Enhanced survival and morphological features of basal forebrain cholinergic neurons in vitro: Role of neurotrophins and other potential cortically derived cholinergic trophic factors
Dh. Ha et al., Enhanced survival and morphological features of basal forebrain cholinergic neurons in vitro: Role of neurotrophins and other potential cortically derived cholinergic trophic factors, J COMP NEUR, 406(2), 1999, pp. 156-170
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.