High potassium and cyclic AMP analog promote neuronal survival of basal forebrain cholinergic neurons in culture from postnatal 2-week-old rats

Abstract

We found depolarization-dependent promotion of survival of cultured basal forebrain cholinergic neurons from postnatal 2-week-old rats. Over 30 mM KCl (high K +) as well as nerve growth factor (NGF) induced considerably high choline acetyltransferase (ChAT) activity and the increase was potentiated by the addition of BAY K8644, a Ca 2+ channel agonist. The increase in ChAT activity by high K + was due to the increased number of viable acetylcholinesterase-positive and ChAT-positive neurons. Also, a cyclic AMP analog gave the same effect as high K +, but its ability to induce the ChAT activity was higher than that of high K +. On the other hand, both high K + and NGF had very little effects on the survival of the cultured cholinergic neurons from 10-week-old rats. Cyclic AMP analog induced considerable increase in ChAT activity and promotion of survival of cholinergic neurons in the 10-week-old culture. These findings showed that the neuronal death occurring just of the end of synapse formation in rat basal forebrain cholinergic neurons could be prevented by NGF and high K +, but the death of older cholinergic neurons could not. We propose the possibility that the death of postnatal 2-week-old basal forebrain cholinergic neurons in culture might be programmed cell death.