Effects of behaviorally active ACTH (4–10) analogue – Semax on rat basal forebrain cholinergic neurons

摘要

Abstract. PURPOSE. It is well established that cholinergic neurons of the basal forebrain degenerate in Alzheimer’s dementia.nAlthough recent studies were concentrated on screening molecules that might reduce the concomitant cell loss, little is knownnabout therapeutically promising molecules. We studied the effect of Semax (Met-Glu-His-Phe-Pro-Gly-Pro), a behaviorallynactive adrenocorticotropic hormone (4–10) analogue, on survival of cholinergic basal forebrain neurons in vitro. Semax is knownnto stimulate learning and memory and can be successfully used for treatment of ischemic stroke. METHODS. Primary culturesnof neuronal and glial cells from basal forebrain of rats were used in all experiments. The stability of Semax in cell cultures wasntested by HPLC analysis. Cell survival in neuronal cultures was quantitated using immocytochemical and cytochemical analysesnas well as detection of choline acetyltransferase activity. RESULTS. We have shown that Semax may approximately 1.5–1.7nfold increase survival of cholinergic basal forebrain neurons in vitro. Moreover, Semax (100 nM) stimulated activity of cholinenacetyltransferase in dissociated basal forebrain tissue cultures. However, the numbers of GABA-ergic neurons, total neuronnspecific enolase neurons were not affected. In concentration from 1 nM to 10 μM, Semax did not affect proliferation of glial cellsnin primary cultures. CONCLUSION. Implications of these findings with respect to Alzheimer’s disease remain to be clarified.