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

Abstract

The present study examined survival- and growth-enhancing effects of cortical cells on basal forebrain cholinergic neurons (BFCNs) in culture and the degree to which endogenous nerve growth factor (NGF), brain-derived neurotrophic 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 acetylcholinesterase (AChE) showed a threefold increase in the number of BFCNs relative to BF cultures without cortex. Most of these labeled cells also displayed enhanced somatic, dendritic, and axonal growth. Coculturing cortical neurons with BF cells taken from postnatal animals produced similar results but with a somewhat greater degree of morphologic enhancement. Function-neutralizing antibodies to NGF, BDNF, and NT-3 were employed to determine whether they would block the trophic effects of cortical neurons on postnatal BFCNs. 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 fewer morphologically enhanced AChE(+) cells and more nonenhanced cells; the total 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 cortical 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 survival-enhancing effects on BFCNs that are independent of the known neurotrophins.

Coeloglossum viride var. bracteatum extract attenuates d-galactose and NaNO2 induced memory impairment in mice

“…NT-3, a kind of neurotrophic factor, has nutrient effect on growth and function of cholinergic neurons, which play important roles in learning and memory (Ha et al, 1999). It has also been shown to improve the impaired learning and memory function in aged rats and the lesions to cholinergic neurons (Durany et al, 2000).…”

Non-Cell-Autonomous Regulation of GABAergic Neuron Development by Neurotrophins and the p75 Receptor

“…We examined the regulation of anterior basal forebrain cholinergic and GABAergic neuron numbers by neurotrophins using a well defined in vitro system (Hartikka and Hefti, 1988;Ha et al, 1999;Lopez-Coviella et al, 2005) in which neurons from the neonatal medial septum and diagonal bands of Broca were dissociated and cultured on astrocyte monolayers. We used immunolabeling for VAChT to identify cholinergic neurons and GAD65/67 to label GABAergic neurons (Fig.…”

Chronic ketamine use increases serum levels of brain-derived neurotrophic factor

“…Neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) serve as survival factors for selected populations of central nervous system (CNS) neurons, including cholinergic and dopaminergic neurons (Lad et al 2003;Hyman et al 1991;Ha et al 1999). In addition, neurotrophins, particularly BDNF, may regulate LTP in the hippocampus (Minichiello 2009) and influence synaptic plasticity (Verpelli et al 2010).…”