Interferon-gamma promotes cholinergic differentiation of embryonic septal nuclei and adjacent basal forebrain.

ABSTRACT

In cultured rat embryonic septal nuclei with adjacent basal forebrain, murine interferon-gamma (IFN gamma) produces a striking increase in choline acetyltransferase (ChAT) activity and mRNA. The effect of IFN gamma on cholinergic differentiation is more potent in E14 cultures than in older cultures. IFN gamma does not cause a change in the affinity of ChAT for choline, nor does it affect cell proliferation. Whereas IFN gamma doubles neuronal cell number, the cholinergic cell number increases more than 7-fold. Ameboid microglia respond to IFN gamma with the translocation of p91 to the nucleus. The action of IFN gamma is not mediated by NGF or bFGF. The enhancement of cholinergic expression that occurs with increased cell density may be partly attributable to an endogenous IFN gamma-like molecule, since antibodies to IFN gamma offset the effects of increased cell density.