title: Transplantation of NSC-derived cholinergic neuron-like cells improves cognitive function in APP/PS1 transgenic mice.
abstract: The ability to selectively control the differentiation of neural stem cells (NSCs) into cholinergic neurons in vivo would be an important step toward cell replacement therapy. First, green fluorescent protein (GFP)-NSCs were induced to differentiate into cholinergic neuron-like cells (CNLs) with retinoic acid (RA) pre-induction followed by nerve growth factor (NGF) induction. Then, these CNLs were transplanted into bilateral hippocampus of APP/PS1 transgenic mice. Behavioral parameters showed by Morris water maze (MWM) tests and the percentages of GFP-labeled cholinergic neurons of CNL transplanted mice were compared with those of controls. Brain levels of choline acetyltransferase (ChAT) mRNA and proteins were analyzed by quantitative real-time PCR and Western blotting, ChAT activity and acetylcholine (ACh) concentration were also evaluated by ChAT activity and ACh concentration assay kits. Immunofluorescence analysis showed that 80.3±1.5% NSCs differentiated into CNLs after RA pre-induction followed by NGF induction in vitro. Three months after transplantation, 82.4±6.3% CNLs differentiated into cholinergic neurons in vivo. APP/PS1 mice transplanted with CNLs showed a significant improvement in learning and memory ability compared with control groups at different time points. Furthermore, CNLs transplantation dramatically increased in the expressions of ChAT mRNA and protein, as well ChAT activity and ACh concentration in APP/PS1 mice. Our findings support the prospect of using NSC-derived CNLs in developing therapies for Alzheimer's disease (AD).
authors: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai 200065, China.
authors: G
authors: G
authors: Gu
authors: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai 200065, China.
authors: W
authors: W
authors: Zhang
authors: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai 200065, China.
authors: M
authors: M
authors: Li
authors: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai 200065, China.
authors: J
authors: J
authors: Ni
authors: Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, Shanghai 200065, China. Electronic address: pjwang_tongji@sina.com.
authors: P
authors: P
authors: Wang
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D059329:Cholinergic Neurons / Q000502:physiology / Q000637:transplantation*; D003072:Cognition Disorders / Q000503:physiopathology / Q000628:therapy*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*; D055495:Neurogenesis / Q000502:physiology; D058225:Plaque, Amyloid / Q000503:physiopathology / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D065852:Spatial Memory / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D006023:Glycoproteins; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase; D015720:5'-Nucleotidase; C412794:NT5C3A protein, human; D000109:Acetylcholine
keywords: Alzheimer’s disease; cholinergic neuron-like cells; nerve growth factor; neural stem cells; retinoic acid; transplantation