Neuroprotective effects of neurokinin receptor one agonist septide in dopaminergic neurons in primary culture

Abstract

Parkinson´s disease is a serious motor disorder and it is caused by a degeneration of dopaminergic neurons in the substantia nigra pars compacta. Neurokinins (NK) are a group of neuropeptides that are suggested to be involved in the pathogenesis of Parkinson´s disease. Functions of NKs are mediated by NK receptors. Substance P, the natural ligand of NK1 receptor, is found to have neuroprotective effects on dopaminergic neurons. Septide is a selective NK1 receptor agonist. In order to investigate the neuroprotective effect of septide in vitro, septide (1uM) was co-incubated with 6-hydroxydopamine (6-OHDA, 200uM) in primary cell cultures of neonatal rat dopaminergic neurons. After 25 h, massive neuronal cell death was observed in those cultures incubated with 6-OHDA, whereas in septide co-incubation cultures most neurons were seen to be intact. By flow cytometric analysis, 17.03 ± 2.13 % of tyrosine hydroxylase (TH)-immunoreactive neurons were found to survive after co-incubation treatment but only 4.92 ± 1.40 % of TH-positive neurons were found to survive after 6-OHDA treatment. In addition, double immunofluorescence revealed that the level of TH immunoreactivity was also reduced in the surviving neurons after 6-OHDA treatment. No significant reduction of TH immunoreactivity was found in neurons co-incubated with septide and 6-OHDA. The present results indicate that septide has neuroprotective effects on dopaminergic neurons in culture. Activation of NK1 receptor by septide may have implications in treatment of Parkinson´s disease. Supported by Joint Research Scheme, National Natural Science Foundation of China and Research Grants Council of Hong Kong, 30218002 and N_HKBU202/02