Enhanced survival and morphological features of basal forebrain cholinergic neurons in vitro: Role of neurotrophins and other potential cortically derived cholinergic trophic factors

The present study examined survival- and growth-enhancing effects of cortic al cells on basal forebrain cholinergic neurons (BFCNs) in culture and the degree to which endogenous nerve growth factor (NGF), brain-derived neurotr ophic factor (BDNF), and neurotrophin-3 (NT-3) contribute to those trophic effects. When fetal (17 days of gestation) basal forebrain (BF) cells were grown for 5 days in coculture with cortical neurons, staining for acetylcho linesterase (AChE) showed a threefold increase in the number of BFCNs relat ive to BF cultures without cortex. Most of these labeled cells also display ed enhanced somatic, dendritic, and axonal growth. Coculturing cortical neu rons with BF cells taken from postnatal animals produced similar results bu t with a somewhat greater degree of morphologic enhancement. Function-neutr alizing antibodies to NCF, BDNF. and NT-3 were employed to determine whethe r they would block the trophic effects of cortical neurons on postnatal BFC Ns. Although no significant changes in numbers or morphological features of AChE( +) neurons were observed with treatment with individual antibodies, cocultures treated with a combination of all three antibodies displayed few er morphologically enhanced AChE(+) cells and more nonenhanced cells; the t otal number of AChE(+) neurons was not significantly changed. Treatment of pure BF cultures with exogenous NGF, BDNF, and NT-3 increased the number of AChE(+) neurons but did not reproduce the morphologic enhancement of corti cal cells on BFCNs. These results suggest that neurotrophins by themselves can increase survival of postnatal BFCNs in culture and may work in concert with other unknown cortically derived factors to enhance BFCN morphologic differentiation. The unidentified cortical factors may also have strong sur vival-enhancing effects on BFCNs that are independent of the known neurotro phins. J. Comp. Neurol. 406:156-170, 1999. (C) 1999 Wiley-Liss, Inc.