examined in the present study using a rat model of Parkinson's disease. A unilateral nigro-striatal lesion was induced in rats by injecting 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle (MFB). GPE (3 microgram) or its vehicle was administered intracerebroventricularly (i.c.v.) 2 h after the 6-OHDA lesion. Tyrosine-hydroxylase (TH) immunohistochemistry in the substantia nigra compacta (SNc) and the striatum were examined 2 weeks after the lesion. Following 6-OHDA injection, the number of TH immunopositive neurons in the ipsilateral SNc was reduced. The density of TH immunostaining was also reduced in the ipsilateral SNc and the striatum. Treatment with a single dose of GPE (n=9) significantly prevented the loss of TH immunopositive neurons (p<0. 001) and restored the TH immunoreactivity in both the SNc and the striatum compared with the vehicle control group (n=9, p<0.001). The results suggest that GPE showed promise as a potential treatment for Parkinson's disease.

• Authors: J Guan, R Krishnamurthi, H J Waldvogel, R L Faull, R Clark, P Gluckman
• Journal: Brain research (Brain Res) Vol. 859 Issue 2 Pg. 286-92 (Mar 24 2000) ISSN: 0006-8993 [Print] Netherlands
• PMID: 10719076 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Oligopeptides
• Sympatholytics
• Insulin-Like Growth Factor I
• Oxidopamine
• Tyrosine 3-Monooxygenase
• Dopamine
• glycyl-prolyl-glutamic acid

Topics

• Animals
• Cell Count
• Denervation
• Dopamine (metabolism)
• Immunohistochemistry
• Insulin-Like Growth Factor I (chemistry)
• Male
• Nerve Degeneration (drug therapy, physiopathology)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology)
• Oligopeptides (pharmacology)
• Oxidopamine
• Parkinson Disease (drug therapy, physiopathology)
• Rats
• Rats, Wistar
• Substantia Nigra (drug effects, pathology, physiopathology)
• Sympatholytics
• Tyrosine 3-Monooxygenase (analysis, metabolism)