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Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer’s Disease Treated with Hippocampal Neural Stem Cells

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Abstract

Transplantation with neural stem cells (NSCs) is a promising clinical therapy for Alzheimer’s disease (AD). However, the final fate of grafted NSCs is mainly determined by the host microenvironment. Therefore, this study investigated the role of Sanjiao acupuncture in the NSCs-treated hippocampus of a mouse model, senescence-accelerated mouse prone 8 (SAMP8) using Western blot, real-time fluorescent PCR, and immunofluorescence techniques. Meanwhile, we developed a co-culture model of hippocampal tissue specimens and NSCs in vitro, to observe the effects of acupuncture on survival, proliferation and differentiation of grafted NSCs using flow cytometry. Results showed that acupuncture pre- and post-NSCs transplantation significantly improved senescence-induced cognitive dysfunction (P < 0.05); upregulated the expression of basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and brain-derived neurotrophic factor (BDNF) (P < 0.05); and also increased the count of neuron-specific nuclear protein (NeuN)- and glial fibrillary acidic protein (GFAP)-positive cells (P < 0.05). Therapeutic acupuncture may regulate the cytokine levels associated with survival, proliferation, and differentiation of NSCs in hippocampal microenvironment, to promote the repair of damaged cells, resulting in improved cognitive performance in mice.

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Abbreviations

NSCs:

Neural stem cells

AD:

Alzheimer’s disease

SAMP8:

Senescence-accelerated mouse prone 8

SAMR1:

Senescence-accelerated mouse resistance 1

EGF:

Epidermal growth factor

bFGF:

Basic fibroblast growth factor

NeuN:

Neuron-specific nuclear protein

GFAP:

Glial fibrillary acidic protein

BrdU:

Bromodeoxyuridine

DG:

Dentate gyrus

RC:

SAMR1 control group

PC:

SAMP8 control group

PS:

SAMP8 sham operation group

PT:

SAMP8 NSCs transplantation group

PTA:

SAMP8 NSCs transplantation with acupoint group

PTN:

SAMP8 NSCs transplantation with non-acupoint group

BDNF:

Brain-derived neurotrophic factor

BMP4:

Bone morphogenic protein 4

SDF1:

Stromal cell-derived factor 1

VEGF:

Vascular endothelial growth factor

SNK:

Student-Newman-Keuls

References

  1. McGinley LM, Sims E, Lunn JS, Kashlan ON, Chen KS, Bruno ES, Pacut CM, Hazel T, Johe K, Sakowski SA, Feldman EL (2016) Human cortical neural stem cells expressing insulin-like growth factor-I: a novel cellular therapy for Alzheimer’s disease. Stem Cells Transl Med 5(3):379–391. doi:10.5966/sctm.2015-0103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Toda H, Takahashi J, Iwakami N, Kimura T, Hoki S, Mozumi-Kitamura K, Ono S, Hashimoto N (2001) Grafting neural stem cells improved the impaired spatial recognition in ischemic rats. Neurosci Lett 316(1):9–12

    Article  CAS  PubMed  Google Scholar 

  3. Mercier F (2016) Fractones: extracellular matrix niche controlling stem cell fate and growth factor activity in the brain in health and disease. Cell Mol Life Sci

  4. Zhou J, Peng W, Xu M, Li W, Liu Z (2015) The effectiveness and safety of acupuncture for patients with Alzheimer disease: a systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 94(22):e933. doi:10.1097/MD.0000000000000933

    Article  CAS  Google Scholar 

  5. Takeda T, Hosokawa M, Takeshita S, Irino M, Higuchi K, Matsushita T, Tomita Y, Yasuhira K, Hamamoto H, Shimizu K, Ishii M, Yamamuro T (1981) A new murine model of accelerated senescence. Mech Ageing Dev 17(2):183–194. doi:10.1016/0047-6374(81)90084-1

    Article  CAS  PubMed  Google Scholar 

  6. Porquet D, Andrés-Benito P, Griñán-Ferré C, Camins A, Ferrer I, Canudas AM, Del Valle J, Pallàs M (2015) Amyloid and tau pathology of familial Alzheimer’s disease APP/PS1 mouse model in a senescence phenotype background (SAMP8). Age (Dordr) 37(1):12. doi:10.1007/s11357-015-9747-3

    Article  Google Scholar 

  7. Dobarro M, Orejana L, Aguirre N, Ramírez MJ (2013) Propranolol restores cognitive deficits and improves amyloid and tau pathologies in a senescence-accelerated mouse model. Neuropharmacology 64:137–144. doi:10.1016/j.neuropharm.2012.06.047

    Article  CAS  PubMed  Google Scholar 

  8. Cheng H, Yu J, Jiang Z, Zhang X, Liu C, Peng Y, Chen F, Qu Y, Jia Y, Tian Q, Xiao C, Chu Q, Nie K, Kan B, Hu X, Han J (2008) Acupuncture improves cognitive deficits and regulates the brain cell proliferation of SAMP8 mice. Neurosci Lett 432(2):111–116. doi:10.1016/j.neulet.2007.12. 009

    Article  CAS  PubMed  Google Scholar 

  9. Zhao L, Jia Y, Yan D, Zhou C, Han J, Yu J (2013) Aging-related changes of triose phosphate isomerase of senescence accelerated mouse with aging and effects of acupuncture intervention. Neurosci Lett 542:59–64. doi:10.1016/j.neulet.2013.03.002

    Article  CAS  PubMed  Google Scholar 

  10. Li G, Zhang X, Cheng H, Shang X, Xie H, Zhang X, Yu J, Han J (2012) Acupuncture improves cognitive deficits and increases neuron density of the hippocampus in middle-aged SAMP8 mice. Acupunct Med 30(4):339–345. doi:10.1136/acupmed-2012-010180

    Article  PubMed  Google Scholar 

  11. Belenguer G, Domingo-Muelas A, Ferrón SR, Morante-Redolat JM, Fariñas I (2016) Isolation, culture and analysis of adult subependymal neural stem cells. Differentiation 91(4–5):28–41. doi:10.1016/j.diff.2016.01.005

    Article  CAS  PubMed  Google Scholar 

  12. Carreira BP, Morte MI, Santos AI, Lourenço AS, Ambrósio AF, Carvalho CM, Araújo IM (2014) Nitric oxide from inflammatory origin impairs neural stem cell proliferation by inhibiting epidermal growth factor receptor signaling. Front Cell Neurosci 8:343. doi:10.3389/fncel.2014.00343

    Article  PubMed  PubMed Central  Google Scholar 

  13. Zhang S, Xie R, Zhao T, Yang X, Han L, Ye F, Lei T, Wan F (2014) Neural stem cells preferentially migrate to glioma stem cells and reduce their stemness phenotypes. Int J Oncol 45(5):1989–1996. doi:10.3892/ijo.2014.2629

    CAS  PubMed  Google Scholar 

  14. Wu CC, Lien CC, Hou WH, Chiang PM, Tsai KJ (2016) Gain of BDNF function in engrafted neural stem cells promotes the therapeutic potential for Alzheimer’s disease. Sci Rep 6:27358. doi:10.1038/srep27358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Joppé SE, Hamilton LK, Cochard LM, Levros LC, Aumont A, Barnabé-Heider F, Fernandes KJ (2015) Bone morphogenetic protein dominantly suppresses epidermal growth factor-induced proliferative expansion of adult forebrain neural precursors. Front Neurosci 9:407. doi:10.3389/fnins.2015.00407

    Article  PubMed  PubMed Central  Google Scholar 

  16. Cui C, Wang P, Cui N, Song S, Liang H, Ji A (2016) Sulfated polysaccharide isolated from the sea cucumber Stichopus japonicas promotes the SDF-1α/CXCR4 axis-induced NSC migration via the PI3K/Akt/FOXO3a, ERK/MAPK, and NF-κB signaling pathways. Neurosci Lett 616:57–64. doi:10.1016/j.neulet.2016.01.041

    Article  CAS  PubMed  Google Scholar 

  17. Lee HL, Lee HY, Yun Y, Oh J, Che L, Lee M, Ha Y (2016) Hypoxia-specific, VEGF-expressing neural stem cell therapy for safe and effective treatment of neuropathic pain. J Control Release 226:21–34. doi:10.1016/j.jconrel.2016.01.047

    Article  CAS  PubMed  Google Scholar 

  18. Noguchi H, Murao N, Kimura A, Matsuda T, Namihira M, Nakashima K (2016) DNA methyltransferase 1 is indispensable for development of the hippocampal dentate gyrus. J Neurosci 36(22):6050–6068. doi:10.1523/JNEUROSCI.0512-16.2016

    Article  CAS  PubMed  Google Scholar 

  19. Shetty AK, Hattiangady B (2016) Grafted subventricular zone neural stem cells display robust engraftment and similar differentiation properties and form new neurogenic niches in the young and aged hippocampus. Stem Cells Transl Med

  20. Moodley K, Minati L, Contarino V, Prioni S, Wood R, Cooper R, D’Incerti L, Tagliavini F, Chan D (2015) Diagnostic differentiation of mild cognitive impairment due to Alzheimer’s disease using a hippocampus-dependent test of spatial memory. Hippocampus 25(8):939–951. doi:10.1002/hipo.22417

    Article  PubMed  Google Scholar 

  21. Zhang W, Wang GM, Wang PJ, Zhang Q, Sha SH (2014) Effects of neural stem cells on synaptic proteins and memory in a mouse model of Alzheimer’s disease. J Neurosci Res 92(2):185–194. doi:10.1002/jnr.23299

    Article  CAS  PubMed  Google Scholar 

  22. Yan Y, Ma T, Gong K, Ao Q, Zhang X, Gong Y (2014) Adipose-derived mesenchymal stem cell transplantation promotes adult neurogenesis in the brains of Alzheimer’s disease mice. Neural Regen Res 9(8):798–805. doi:10.4103/1673-5374.131596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang C, Chen J, Feng C, Shao X, Liu Q, Zhang Q, Pang Z, Jiang X (2014) Intranasal nanoparticles of basic fibroblast growth factor for brain delivery to treat Alzheimer’s disease. Int J Pharm 461(1–2):192–202. doi:10.1016/j.ijpharm.2013.11.049

    Article  CAS  PubMed  Google Scholar 

  24. Kumano G, Smith WC (2000) FGF signaling restricts the primary blood islands to ventral mesoderm. Dev Biol 228(2):304–314

    Article  CAS  PubMed  Google Scholar 

  25. Bae DK, Park D, Lee SH, Yang G, Kyung J, Kim D, Shin K, Choi EK, Kim G, Hong JT, Kim SU, Kim YB (2016) Comparative effects of human neural stem cells and oligodendrocyte progenitor cells on the neurobehavioral disorders of experimental autoimmune encephalomyelitis mice. Stem Cells Int 2016:4079863. doi:10.1155/2016/4079863

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was funded by National Natural Science Foundation of China (81202740), Specialized Research Fund for the Doctoral Program of Higher Education (20121210120002), Tianjin Natural Science Fund (12JCQNJC07400), State-funded Construction Projects-Key Specialized Subject of Clinical Laboratory Medicine (2013-544), and Tianjin Public Health Bureau Science and Technology Fund (2014KY15, 2013KG142).

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Authors and Affiliations

  1. First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Lan Zhao, Li Li, Huiyan Shi, Bohong Kan, Zhen Li, Jingxian Han & Jianchun Yu

  2. Tianjin Key Laboratory of Acupuncture and Moxibustion, Tianjin, 300193, China

    Lan Zhao, Li Li, Huiyan Shi, Bohong Kan & Zhen Li

  3. Tianjin First Center Hospital, Tianjin, 300192, China

    Chunlei Zhou

  4. Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China

    Jianwei Liu & Yunzhu Li

Authors
  1. Lan Zhao
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  2. Chunlei Zhou
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  3. Li Li
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  4. Jianwei Liu
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  5. Huiyan Shi
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  10. Jianchun Yu
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Correspondence to Lan Zhao or Jianchun Yu.

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The authors declare that they have no conflict of interest.

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Lan Zhao and Chunlei Zhou contributed equally to this work.

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Zhao, L., Zhou, C., Li, L. et al. Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer’s Disease Treated with Hippocampal Neural Stem Cells. Mol Neurobiol 54, 5120–5130 (2017). https://doi.org/10.1007/s12035-016-0054-5

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  • DOI: https://doi.org/10.1007/s12035-016-0054-5

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