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RhoC Involved in the Migration of Neural Stem/Progenitor Cells

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Abstract

Alzheimer’s disease (AD) is characterized by deposition of beta-amyloid peptides (Aβ) and progressive loss of neurons. Neural stem/progenitor cells (NSPCs) can proliferate and produce immature neurons even in the brain of AD patients. However, Aβ42 significantly decreased the expression of RhoC in NSPCs during the co-incubation (P < 0.01). Treating with RhoC siRNA prevented membrane from protrusion and led to a significant reduction in cell migration in responses to SDF-1. Compared with wild-type mice, the numbers of RhoC-immunoreactive cells in hippocampus and cortex were significantly down-regulated in APP/PS1 mice aged 9 months. The results suggest that Aβ42 down-regulates the expression of RhoC in NSPCs in vitro and in vivo; down-regulated RhoC expression results in decreased migration of NSPCs.

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References

  • Artegiani B, Calegari F (2012) Age-related cognitive decline: can neural stem cells help us? Aging (Albany NY) 4(3):176

    Google Scholar 

  • Chen Z, Jalabi W, Shpargel KB, Farabaugh KT, Dutta R, Yin X, Kidd GJ, Bergmann CC, Stohlman SA, Trapp BD (2012) Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4. J Neurosci 32(34):11706–11715

    Article  CAS  PubMed  Google Scholar 

  • Feng Z, Zhao G, Yu L (2009) Neural stem cells and Alzheimer’s disease: challenges and hope. Am J Alzheimer’s Dis Other Dementias 24(1):52–57

    Article  Google Scholar 

  • Gengler S, McClean PL, McCurtin R, Gault VA, Hölscher C (2010) Val (8) GLP-1 rescues synaptic plasticity and reduces dense core plaques in APP/PS1 mice. Neurobiol of Aging 33(2):265–276

    Article  Google Scholar 

  • Grienberger C, Rochefort NL, Adelsberger H, Henning HA, Hill DN, Reichwald J, Staufenbiel M, Konnerth A (2012) Staged decline of neuronal function in vivo in an animal model of Alzheimer’s disease. Nat Commun 3:774

    Article  PubMed Central  PubMed  Google Scholar 

  • Han J, Li L, Hu J, Yu L, Zheng Y, Guo J, Zheng X, Yi P, Zhou Y (2010) Epidermal growth factor stimulates human trophoblast cell migration through Rho A and Rho C activation. Endocrinology 151(4):1732–1742

    Article  CAS  PubMed  Google Scholar 

  • Iiizumi M, Bandyopadhyay S, Pai SK, Watabe M, Hirota S, Hosobe S, Tsukada T, Miura K, Saito K, Furuta E (2008) RhoC promotes metastasis via activation of the Pyk2 pathway in prostate cancer. Cancer Res 68(18):7613–7620

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ikoma T, Takahashi T, Nagano S, Li Y-M, Ohno Y, Ando K, Fujiwara T, Fujiwara H, Kosai K-i (2004) A definitive role of RhoC in metastasis of orthotopic lung cancer in mice. Clin Cancer Res 10(3):1192–1200

    Article  CAS  PubMed  Google Scholar 

  • Karuppagounder SS, Xu H, Shi Q, Chen LH, Pedrini S, Pechman D, Baker H, Beal MF, Gandy SE, Gibson GE (2009) Thiamine deficiency induces oxidative stress and exacerbates the plaque pathology in Alzheimer’s mouse model. Neurobiol Aging 30(10):1587–1600

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kim H, Cooke MJ, Shoichet MS (2012) Creating permissive microenvironments for stem cell transplantation into the central nervous system. Trends Biotechnol 30(1):55–63

    Article  CAS  PubMed  Google Scholar 

  • Kimiwada T, Sakurai M, Ohashi H, Aoki S, Tominaga T, Wada K (2009) Clock genes regulate neurogenic transcription factors, including NeuroD1, and the neuronal differentiation of adult neural stem/progenitor cells. Neurochem Int 54(5):277–285

    Article  CAS  PubMed  Google Scholar 

  • Kimura A, Ohmori T, Ohkawa R, Madoiwa S, Mimuro J, Murakami T, Kobayashi E, Hoshino Y, Yatomi Y, Sakata Y (2006) Essential roles of sphingosine 1-phosphate/S1P1 receptor axis in the migration of neural stem cells toward a site of spinal cord injury. Stem Cells 25(1):115–124

    Article  PubMed  Google Scholar 

  • Kitzing T, Wang Y, Pertz O, Copeland J, Grosse R (2010) Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC. Oncogene 29(16):2441–2448

    Article  CAS  PubMed  Google Scholar 

  • Kondo T, Sentani K, Oue N, Yoshida K, Nakayama H, Yasui W (2003) Expression of Rhoc is associated with metastasis of gastric carcinomas. Pathobiology 71(1):19–25

    Article  CAS  Google Scholar 

  • Lee DA, Blackshaw S (2012) Functional implications of hypothalamic neurogenesis in the adult mammalian brain. Int J Dev Neurosci 30(8):615–621

    Article  PubMed Central  PubMed  Google Scholar 

  • Leong SY, Faux CH, Turbic A, Dixon KJ, Turnley AM (2011) The Rho kinase pathway regulates mouse adult neural precursor cell migration. Stem Cells 29(2):332–343

    Article  CAS  PubMed  Google Scholar 

  • Lovell MA, Geiger H, Van Zant GE, Lynn BC, Markesbery WR (2006) Isolation of neural precursor cells from Alzheimer’s disease and aged control postmortem brain. Neurobiol Aging 27(7):909

    Article  PubMed  Google Scholar 

  • Luo Y, Cai J, Liu Y, Xue H, Chrest FJ, Wersto RP, Rao M (2002) Microarray analysis of selected genes in neural stem and progenitor cells. J Neurochem 83(6):1481–1497

    Article  CAS  PubMed  Google Scholar 

  • Ridley AJ, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70(3):389

    Article  CAS  PubMed  Google Scholar 

  • Russo I, Caracciolo L, Tweedie D, Choi SH, Greig NH, Barlati S, Bosetti F (2012) 3, 6′-Dithiothalidomide, a new TNF-α synthesis inhibitor, attenuates the effect of Aβ1–42 intracerebroventricular injection on hippocampal neurogenesis and memory deficit. J Neurochem 122(6):1181–1192

    Article  CAS  PubMed  Google Scholar 

  • Salhia B, Rutten F, Nakada M, Beaudry C, Berens M, Kwan A, Rutka JT (2005) Inhibition of Rho-kinase affects astrocytoma morphology, motility, and invasion through activation of Rac1. Cancer Res 65(19):8792–8800

    Article  CAS  PubMed  Google Scholar 

  • Shruster A, Eldar-Finkelman H, Melamed E, Offen D (2011) Wnt signaling pathway overcomes the disruption of neuronal differentiation of neural progenitor cells induced by oligomeric amyloid β-peptide. J Neurochem 116(4):522–529

    Article  CAS  PubMed  Google Scholar 

  • Sun J, Sha B, Zhou W, Yang Y (2010) VEGF-mediated angiogenesis stimulates neural stem cell proliferation and differentiation in the premature brain. Biochem Biophys Res Commun 394(1):146–152

    Article  CAS  PubMed  Google Scholar 

  • Theus MH, Ricard J, Bethea JR, Liebl DJ (2010) EphB3 limits the expansion of neural progenitor cells in the subventricular zone by regulating p53 during homeostasis and following traumatic brain injury. Stem Cells 28(7):1231–1242

    CAS  PubMed Central  PubMed  Google Scholar 

  • Turdi S, Guo R, Huff AF, Wolf EM, Culver B, Ren J (2009) Cardiomyocyte contractile dysfunction in the appswe/ps1de9 mouse model of Alzheimer’s disease. PLoS One 4(6):e6033

    Article  PubMed Central  PubMed  Google Scholar 

  • Wang Z, Hao Y, Lowe AW (2008) The adenocarcinoma-associated antigen, AGR2, promotes tumor growth, cell migration, and cellular transformation. Cancer Res 68(2):492–497

    Article  CAS  PubMed  Google Scholar 

  • Wu Y, Chen Y, Sang J, Xu W (2011) RhoC protein stimulates migration of gastric cancer cells through interaction with scaffold protein IQGAP1. Mol Med Rep 4(4):697

    CAS  PubMed  Google Scholar 

  • Yazawa H, Yu ZUXI, Le Y, Gong W, Ferrans VJ, Oppenheim JJ, LI CCHIH, Wang JIM (2001) β amyloid peptide (Aβ42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. FASEB J 15(13):2454–2462

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Wang ZJ, Lok KH, Yin M (2012) Aβ42 induces desensitization of CXCR4 via FPR in neural stem/progenitor cells. Biol Pharm Bull 35(2):131–138

    Article  CAS  PubMed  Google Scholar 

  • Zhao Y, Zong Z, Xu H (2010) RhoC expression level is correlated with the clinicopathological characteristics of ovarian cancer and the expression levels of ROCK-I, VEGF, and MMP9. Gynecol Oncol 116(3):563–571

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Chan CH, Ma Q, Xu X, Xiao Z, Tan EK (2011) The roles of amyloid precursor protein (APP) in neurogenesis: implications to pathogenesis and therapy of Alzheimer disease. Cell Adhesion Migr 5(4):280–292

    Article  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Fund (81270432) and the Polytechnic crossover Foundation of Shanghai Jiao Tong University (AE1700003).

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No conflicts of interest were declared.

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Authors and Affiliations

  1. School of Pharmacy, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai, 200240, China

    Can Zhang, Xuemei Ge, Kenghoe Lok, Lu Zhao, Ming Yin & Ze-Jian Wang

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  1. Can Zhang
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  2. Xuemei Ge
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  3. Kenghoe Lok
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  4. Lu Zhao
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  5. Ming Yin
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  6. Ze-Jian Wang
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Correspondence to Ming Yin or Ze-Jian Wang.

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Zhang, C., Ge, X., Lok, K. et al. RhoC Involved in the Migration of Neural Stem/Progenitor Cells. Cell Mol Neurobiol 34, 409–417 (2014). https://doi.org/10.1007/s10571-014-0026-0

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  • DOI: https://doi.org/10.1007/s10571-014-0026-0

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