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

The effect of the N-terminal tripeptide of insulin-like growth factor (IGF) -1, glycine-proline-glucamate (GPE), as a neuroprotective agent for nigro-s triatal dopaminergic neurons was examined in the present study using a rat model of Parkinson's disease. A unilateral nigro-striatal lesion was induce d in rats by injecting 6-hydroxydopamine (6-OHDA) into the right medial for ebrain bundle (MFB). GPE (3 mu g) or its vehicle was administered intracere broventricularly (i.c.v.) 2 h after the 6-OHDA lesion. Tyrosine-hydroxylase (TH) immunohistochemistry in the substantia nigra compacta (SNc) and the s triatum 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 t he TH immunoreactivity in both the SNc and the striatum compared with the v ehicle control group (n = 9, p < 0.001). The results suggest that GPE showe d promise as a potential treatment for Parkinson's disease. (C) 2000 Elsevi er Science B.V. All rights reserved.