Acupuncture accelerates neural regeneration and synaptophysin production after neural stem cells transplantation in mice

BACKGROUND Synaptophysin plays a key role in synaptic development and plasticity of neurons and is closely related to the cognitive process of Alzheimer’s disease(AD)patients.Exogenous neural stem cells(NSCs)improve the damaged nerve function.The effects of Sanjiao acupuncture on cognitive impairment may be related to the regulation of the NSC microenvironment.AIM To explore the anti-dementia mechanism of acupuncture by regulating the NSC microenvironment.METHODS NSCs were isolated from pregnant senescence-accelerated mouse resistant 1(SAMR1)mice,labeled with BrdU,and injected into the hippocampus of senescence-accelerated mouse prone 8(SAMP8)mice.Eight-month-old senescence-accelerated mice(SAM)were randomly divided into six groups:SAMR1(RC),SAMP8(PC),sham transplantation(PS),NSC transplantation(PT),NSC transplantation with acupuncture(PTA),and NSC transplantation with nonacupoint acupuncture(PTN).Morris water maze test was used to study the learning and memory ability of mice after NSC transplantation.Hematoxylin-eosin staining and immunofluorescence were used to observe the histopathological changes and NSC proliferation in mice.A co-culture model of hippocampal slices and NSCs was established in vitro,and the synaptophysin expression in the hippocampal microenvironment of mice was observed by flow cytometry after acupuncture treatment.RESULTS Morris water maze test showed significant cognitive impairment of learning and memory in 8-mo-old SAMP8,which improved in all the NSC transplantation groups.The behavioral change in the PTA group was stronger than those in the other two groups(P<0.05).Histopathologically,the hippocampal structure was clear,the cell arrangement was dense and orderly,and the necrosis of cells in CA1 and CA3 areas was significantly reduced in the PTA group when compared with the PC group.The BrdU-positive proliferating cells were found in NSC hippocampal transplantation groups,and the number increased significantly in the PTA group than in the PT and PTN groups(P<0.05).Flow cytometry showed that after co-culture of NSCs with hippocampal slices in vitro,the synaptophysin expression in the PC group decreased in comparison to the RC group,that in PT,PTA,and PTN groups increased as compared to the PC group,and that in the PTA group increased significantly as compared to the PTN group with acupointrelated specificity(P<0.05).CONCLUSION Acupuncture may promote nerve regeneration and synaptogenesis in SAMP8 mice by regulating the microenvironment of NSC transplantation to improve the nerve activity and promote the recovery of AD-damaged cells.

Stem cell therapy for Alzheimer's disease

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by memory loss and cognitive impairment.It is caused by synaptic failure and excessive accumulation of misfolded proteins.To date,almost all advanced clinical trials on specific AD-related pathways have failed mostly due to a large number of neurons lost in the brain of patients with AD.Also,currently available drug candidates intervene too late.Stem cells have improved characteristics of self-renewal,proliferation,differentiation,and recombination with the advent of stem cell technology and the transformation of these cells into different types of central nervous system neurons and glial cells.Stem cell treatment has been successful in AD animal models.Recent preclinical studies on stem cell therapy for AD have proved to be promising.Cell replacement therapies,such as human embryonic stem cells or induced pluripotent stem cell–derived neural cells,have the potential to treat patients with AD,and human clinical trials are ongoing in this regard.However,many steps still need to be taken before stem cell therapy becomes a clinically feasible treatment for human AD and related diseases.This paper reviews the pathophysiology of AD and the application prospects of related stem cells based on cell type.