Publication
Young Human Cholinergic Neurons Respond to Physiological Regulators and Improve Cognitive Symptoms in an Animal Model of Alzheimer's Disease.
Morelli Annamaria, Sarchielli Erica, Guarnieri Giulia, Coppi Elisabetta, Pantano Daniela, Comeglio Paolo, Nardiello Pamela, Pugliese Anna M, Ballerini Lara, Matucci Rosanna, Ambrosini Stefano, Castronovo Giuseppe, Valente Rosa, Mazzanti Benedetta, Bucciantini Sandra, Maggi Mario, Casamenti Fiorella, Gallina Pasquale, Vannelli Gabriella B
Abstract
The degeneration of cholinergic neurons of the nucleus basalis of Meynert (NBM) in the basal forebrain (BF) is associated to the cognitive decline of Alzheimer's disease (AD) patients. To date no resolutive therapies exist. Cell-based replacement therapy is a strategy currently under consideration, although the mechanisms underlying the generation of stem cell-derived NBM cholinergic neurons able of functional integration remain to be clarified. Since fetal brain is an optimal source of neuronal cells committed towards a specific phenotype, this study is aimed at isolating cholinergic neurons from the human fetal NBM (hfNBMs) in order to study their phenotypic, maturational and functional properties. Extensive characterization confirmed the cholinergic identity of hfNBMs, including positivity for specific markers (such as choline acetyltransferase) and acetylcholine (Ach) release. Electrophysiological measurements provided the functional validation of hfNBM cells, which exhibited the activation of peculiar sodium (I