Cholinergic impact on neuroplasticity drives muscarinic M1 receptor mediated differentiation into neurons.
OBJECTIVE
Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro.


METHODS
Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (BFGF) and epidermal growth factor (EGF).


RESULTS
Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF- and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons.


CONCLUSIONS
Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.
Department of Psychiatry, LMU-University of Munich, Munich, Germany. jens.benninghoff@med.uni-muenchen.de
Jens
J
Benninghoff
Werner
W
Rauh
Victor
V
Brantl
Robert J
RJ
Schloesser
Rainald
R
Moessner
Hans-Jürgen
HJ
Möller
Dan
D
Rujescu
D053687:Adult Stem Cells / Q000378:metabolism*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D018679:Cholinergic Agonists / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D058953:Neural Stem Cells / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000187:drug effects*; D010890:Pirenzepine / Q000494:pharmacology*; D043643:Receptor, Muscarinic M1 / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
D018679:Cholinergic Agonists; D018727:Muscarinic Antagonists; D043643:Receptor, Muscarinic M1; D016222:Fibroblast Growth Factor 2; D010890:Pirenzepine; D004815:Epidermal Growth Factor; D002217:Carbachol