Semax prevents the death of tyrosine hydroxylase-positive neurons in a mixed neuroglial cell culture derived from the embryonic rat mesencephalon in a model of 6-hydroxydopamine-induced neurotoxicity

Abstract

The peptide Semax (MEHFPGP), which is an analogue of the ACTH (4–10) fragment, has a wide spectrum of activity in the nervous system of mammals, including humans. Using a model of neurotoxicity induced by hydroxydopamine, we studied the ability of Semax to prevent the death of tyrosine hydroxylase-positive neurons in a primary mixed neuroglial cell culture derived from the mesencephalon of rat embryos. We found that the application of 6-hydroxydopamine at concentrations of 2 and 5 µM to the culture medium induced a dose-dependent loss of tyrosine hydroxylase-positive neurons by 25 and 65%, respectively. The application of Semax at a concentration of 0.1 µM 30 min prior to treatment with 5 µM 6-hydroxydopamine significantly increased the number of tyrosine hydroxylase-positive neurons by 30–40%. Addition of Semax to cell cultures 24 h prior to the neurotoxin did not reveal the protective effect of the peptide. These data show that Semax may potentially be used for the treatment of some neurodegenerative diseases that are associated with a loss of dopaminergic neurons in the CNS.