Top

Irish Journal of Medical Science (1971 -)

Published in:

01-06-2011 | Original Article

Wnt/beta-catenin is involved in the proliferation of hippocampal neural stem cells induced by hypoxia

Authors: X.-P. Cui, Y. Xing, J.-M. Chen, S.-W. Dong, D.-J. Ying, D. T. Yew

Published in: Irish Journal of Medical Science (1971 -) | Issue 2/2011

Abstract

Background and aim

Beta-catenin, as a major effector molecule in the canonical Wnt signaling pathway, could regulate adult neurogenesis. Here, the role of Wnt/β-catenin signaling pathway in the proliferation of hippocampal neural stem cells (NSCs) induced by hypoxia was investigated.

Methods

The hippocampal NSCs of neonatal green fluorescent protein transgenic mice on day 0 were cultured in hypoxia (5% O₂) and traditional O₂ (20% O₂). The expression of β-catenin, p-GSK-3β, and cyclinD1 in NSCs was measured under hypoxia or traditional O₂ by western blotting. NSCs were electroporated with pTOPFLASH reporter in different conditions and the LEF/TCF-dependent luciferase activity was assayed.

Results

Hypoxia increased the proliferation and reduced the apoptosis of hippocampal NSCs. NSCs proliferation was inhibited by transfecting with pAxin, whereas promoted by transfecting with pβ-catenin.

Conclusion

Hypoxia could enhance the proliferation of hippocampal NSCs and β-catenin contributed to this action.

Reynolds BA, Weiss S (1992) Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science 255:1707–1710PubMedCrossRef

Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438PubMedCrossRef

Ming GL, Song H (2005) Adult neurogenesis in the mammalian central nervous system. Annu Rev Neurosci 28:223–250PubMedCrossRef

Taupin P (2006) The therapeutic potential of adult neural stem cells. Curr Opin Mol Ther 8:225–231PubMed

Alvarez-Buylla A, Lim DA (2004) For the long run: maintaining germinal niches in the adult brain. Neuron 41:683–686PubMedCrossRef

Agrawal S, Schaffer DV (2005) In situ stem cell therapy: novel targets, familiar challenges. Trends Biotechnol 23:78–83PubMedCrossRef

Yang Z, Levison SW (2006) Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone. Neuroscience 139:555–564PubMedCrossRef

Park KI, Hack MA, Ourednik J et al (2006) Acute injury directs the migration, proliferation, and differentiation of solid organ stem cells: evidence from the effect of hypoxia-ischemia in the CNS on clonal “reporter” neural stem cells. Exp Neurol 199:156–178PubMedCrossRef

Felling RJ, Snyder MJ, Romanko MJ et al (2006) Neural stem/progenitor cells participate in the regenerative response to perinatal hypoxia/ischemia. J Neurosci 26:4359–4369PubMedCrossRef

10.

Miller J R (2002) The Wnts. Genome Biol 3 (reviews) 3001.1–3001.15

11.

Lie DC, Colamarino SA, Song HJ et al (2005) Wnt signalling regulates adult hippocampal neurogenesis. Nature 437:1370–1375PubMedCrossRef

12.

Willert K, Nusse R (1998) Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev 8:95–102PubMedCrossRef

13.

Chenn A, Walsh CA (2002) Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science 297:365–369PubMedCrossRef

14.

Zechner D, Fujita Y, Hulsken J et al (2003) Beta-catenin signals regulate cell growth and the balance between progenitor cell expansion and differentiation in the nervous system. Dev Biol 258:406–418PubMedCrossRef

15.

Hirabayashi Y, Itoh Y, Tabata H et al (2004) The Wnt/beta-catenin pathway directs neuronal differentiation of cortical neural precursor cells. Development 13:2791–2801CrossRef

16.

Ciani L, Salinas PC (2005) Wnts in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev Neurosci 6:351–362PubMedCrossRef

17.

Roy NS, Wang S, Jiang L et al (2000) In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus. Nat Med 6:271–277PubMedCrossRef

18.

Shin SY, Kim CG, Jho EH et al (2004) Hydrogen peroxide negatively modulates Wnt signaling through downregulation of beta-catenin. Cancer Lett 212:225–231PubMedCrossRef

19.

Korinek V, Barker N, Morin PJ et al (1997) Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC−/− colon carcinoma. Science 275:1784–1787PubMedCrossRef

20.

Arvidsson A, Collin T, Kirik D et al (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8:963–970PubMedCrossRef

21.

Zhang R, Zhang Z, Wang L et al (2004) Activated neural stem cells contribute to stroke-induced neurogenesis and neuroblast migration toward the infarct boundary in adult rats. J Cereb Blood Flow Metab 24:441–448PubMedCrossRef

22.

Jagasia R, Song H, Gage FH et al (2006) New regulators in adult neurogenesis and their potential role for repair. Trends Mol Med 12:400–405PubMedCrossRef

23.

Ille F, Sommer L (2005) Wnt signaling: multiple functions in neural development. Cell Mol Life Sci 62:1100–1108PubMedCrossRef

24.

Reya T, Duncan AW, Ailles L et al (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414PubMedCrossRef

25.

Muroyama Y, Fujihara M, Ikeya M et al (2002) Wnt signaling plays an essential role in neuronal specification of the dorsal spinal cord. Genes Dev 16:548–553PubMedCrossRef

26.

Muroyama Y, Kondoh H, Takada S (2004) Wnt proteins promote neuronal differentiation in neural stem cell culture. Biochem Biophys Res Commun 313:915–921PubMedCrossRef

27.

Schmitt-Graeff A, Ertelt-Heitzmann V, Allgaier HP et al (2005) Coordinated expression of cyclin D1 and LEF-1/TCF transcription factor is restricted to a subset of hepatocellular carcinoma. Liver Int 25:839–847PubMedCrossRef

Title: Wnt/beta-catenin is involved in the proliferation of hippocampal neural stem cells induced by hypoxia
Authors: X.-P. Cui
Y. Xing
J.-M. Chen
S.-W. Dong
D.-J. Ying
D. T. Yew
Publication date: 01-06-2011
Publisher: Springer-Verlag
Published in: Irish Journal of Medical Science (1971 -) / Issue 2/2011
Print ISSN: 0021-1265
Electronic ISSN: 1863-4362
DOI: https://doi.org/10.1007/s11845-010-0566-3

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background and aim

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 2/2011

Nurse-led rapid access vascular examination clinic triage reduces inappropriate referrals for peripheral arterial disease

Intra-abdominal drain fracture following pancreatic necrosectomy

Ireland’s potential MDR-TB and XDR-TB problem

Sarcoidosis presenting with severe hypocalcaemia

A comparison of antibiotic point prevalence survey data from four Irish regional/general hospitals

Pregnancy in women with Type 1 and Type 2 diabetes in Dublin

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials