Neural stem cell transplants improve cognitive function without altering amyloid pathology in an APP/PS1 double transgenic model of Alzheimer's disease.
Neural stem cells (NSCs) are capable of self-renewal and are multipotent. Transplantation of NSCs may represent a promising approach for treating neurodegenerative disorders associated with cognitive decline, such as Alzheimer disease (AD) characterized by extensive loss of neurons. In this study, we investigated the effect of NSC transplantation on cognitive function in the amyloid precursor protein/presenilin-1 (APP/PS1) transgenic mouse, an AD mouse model with age-dependent cognitive deficits. We found that NSCs bilaterally transplanted into hippocampal regions improved spatial learning and memory function in these mice, but did not alter Aβ pathology. Immunohistochemical analyses determined that NSCs proliferated, migrated, and differentiated into three neuronal cell types. The improvement in cognitive function was correlated with enhanced long-term potentiation (LTP) and an increase in the neuron expression of proteins related to cognitive function: N-methyl-D-aspartate (NMDA) 2B unit, synaptophysin (SYP), protein kinase C ζ subtypes (PKCζ), tyrosine receptor kinase B (TrkB), and brain-derived neurotrophic factor (BDNF). Taken together, our data indicated that injected NSCs can rescue cognitive deficits in APP/PS1 transgenic mice by replacing neuronal cell types expressing multiple cognition-related proteins that enhance LTP.
Department of Medical Imaging, Tongji Hospital, Medical School of Tongji University, No. 389 Xincun Road, Putuo District, Shanghai, 200065, China.
Wei
W
Zhang
Pei-Jun
PJ
Wang
Hong-ying
HY
Sha
Jiong
J
Ni
Ming-hua
MH
Li
Guo-jun
GJ
Gu
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003071:Cognition / Q000502:physiology; D004195:Disease Models, Animal; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D058953:Neural Stem Cells / Q000166:cytology* / Q000637:transplantation; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D033581:Stem Cell Transplantation
D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D053764:Presenilin-1; C580804:presenilin 1, mouse