scholarly journals Overexpression of NTRK1 Promotes Differentiation of Neural Stem Cells into Cholinergic Neurons

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Limin Wang ◽  
Feng He ◽  
Zhuoyuan Zhong ◽  
Ruiyan Lv ◽  
Songhua Xiao ◽  
...  

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.

Author(s):  
Jun-Ping Pan ◽  
Yang Hu ◽  
Jia-Hui Wang ◽  
Yi-Rong Xin ◽  
Jun-Xing Jiang ◽  
...  

2014 ◽  
Vol 71 ◽  
pp. 43
Author(s):  
Ranmal A. Samarasinghe ◽  
Prasad S. Kanuparthi ◽  
J. Timothy Greenamyre ◽  
Donald B. DeFranco ◽  
Roberto DiMaio

2006 ◽  
Vol 14 (3) ◽  
pp. 237-248 ◽  
Author(s):  
Anne Schänzer ◽  
Frank-Peter Wachs ◽  
Daniel Wilhelm ◽  
Till Acker ◽  
Christiana Cooper-Kuhn ◽  
...  

Development ◽  
2017 ◽  
Vol 144 (21) ◽  
pp. 3968-3977 ◽  
Author(s):  
Stéphane Bugeon ◽  
Antoine de Chevigny ◽  
Camille Boutin ◽  
Nathalie Coré ◽  
Stefan Wild ◽  
...  

2012 ◽  
Vol 21 (11) ◽  
pp. 2487-2496 ◽  
Author(s):  
Hong J. Lee ◽  
In J. Lim ◽  
Seung W. Park ◽  
Yun B. Kim ◽  
Yong Ko ◽  
...  

Alzheimer's disease (AD) is characterized by degeneration and loss of neurons and synapses throughout the brain, causing the progressive decline in cognitive function leading to dementia. No effective treatment is currently available. Nerve growth factor (NGF) therapy has been proposed as a potential treatment of preventing degeneration of basal forebrain cholinergic neurons in AD. In a previous study, AD patient's own fibroblasts genetically modified to produce NGF were transplanted directly into the brain and protected cholinergic neurons from degeneration and improved cognitive function in AD patients. In the present study, human neural stem cells (NSCs) are used in place of fibroblasts to deliver NGF in ibotenic acid-induced learning-deficit rats. Intrahippocampal injection of ibotenic acid caused severe neuronal loss, resulting in learning and memory deficit. NGF protein released by F3.NGF human NSCs in culture medium is 10-fold over the control F3 naive NSCs at 1.2 μg/106 cells/day. Overexpression of NGF in F3.NGF cells induced improved survival of NSCs from cytotoxic agents H2O2, Aβ, or ibotenic acid in vitro. Intrahippocampal transplantation of F3.NGF cells was found to express NGF and fully improved the learning and memory function of ibotenic acid-challenged animals. Transplanted F3.NGF cells were found all over the brain and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs overexpressing NGF improve cognitive function of learning-deficit model mice.


Stem Cells ◽  
2012 ◽  
Vol 30 (12) ◽  
pp. 2657-2671 ◽  
Author(s):  
Carlo Cusulin ◽  
Emanuela Monni ◽  
Henrik Ahlenius ◽  
James Wood ◽  
Jan Claas Brune ◽  
...  

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ana Marin Navarro ◽  
Robin Johan Pronk ◽  
Astrid Tjitske van der Geest ◽  
Ganna Oliynyk ◽  
Ann Nordgren ◽  
...  

AbstractIn this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Furthermore, a reduced proliferation rate, downregulation of genes involved in oxidative phosphorylation (OXPHOS), and an upregulation of glycolytic capacity was apparent upon loss of p53. In addition, p53KD neural stem cells display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Using brain organoids, we modeled more specifically cortical neurogenesis. Here we found that p53 loss resulted in brain organoids with disorganized stem cell layer and reduced cortical progenitor cells and neurons. Similar to NES cells, neural progenitors isolated from brain organoids also show a downregulation in several OXPHOS genes. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation, as well as maintaining structural organization and proper metabolic gene profile of neural progenitors in human brain organoids.


2021 ◽  
Vol 4 (1) ◽  
pp. 23-41
Author(s):  
Alexandra-Elena Dobranici ◽  
Sorina Dinescu ◽  
Marieta Costache

Specialised cells of the brain are generated from a population of multipotent stem cells found in the forming embryo and adult brain after birth, called neural stem cells. They reside in specific niches, usually in a quiescent, non-proliferating state that maintains their reservoir. Neural stem cells are kept inactive by various cues such as direct cell-cell contacts with neighbouring cells or by soluble molecules that trigger intracellular responses. They are activated in response to injuries, physical exercise, or hypoxia condition, through stimulation of signaling pathways that are usually correlated with increased proliferation and survival. Moreover, mature neurons play essential role in regulating the balance between active and quiescent state by realising inhibitory or activating neurotransmitters. Understanding molecular mechanisms underlying neuronal differentiation is of great importance in elucidating pathological conditions of the brain and treating neurodegenerative disorders that until now have no efficient therapies.


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