N-terminal tripeptide of IGF-I improves functional deficits after 6-OHDA lesion in rats

Central administration of N-terminal tripeptide of IGF-I (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.