Abstract
Neurotrophic tyrosine kinase type 1 (NTRK1) plays critical roles in proliferation, differentiation, and survival of cholinergic neurons; however, it remains unknown whether enhanced expression of NTRK1 in neural stem cells (NSCs) can promote their differentiation into mature neurons. In this study, a plasmid encoding the rat NTRK1 gene was constructed and transfected into C17.2 mouse neural stem cells (NSCs). NTRK1 overexpression in C17.2 cells was confirmed by western blot. The NSCs overexpressing NTRK1 and the C17.2 NSCs transfected by an empty plasmid vector were treated with or without 100 ng/mL nerve growth factor (NGF) for 7 days. Expression of the cholinergic cell marker, choline acetyltransferase (ChAT), was detected by florescent immunocytochemistry (ICC). In the presence of NGF induction, the NSCs overexpressing NTRK1 differentiated into ChAT-immunopositive cells at 3-fold higher than the NSCs transfected by the plasmid vector (26% versus 9%, P < 0.05). The data suggest that elevated NTRK1 expression increases differentiation of NSCs into cholinergic neurons under stimulation of NGF. The approach also represents an efficient strategy for generation of cholinergic neurons.
Highlights
The family neurotrophic tyrosine receptor kinase (NTRK), known as tropomyosin receptor kinases (Trk), includes receptors regulating synaptic strength and plasticity in the mammalian nervous system [1]
The full length Neurotrophic tyrosine kinase type 1 (NTRK1) gene was stably transferred into neural stem cells
Overexpression of NTRK1 led to 3-fold higher differentiation efficiency (26% versus 9%) when subjected to stimulation by nerve growth factor (NGF)
Summary
The family neurotrophic tyrosine receptor kinase (NTRK), known as tropomyosin receptor kinases (Trk), includes receptors regulating synaptic strength and plasticity in the mammalian nervous system [1]. NTRK1 is synthesized in basal forebrain cholinergic neurons (BFCN) and displayed on their axons, where NTRK1 is bound by its primary ligand, nerve growth factor (NGF) [2, 3]. Expression of NTRK1 precedes expression of choline acetyltransferase (ChAT), the enzyme that mediates the biosynthesis of acetylcholine and serves as a marker of cholinergic neurons, during the development of central nervous system (CNS) [4, 5]. NGF produced by neocortical neurons can experimentally induce basal forebrain cells to differentiate into cholinergic cells through activation of NTRK1 [6,7,8,9,10]. NTRK1 is considered to be involved in the early neuronal development
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