Electroacupuncture promotes neural stem cell proliferation and neurogenesis in the dentate gyrus of rats following stroke via upregulation of Notch1 expression

Zhao,Junhong; Sui,Minghong; Lü,Xiao; Jin,Dongmei; Zhuang,Zhiqiang; Yan,Tiebin

doi:10.3892/mmr.2015.4279

Electroacupuncture promotes neural stem cell proliferation and neurogenesis in the dentate gyrus of rats following stroke via upregulation of Notch1 expression

Authors:
- Junhong Zhao
- Minghong Sui
- Xiao Lü
- Dongmei Jin
- Zhiqiang Zhuang
- Tiebin Yan
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Affiliations: Department of Rehabilitation Medicine, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China
Published online on: September 2, 2015 https://doi.org/10.3892/mmr.2015.4279
Pages: 6911-6917

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Abstract

Neural stem cells (NSCs) are important in rehabilitation following stroke. Electroacupuncture (EA) treatment has been observed to promote the recovery of neurological functions subsequent to stroke, however, the effects of EA on the proliferation and differentiation of NSCs and its potential mechanisms remain to be elucidated. In the present study, rats, in which a stroke was induced through middle cerebral artery occlusion (MCAO), were treated with EA or control manipulation for 21 days. The modified Neurological Severity score and Morris water maze tests were used to assess the neurological functions of the rats. Bromodeoxyuridine (BrdU)/glial fibrillary acidic protein (GFAP) or BrdU/neuronal marker (NeuN) double immunofluorescence staining were used to examine the proliferation and differentiation of the NSCs. Reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses were performed to detect the expression levels of Notch1 and Hes1 in the dentate gyrus (DG) of the hippocampus of rats following MCAO. The results demonstrated that EA treatment significantly improved the neurological functional recovery of rats following stroke. A significant increase was observed in the number of BrdU+/GAFP+ and BrdU+/NeuN+ cells in the DG area in the EA‑treated rats compared with that of the control group. RT‑qPCR analysis revealed that EA treatment significantly increased the expression levels of Notch1 and Hes1, which may account for the enhanced proliferation and differentiation of NSCs. In conclusion, to the best of our knowledge, the present study was the first to demonstrate that EA treatment promoted NSC proliferation and neurogenesis in the DG area through the upregulation of Notch signaling following a stroke; therefore, EA may be a useful novel therapeutic strategy in future stroke treatment.

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1	Kavanagh S, Knapp M and Patel A: Costs and disability among stroke patients. J Public Health Med. 21:385–394. 1999. View Article : Google Scholar
2	De Keyser J, Sulter G and Luiten PG: Clinical trials with neuro-protective drugs in acute ischaemic stroke: are we doing the right thing? Trends Neurosci. 22:535–540. 1999. View Article : Google Scholar : PubMed/NCBI
3	Liebeskind DS and Kasner SE: Neuroprotection for ischaemic stroke: an unattainable goal? CNS Drugs. 15:165–174. 2001. View Article : Google Scholar : PubMed/NCBI
4	Gage FH and Temple S: Neural stem cells: generating and regenerating the brain. Neuron. 80:588–601. 2013. View Article : Google Scholar : PubMed/NCBI
5	Zhao C, Deng W and Gage FH: Mechanisms and functional implications of adult neurogenesis. Cell. 132:645–660. 2008. View Article : Google Scholar : PubMed/NCBI
6	Reynolds BA and Weiss S: Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 255:1707–1710. 1992. View Article : Google Scholar : PubMed/NCBI
7	Weiss S, Reynolds BA, Vescovi AL, Morshead C, Craig CG and van der Kooy D: Is there a neural stem cell in the mammalian forebrain? Trends Neurosci. 19:387–393. 1996. View Article : Google Scholar : PubMed/NCBI
8	Reynolds BA and Weiss S: Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol. 175:1–13. 1996. View Article : Google Scholar : PubMed/NCBI
9	McKay R: Stem cells in the central nervous system. Science. 276:66–71. 1997. View Article : Google Scholar : PubMed/NCBI
10	Liu J, Solway K, Messing RO and Sharp FR: Increased neuro-genesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci. 18:7768–7778. 1998.PubMed/NCBI
11	Jin K, Minami M, Lan JQ, et al: Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat. Proc Natl Acad Sci USA. 98:4710–4715. 2001. View Article : Google Scholar : PubMed/NCBI
12	Arvidsson A, Collin T, Kirik D, Kokaia Z and Lindvall O: Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med. 8:963–970. 2002. View Article : Google Scholar : PubMed/NCBI
13	Takasawa K, Kitagawa K, Yagita Y, et al: Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 22:299–307. 2002. View Article : Google Scholar : PubMed/NCBI
14	Ming GL and Song H: Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron. 70:687–702. 2011. View Article : Google Scholar : PubMed/NCBI
15	Lie DC, Song H, Colamarino SA, Ming GL and Gage FH: Neurogenesis in the adult brain: new strategies for central nervous system diseases. Annu Rev Pharmacol Toxicol. 44:399–421. 2004. View Article : Google Scholar : PubMed/NCBI
16	Ceniceros S and Brown GR: Acupuncture: a review of its history, theories and indications. South Med J. 91:1121–1125. 1998. View Article : Google Scholar : PubMed/NCBI
17	Yang R, Huang ZN and Cheng JS: Anticonvulsion effect of acupuncture might be related to the decrease of neuronal and inducible nitric oxide synthases. Acupunct Electrother Res. 24:161–167. 1999. View Article : Google Scholar
18	Junhua Z, Menniti-Ippolito F, Xiumei G, et al: Complex traditional Chinese medicine for poststroke motor dysfunction: a systematic review. Stroke. 40:2797–2804. 2009. View Article : Google Scholar : PubMed/NCBI
19	Ulett GA, Han S and Han JS: Electroacupuncture: mechanisms and clinical application. Biol Psychiatry. 44:129–138. 1998. View Article : Google Scholar : PubMed/NCBI
20	Tong RK, Ng MF and Li LS: Effectiveness of gait training using an electromechanical gait trainer, with and without functional electric stimulation, in subacute stroke: a randomized controlled trial. Arch Phys Med Rehabil. 87:1298–1304. 2006. View Article : Google Scholar : PubMed/NCBI
21	Yan T, Hui-Chan CW and Li LS: Functional electrical stimulation improves motor recovery of the lower extremity and walking ability of subjects with first acute stroke: a randomized placebo-controlled trial. Stroke. 36:80–85. 2005. View Article : Google Scholar
22	Ho TJ, Chan TM, Ho LI, Lai CY, Lin CH, Macdonald I, Harn HJ, Lin JG, Lin SZ and Chen YH: The possible role of stem cells in acupuncture treatment for neurodegenerative diseases: a literature review of basic studies. Cell Transplant. 23:559–566. 2014. View Article : Google Scholar : PubMed/NCBI
23	Ke Z, Yip SP, Li L, Zheng XX and Tong KY: The effects of voluntary, involuntary and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model. PLoS One. 6:e166432011. View Article : Google Scholar
24	Xi GM, Wang HQ, He GH, Huang CF and Wei GY: Evaluation of murine models of permanent focal cerebral ischemia. Chin Med J (Engl). 117:389–394. 2004.
25	Yang Y, Li Q, Miyashita H, Howlett W, Siddiqui M and Shuaib A: Usefulness of postischemic thrombolysis with or without neuroprotection in a focal embolic model of cerebral ischemia. J Neurosurg. 92:841–847. 2000. View Article : Google Scholar : PubMed/NCBI
26	Yang Y, Li Q and Shuaib A: Neuroprotection by 2-h postischemia administration of two free radical scavengers, alpha-phenyl-n-tert-butyl-nitrone (PBN) and N-tert-butyl-(2-sulfophenyl)-nitrone (S-PBN), in rats subjected to focal embolic cerebral ischemia. Exp Neurol. 163:39–45. 2000. View Article : Google Scholar : PubMed/NCBI
27	Chen J, Sanberg PR, Li Y, et al: Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke. 32:2682–2688. 2001. View Article : Google Scholar : PubMed/NCBI
28	Mohapel P, Mundt-Petersen K, Brundin P and Frielingsdorf H: Working memory training decreases hippocampal neurogenesis. Neuroscience. 142:609–613. 2006. View Article : Google Scholar : PubMed/NCBI
29	Chen Y, Pan K, Li S, Xia J, Wang W, Chen J, Zhao J, Lü L, Wang D, Pan Q, et al: Decreased expression of V-set and immunoglobulin domain containing 1 (VSIG1) is associated with poor prognosis in primary gastric cancer. J Surg Oncol. 106:286–293. 2012. View Article : Google Scholar
30	Kim MW, Chung YC, Jung HC, et al: Electroacupuncture enhances motor recovery performance with brain-derived neurotrophic factor expression in rats with cerebral infarction. Acupunct Med. 30:222–226. 2012. View Article : Google Scholar : PubMed/NCBI
31	Gu Y, Janoschka S and Ge S: Neurogenesis and hippocampal plasticity in adult brain. Curr Top Behav Neurosci. 15:31–48. 2013. View Article : Google Scholar
32	Grisolía JS: CNS stem cell transplantation: clinical and ethical perspectives. Brain Res Bull. 57:823–826. 2002. View Article : Google Scholar : PubMed/NCBI
33	Piccin D, Yu F and Morshead CM: Notch signaling imparts and preserves neural stem characteristics in the adult brain. Stem Cells Dev. 22:1541–1550. 2013. View Article : Google Scholar
34	Pujia F, Serrao M, Brienza M, et al: Effects of a selective serotonin reuptake inhibitor escitalopram on the cutaneous silent period: A randomized controlled study in healthy volunteers. Neurosci Lett. 566:17–20. 2014. View Article : Google Scholar : PubMed/NCBI
35	Guo YJ, Zhang ZJ, Wang SH, Sui YX and Sun Y: Notch1 signaling, hippocampal neurogenesis and behavioral responses to chronic unpredicted mild stress in adult ischemic rats. Prog Neuropsychopharmacol Biol Psychiatry. 33:688–694. 2009. View Article : Google Scholar : PubMed/NCBI
36	Chen J, Zacharek A, Li A, et al: Atorvastatin promotes presenilin-1 expression and Notch1 activity and increases neural progenitor cell proliferation after stroke. Stroke. 39:220–226. 2008. View Article : Google Scholar
37	Wang L, Chopp M, Zhang RL, et al: The Notch pathway mediates expansion of a progenitor pool and neuronal differentiation in adult neural progenitor cells after stroke. Neuroscience. 158:1356–1363. 2009. View Article : Google Scholar :