glycyl-prolyl-glutamic-acid and Parkinson-Disease

Central administration of N-terminal tripeptide of IGF-1 (GPE) prevents the loss of dopamine neurons. We now examine effects of GPE administered peripherally, on long-term functional recovery after 6-OHDA lesion in rats. GPE treatment (3 mg/kg, i.p.), 3 days after the lesion reduced the number of rotations (p<0.005) and the time over meter (p<0.005) compared to vehicle treatment. Step length and number of adjusting steps were increased in the GPE group (p<0.005), particularly at 12 weeks post lesion. However, GPE treatment did not prevent the loss of tyrosine hydroxylase in the substantia nigra pars compacta and the striatum. The study suggests that peripheral administration of GPE after onset of nigrostriatal dopamine depletion improves long-term Parkinsonian motor deficits, independent of neuronal outcome.

Topics: Animals; Behavior, Animal; Cell Count; Corpus Striatum; Disease Models, Animal; Dose-Response Relationship, Drug; Functional Laterality; Immunohistochemistry; Insulin-Like Growth Factor I; Male; Motor Activity; Neuroprotective Agents; Oligopeptides; Oxidopamine; Parkinson Disease; Psychomotor Performance; Rats; Rats, Wistar; Rotation; Substantia Nigra; Sympatholytics; Time Factors; Tyrosine 3-Monooxygenase

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.

Topics: Animals; Cell Count; Denervation; Dopamine; Immunohistochemistry; Insulin-Like Growth Factor I; Male; Nerve Degeneration; Neurons; Neuroprotective Agents; Oligopeptides; Oxidopamine; Parkinson Disease; Rats; Rats, Wistar; Substantia Nigra; Sympatholytics; Tyrosine 3-Monooxygenase