Skip to main content
PMC home page
Neuroscience Bulletin logoLink to Neuroscience Bulletin
. 2011 Dec 3;27(6):413–421. doi: 10.1007/s12264-011-1838-2

Roles of NG2 glial cells in diseases of the central nervous system

NG2 细胞与中枢神经系统疾病

Jian-Ping Xu 1, Jie Zhao 1,✉, Shao Li 1,✉
PMCID: PMC5560387  PMID: 22108818

Abstract

NG2 cells are a novel distinct class of central nervous system (CNS) glial cells, characterized by the expression of the chondroitin sulfate proteoglycan NG2. They have been detected in a variety of human CNS diseases. As morphological, physiological and biomolecular studies of NG2 cells have been conducted, their roles have been gradually revealed. Research on cellular and molecular mechanisms in the pathophysiological state was built on the preliminary findings of their physiological functions; and in turn, this helps to clarify their physiological roles and leads to the identification of novel therapeutic targets. This review summarizes recent findings regarding the potential roles of NG2 cells in traumatic brain injury, multiple sclerosis, glioma, epilepsy, Alzheimer’s disease and electroconvulsive therapy for depression.

Keywords: NG2 cell, electrophysiology, multiple sclerosis, glioma, Alzheimer’s disease, epilepsy

Contributor Information

Jie Zhao, Email: zhaoj@dlmedu.edu.cn.

Shao Li, Phone: +86-411-86110287, Email: lishao89@hotmail.com.

References

  • [1].Nishiyama A., Komitova M., Suzuki R., Zhu X. Polydendrocytes (NG2 cells): multifunctional cells with lineage plasticity. Nat Rev Neurosci. 2009;10(1):9–22. doi: 10.1038/nrn2495. [DOI] [PubMed] [Google Scholar]
  • [2].Levison S.W., Young G.M., Goldman J.E. Cycling cells in the adult rat neocortex preferentially generate oligodendroglia. J Neurosci Res. 1999;57:435–446. [PubMed] [Google Scholar]
  • [3].Olivier C., Cobos I., Perez Villegas E.M., Spassky N., Zalc B., Martinez S., et al. Monofocal origin of telencephalic oligodendrocytes in the anterior entopeduncular area of the chick embryo. Development. 2001;128:1757–1769. doi: 10.1242/dev.128.10.1757. [DOI] [PubMed] [Google Scholar]
  • [4].Nishiyama A., Yu M., Drazba J.A., Tuohy V.K. Normal and reactive NG2+ glial cells are distinct from resting and activated microglia. J Neurosci Res. 1999;48:299–312. doi: 10.1002/(sici)1097-4547(19970515)48:4<299::aid-jnr2>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  • [5].Komitova M., Zhu X., Serwanski D.R., Nishiyama A. NG2 cells are distinct from neurogenic cells in the postnatal mouse subventricular zone. J Comp Neurol. 2009;512(5):702–716. doi: 10.1002/cne.21917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Kitada M., Rowitch D.H. Transcription factor co-expression patterns indicate heterogeneity of oligodendroglial subpopulations in adult spinal cord. Glia. 2006;54:35–46. doi: 10.1002/glia.20354. [DOI] [PubMed] [Google Scholar]
  • [7].Ligon K.L., Kesari S., Kitada M., Sun T., Arnett H.A., Alberta J.A., et al. Development of NG2 neural progenitor cells requires Olig gene function. Proc Natl Acad Sci U S A. 2006;103:7853–7858. doi: 10.1073/pnas.0511001103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Lu Q.R., Sun T., Zhu Z., Ma N., Garcia M., Stiles C.D., et al. Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection. Cell. 2002;109:75–86. doi: 10.1016/s0092-8674(02)00678-5. [DOI] [PubMed] [Google Scholar]
  • [9].Zhou Q., Anderson D.J. The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification. Cell. 2002;109:61–73. doi: 10.1016/s0092-8674(02)00677-3. [DOI] [PubMed] [Google Scholar]
  • [10].Zhu X., Hill R.A., Nishiyama A. NG2 cells generate oligodendrocytes and gray matter astrocytes in the spinal cord. Neuron Glia Biol. 2008;4(1):19–26. doi: 10.1017/S1740925X09000015. [DOI] [PubMed] [Google Scholar]
  • [11].Zhu X., Bergles D.E., Nishiyama A. NG2 cells generate both oligodendrocytes and gray matter astrocytes. Development. 2008;135:145–157. doi: 10.1242/dev.004895. [DOI] [PubMed] [Google Scholar]
  • [12].Windrem M.S., Nunes M.C., Rashbaum W.K., Schwartz T.H., Goodman R.A., McKhann G., 2nd, et al. Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenically dysmyelinated brain. Nature Med. 2004;10:93–97. doi: 10.1038/nm974. [DOI] [PubMed] [Google Scholar]
  • [13].Rivers R.E., Young K.M., Rizzi M., Jamen F., Psachoulia K., Wade A., et al. PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nat Neurosci. 2008;11:1392–1401. doi: 10.1038/nn.2220. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [14].Buffo A., Rite I., Tripathi P., Lepier A., Colak D., Horn A.P., et al. Origin and progeny of reactive gliosis: A source of multipotent cells in the injured brain. Proc Natl Acad Sci U S A. 2008;105(9):3581–3586. doi: 10.1073/pnas.0709002105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [15].Belachew S., Chittajallu R., Aguirre A.A., Yuan X., Kirby M., Anderson S., et al. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol. 2003;161:169–186. doi: 10.1083/jcb.200210110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [16].Nunes M.C., Roy N.S., Keyoung H.M., Goodman R.R., McKhann G., 2nd, Jiang L., et al. Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med. 2003;9:439–447. doi: 10.1038/nm837. [DOI] [PubMed] [Google Scholar]
  • [17].Aguirre A., Gallo V. Postnatal neurogenesis and gliogenesis in the olfactory bulb from NG2-expressing progenitors of the subventricular zone. J Neurosci. 2004;24:10530–10541. doi: 10.1523/JNEUROSCI.3572-04.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Aguirre A.A., Chittajallu R., Belachew S., Gallo V. NG2-expressing cells in the subventricular zone are type C-like cells and contribute to interneuron generation in the postnatal hippocampus. J Cell Biol. 2004;165:575–589. doi: 10.1083/jcb.200311141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Belachew S., Chittajallu R., Aguirre A.A., Yuan X., Kirby M., Anderson S. e. a1. Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons. J Cell Biol. 2003;161(1):169–186. doi: 10.1083/jcb.200210110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Matthias K., Kirchhoff F., Seifert G., Huttmann K., Matyash M., Kettenmann H., et al. Segregated expression of AMPA-type glutamate receptors and glutamate transporters defines distinct astrocyte populations in the mouse hippocampus. J Neurosci. 2003;23:1750–1758. doi: 10.1523/JNEUROSCI.23-05-01750.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Zhou M., Kimelberg H.K. Freshly isolated hippocampal CA1 astrocytes comprise two populations differing in glutamate transporter and AMPA receptor expression. J Neurosci. 2001;21(20):7901–7908. doi: 10.1523/JNEUROSCI.21-20-07901.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Bergles D.E., Roberts J.D., Somogyi P., Jahr C.E. Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature. 2000;405(6783):187–191. doi: 10.1038/35012083. [DOI] [PubMed] [Google Scholar]
  • [23].Ge W.P., Yang X.J., Zhang Z., Wang H.K., Shen W., Deng Q.D., et al. Long-term potentiation of neuron-glia synapses mediated by Ca2+-permeable AMPA receptors. Science. 2006;312:1533–1537. doi: 10.1126/science.1124669. [DOI] [PubMed] [Google Scholar]
  • [24].Tan A.M., Zhang W., Levine J.M. NG2: a component of the glial scar that inhibits axon growth. J Anat. 2005;207(6):717–725. doi: 10.1111/j.1469-7580.2005.00452.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].Hampton D.W., Rhodes K.E., Zhao C., Franklin R.J., Fawcett J.W. The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury in the brain. Neuroscience. 2004;127(4):813–820. doi: 10.1016/j.neuroscience.2004.05.028. [DOI] [PubMed] [Google Scholar]
  • [26].Matsumoto H., Kumon Y., Watanabe H., Ohnishi T., Shudou M., Chuai M., et al. Accumulation of macrophage-like cells expressing NG2 proteoglycan and Iba1 in ischemic core of rat brain after transient middle cerebral artery occlusion. J Cereb Blood Flow Metab. 2008;28(1):149–163. doi: 10.1038/sj.jcbfm.9600519. [DOI] [PubMed] [Google Scholar]
  • [27].Wang A., He B.P. Characteristics and functions of NG2 cells in normal brain and neuropathology. J Neurol Res. 2009;31(3):144–150. doi: 10.1179/174313209X393555. [DOI] [PubMed] [Google Scholar]
  • [28].Drew L., Sellers, Philip J. Horner Instructive niches: environmental instructions that confound NG2 proteoglycan expression and the fate-restriction of CNS progenitors. J Anat. 2005;207:727–734. doi: 10.1111/j.1469-7580.2005.00480.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [29].Ligon K.L., Kesari S., Kitada M., Sun T., Arnett H.A., Alberta J.A., et al. Development of NG2 neural progenitor cells requires Olig gene function. Proc Natl Acad Sci U S A. 2006;103:7853–7858. doi: 10.1073/pnas.0511001103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [30].de Castro R., Jr, Tajrishi R., Claros J., Stallcup W.B. Differential responses of spinal axons to transection: influence of the NG2 proteoglycan. Exp Neurol. 2005;192:299–309. doi: 10.1016/j.expneurol.2004.11.027. [DOI] [PubMed] [Google Scholar]
  • [31].Bjartmar C., Trapp B.D. Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol. 2001;14:271–278. doi: 10.1097/00019052-200106000-00003. [DOI] [PubMed] [Google Scholar]
  • [32].Edgar J.M., McLaughlin M., Yool D., Zhang S.C., Fowler J.H., Montague P., et al. Oligodendroglial modulation of fast axonal transport in a mouse model of hereditary spastic paraplegia. J Cell Biol. 2004;166:121–131. doi: 10.1083/jcb.200312012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [33].Ferguson B., Matyszak M.K., Esiri M.M., Perry V.H. Axonal damage in acute multiple sclerosis lesions. Brain. 1997;120:393–399. doi: 10.1093/brain/120.3.393. [DOI] [PubMed] [Google Scholar]
  • [34].Griffiths I., Klugmann M., Anderson T., Yool D., Thomson C., Schwab M.H., et al. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science. 1998;280:1610–1613. doi: 10.1126/science.280.5369.1610. [DOI] [PubMed] [Google Scholar]
  • [35].Raine C.S. The Norton Lecture: a review of the oligodendrocyte in the multiple sclerosis lesion. J Neuroimmunol. 1997;77:135–152. doi: 10.1016/s0165-5728(97)00073-8. [DOI] [PubMed] [Google Scholar]
  • [36].Trapp B.D., Peterson J., Ransohoff R.M., Rudick R., Mork S., Bo L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338:278–285. doi: 10.1056/NEJM199801293380502. [DOI] [PubMed] [Google Scholar]
  • [37].Wilson H.C., Scolding N.J., Raine C.S. Co-expression of PDGF alpha receptor and NG2 by oligodendrocyte precursors in human CNS and multiple sclerosis lesions. J Neuroimmunol. 2006;176(1–2):162–173. doi: 10.1016/j.jneuroim.2006.04.014. [DOI] [PubMed] [Google Scholar]
  • [38].Jennings A., Carroll W. Quantification of oligodendrocyte progenitor cells in human and cat optic nerve: implications for endogenous repair in multiple sclerosis. Glia. 2010;58(12):1425–1436. doi: 10.1002/glia.21018. [DOI] [PubMed] [Google Scholar]
  • [39].Trotter J. NG2-positive cells in CNS function and the pathological role of antibodies against NG2 in demyelinating diseases. Neurol Sci. 2005;233(1–2):37–42. doi: 10.1016/j.jns.2005.03.024. [DOI] [PubMed] [Google Scholar]
  • [40].Paintlia A.S., Paintlia M.K., Singh A.K., Singh I. Inhibition of rho family functions by lovastatin promotes myelin repair in ameliorating experimental autoimmune encephalomyelitis. Mol Pharmacol. 2008;73(5):1381–1393. doi: 10.1124/mol.107.044230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [41].Aharoni R., Herschkovitz A., Eilam R., Blumberg-Hazan M., Sela M., Bruck W., et al. Demyelination arrest and remyelination induced by glatiramer acetate treatment of experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2008;105(32):11358–11363. doi: 10.1073/pnas.0804632105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [42].Jiang S.C., Ballerini P., Buccella S., Giuliani P., Jiang C., Huang X.J., et al. Remyelination after chronic spinal cord injury is associated with proliferation of endogenous adult progenitor cells after systemic administration of guanosine. Purinergic Signal. 2008;4(1):61–71. doi: 10.1007/s11302-007-9093-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Kuhlmann T., Remington L., Cognet I., Bourbonniere L., Zehntner S., Guilhot F., et al. Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis. Am J Pathol. 2006;169(2):584–598. doi: 10.2353/ajpath.2006.051086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Zhang J., Zhang Z.G., Morris D., Li Y., Roberts C., Elias S.B., et al. Neurological functional recovery after thymosin beta4 treatment in mice with experimental auto encephalomyelitis. Neuroscience. 2009;164(4):1887–1893. doi: 10.1016/j.neuroscience.2009.09.054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [45].Butzkueven H., Emery B., Cipriani T., Marriott M.P., Kilpatrick T.J. Endogenous leukemia inhibitory factor production limits autoimmune demyelination and oligodendrocyte loss. Glia. 2006;53(7):696–703. doi: 10.1002/glia.20321. [DOI] [PubMed] [Google Scholar]
  • [46].Redwine J.M., Armstrong R.C. In vivo proliferation of oligodendrocyte progenitors expressing PDGF alpha R during early remyelination. J Neurobiol. 1998;37(3):413–428. doi: 10.1002/(sici)1097-4695(19981115)37:3<413::aid-neu7>3.0.co;2-8. [DOI] [PubMed] [Google Scholar]
  • [47].Patel J.R., McCandless E.E., Dorsey D. CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination. Proc Natl Acad Sci U S A. 2010;107(24):11062–11067. doi: 10.1073/pnas.1006301107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Chekenya M., Pilkington G. NG2 precursor cells in neoplasia: functional, histogenesis and therapeutic implications for malignant brain tumours. J Neurocytol. 2002;31:507–521. doi: 10.1023/a:1025795715377. [DOI] [PubMed] [Google Scholar]
  • [49].Bouvier C., Bartloi C., Aguirre-Cruz L., Virard I., Colin C., Fernandez C., et al. Shared oligodendrocyte lineage gene expression in gliomas and oligodendrocyte progenitor cells. J Neurosurg. 2003;99:344–350. doi: 10.3171/jns.2003.99.2.0344. [DOI] [PubMed] [Google Scholar]
  • [50].Ligon K., Alberta J., Kho A., Weiss J., Kwaan M., Nutt C., et al. The oligodendroglial lineage marker Olig2 is universally expressed in diffuse gliomas. J Neuropathol Exp Neurol. 2004;63:499–509. doi: 10.1093/jnen/63.5.499. [DOI] [PubMed] [Google Scholar]
  • [51].Uhrbom L., Hesselager G., Ostman A., Nister M., Westermark B. Dependence of autocrine growth factor stimulation in PDFG-Binduced mouse brain tumor cells. Int J Cancer. 2000;85:398–406. doi: 10.1002/(sici)1097-0215(20000201)85:3<398::aid-ijc17>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
  • [52].Hu X., Holland E. Applications of mouse glioma models in preclinical trials. Mut Res. 2005;576:54–65. doi: 10.1016/j.mrfmmm.2004.08.023. [DOI] [PubMed] [Google Scholar]
  • [53].Dai C., Celestino J., Okada Y., Louis D., Fuller G., Holland E. PDGF autocrine stimulation dedifferentiates cultured astrocytes and induces oligodendrogliomas and oligoastrocytomas from neural progenitors and astrocytes in vivo. Genes Dev. 2006;15:1913–1925. doi: 10.1101/gad.903001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [54].Shih A.H., Holland E.C. Platelet-derived growth factor (PDGF) and glial tumorigenesis. Cancer Lett. 2006;232:139–147. doi: 10.1016/j.canlet.2005.02.002. [DOI] [PubMed] [Google Scholar]
  • [55].Schrappe M., Klier F., Spiro R., Waltz T., Reisfeld R., Gladson C. Correlation of chondroitin sulfate proteoglycan expression on proliferating brain capillary endothelial cells with the malignant phenotype of astroglial cells. Cancer Res. 1991;51:4986–4993. [PubMed] [Google Scholar]
  • [56].Shoshan Y., Nishiyama A., Chang A., Mork S., Barnett G., Cowell J., et al. Expression of oligodendrocyte progenitor cell antigens by gliomas: implications for the histogenesis of brain tumors. Proc Natl Acad Sci U S A. 1999;96:10361–10366. doi: 10.1073/pnas.96.18.10361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [57].Chekenya M., Hjelstuen M., Enger P.O., Thorsen F., Jacob A.L., Probst B., et al. NG2 proteogycan promotes angiogenesis-dependent tumor growth in CNS by sequestering angiostatin. FASEB J. 2002;16:586–588. doi: 10.1096/fj.01-0632fje. [DOI] [PubMed] [Google Scholar]
  • [58].Chekenya M., Enger P., Thorsen F., Tysnes B., Al-Sarraj S., Read T., et al. The glial precursor proteoglycan NG2 is expressed on tumor neovasculature by vascular pericytes in human malignant brain tumours. Neuropathol Appl Neurobiol. 2002;28:367–380. doi: 10.1046/j.1365-2990.2002.00412.x. [DOI] [PubMed] [Google Scholar]
  • [59].Wiranowska M., Ladd S., Smith S., Gottschall P. CD44 adhesion molecule and neuroglial proteoglycan NG2 as invasive markers of glioma. Brain Cell Biol. 2006;35:159–172. doi: 10.1007/s11068-007-9009-0. [DOI] [PubMed] [Google Scholar]
  • [60].Chekenya M., Krakstad C., Svendsen A., Netland I., Staalsen V., Tysnes B., et al. The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene. 2008;27:5182–5194. doi: 10.1038/onc.2008.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [61].Staugaitis S.M., Trapp B.D. NG2-positive glia in the human central nervous system. Neuron Glia Biol. 2009;5(3/4):35–44. doi: 10.1017/S1740925X09990342. [DOI] [PubMed] [Google Scholar]
  • [62].Tillet E., Ruggiero F., Nishiyama A., Stallcup W. The membranespanning proteoglycan NG2 binds to collagens V and VI through the central non-globular domain of its core protein. J Biol Chem. 1997;272:10769–10776. doi: 10.1074/jbc.272.16.10769. [DOI] [PubMed] [Google Scholar]
  • [63].Hagg T., Portera-Cailliau C., Jucker M., Engvall E. Laminins of the adult mammalian CNS: laminin alpha-2 (merosin M-) chain immunoreactivity is associated with neuronal processes. Brain Res. 1997;764:17–27. doi: 10.1016/s0006-8993(97)00419-8. [DOI] [PubMed] [Google Scholar]
  • [64].Buttery P.C., ffrench-Constant C. Laminin-2/integrin interactions enhance myelin membrane formation by oligodendrocytes. Mol Cell Neurosci. 1999;14:199–212. doi: 10.1006/mcne.1999.0781. [DOI] [PubMed] [Google Scholar]
  • [65].Farin A., Suzuki S., Weiker M., Goldman J., Bruce J., Canoll P. Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia. 2006;53:799–808. doi: 10.1002/glia.20334. [DOI] [PubMed] [Google Scholar]
  • [66].Fukushi J., Makagiansar I., Stallcup W. NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and α3β1 integrin. Mol Biol Cell. 2004;15:3580–3590. doi: 10.1091/mbc.E04-03-0236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [67].Eisenmann K.M., McCarthy J.B., Simpson M.A., Keely P.J., Guan J.L., Tachibana K., et al. Melanoma chondroitin sulphate proteoglycan regulates cell spreading through Cdc42, Ack-1 and p130cas. Nat Cell Biol. 1999;1:507–513. doi: 10.1038/70302. [DOI] [PubMed] [Google Scholar]
  • [68].Yang J., Price M., Neudauer C., Wilson C., Ferrone S., Xia H., et al. Melanoma chondroitin sulfate proteoglycan enhances FAK and ERK activation by distinct mechanisms. J Cell Biol. 2004;165:881–891. doi: 10.1083/jcb.200403174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [69].Makagiansar I.T., Williams S., Dahlin-Huppe K., Fukushi J., Mustelin T., Stallcup W.B. Phosphorylation of NG2 proteoglycan by protein kinase C-α regulates polarized membrane distribution and cell motility. J Biol Chem. 2004;279:55262–55270. doi: 10.1074/jbc.M411045200. [DOI] [PubMed] [Google Scholar]
  • [70].Makagiansar I.T., Williams S., Mustelin T., Stallcup W.B. Differential phosphorylation of NG2 proteoglycan by ERK and PKCα helps balance cell proliferation and migration. J Cell Biol. 2007;178:155–165. doi: 10.1083/jcb.200612084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [71].Goretzki L., Burg M.A., Grako K.A., Stallcup W.B. High affinity binding of bFGF and PDGF-AA to the core protein of the NG2 proteoglycan. J Biol Chem. 1999;274:16831–16837. doi: 10.1074/jbc.274.24.16831. [DOI] [PubMed] [Google Scholar]
  • [72].Burg M.B., Tillet E., Timpl R., Stallcup W.B. Binding of the NG2 proteoglycan to type VI collagen and other extracellular matrix ligands. J Biol Chem. 1996;271:26110–26116. doi: 10.1074/jbc.271.42.26110. [DOI] [PubMed] [Google Scholar]
  • [73].Makagiansar I.T., Williams S., Mustelin T., Stallcup W.B. Differential phosphorylation of NG2 proteoglycan by ERK and PKCα helps balance cell proliferation and migration. J Cell Biol. 2007;178:155–165. doi: 10.1083/jcb.200612084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [74].Joy A.M., Beaudry C.E., Tran N.L., Ponce F.A., Holz D., Demuth T., et al. Migrating glioma cells activate the PI3K pathway and display decreased susceptibility to apoptosis. J Cell Sci. 2003;116:4409–4417. doi: 10.1242/jcs.00712. [DOI] [PubMed] [Google Scholar]
  • [75].Chekenya M., Krakstad C., Svendsen A., Netland I., Staalsen V., Tysnes B., et al. The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene. 2008;27:5182–5194. doi: 10.1038/onc.2008.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [76].Moon R.T., Kohn A.D., De Ferrari G.V., Kaykas A. WNT and beta catenin signalling: diseases and therapies. Nat Rev Genet. 2004;5:691–701. doi: 10.1038/nrg1427. [DOI] [PubMed] [Google Scholar]
  • [77].Salins P., Shawesh S., He Y., Dibrov A., Kashour T., Arthur G., et al. Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling. Neurosci Lett. 2007;412:211–216. doi: 10.1016/j.neulet.2006.07.045. [DOI] [PubMed] [Google Scholar]
  • [78].De Ferrari G.V., Chaco’n M.A., Barría M.I., Garrido J.L., Godoy J.A., Olivares G., et al. Activation of Wnt signaling rescues neurodegeneration and behavioral impairments induced by betaamyloid fibrils. Mol Psychiatry. 2003;8:195–208. doi: 10.1038/sj.mp.4001208. [DOI] [PubMed] [Google Scholar]
  • [79].Alvarez A.R., Godoy J.A., Mullendorff K., Olivares G.H., Bronfman M., Inestrosa N.C. Wnt-3a overcomes beta-amyloid toxicity in rat hippocampal neurons. Exp Cell Res. 2004;297:186–196. doi: 10.1016/j.yexcr.2004.02.028. [DOI] [PubMed] [Google Scholar]
  • [80].Lie D.C., Colamarino S.A., Song H.J., Désiré L., Mira H., Consiglio A., et al. Wnt signalling regulates adult hippocampal neurogenesis. Nature. 2005;437:1370–1375. doi: 10.1038/nature04108. [DOI] [PubMed] [Google Scholar]
  • [81].Teo J.L., Ma H., Nguyen C., Lam C., Kahn M. Specific inhibition of CBP/beta-catenin interaction rescues defects in neuronal differentiation caused by a presenilin-1 mutation. Proc Natl Acad Sci U S A. 2005;102:12171–12176. doi: 10.1073/pnas.0504600102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [82].Behrens J., von Kries J.P., Bruhn L., Wedlich D., Grosschedl R., Birchmeier W., et al. Functional interaction of beta-catenin with the transcription factor LEF-1. Nature. 1996;382:638–642. doi: 10.1038/382638a0. [DOI] [PubMed] [Google Scholar]
  • [83].Nusse R. WNT targets. Repression and activation. Trends Genet. 1999;15:1–3. doi: 10.1016/s0168-9525(98)01634-5. [DOI] [PubMed] [Google Scholar]
  • [84].Brantjes H., Roose J., van De Wetering M., Clevers H. All Tcf HMG box transcription factors interact with Groucho-related corepressors. Nucleic Acids Res. 2001;29:1410–1419. doi: 10.1093/nar/29.7.1410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [85].He P., Shen Y. Interruption of β-catenin signaling reduces neurogenesis in Alzheimer’s disease. J Neurosci. 2009;29(20):6545–6557. doi: 10.1523/JNEUROSCI.0421-09.2009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [86].Garrido J.L., Godoy J.A., Alvarez A., Bronfman M., Inestrosa N.C. Protein kinase C inhibits amyloid beta peptide neurotoxicity by acting on members of the Wnt pathway. FASEB J. 2002;16:1982–1984. doi: 10.1096/fj.02-0327fje. [DOI] [PubMed] [Google Scholar]
  • [87].Salins P., Shawesh S., He Y., Dibrov A., Kashour T., Arthur G., et al. Lovastatin protects human neurons against Abeta-induced toxicity and causes activation of beta-catenin-TCF/LEF signaling. Neurosci Lett. 2007;412:211–216. doi: 10.1016/j.neulet.2006.07.045. [DOI] [PubMed] [Google Scholar]
  • [88].Castelo-Branco G., Rawal N., Arenas E. GSK-3beta inhibition/beta-catenin stabilization in ventral midbrain precursors increases differentiation into dopamine neurons. J Cell Sci. 2004;117:5731–5737. doi: 10.1242/jcs.01505. [DOI] [PubMed] [Google Scholar]
  • [89].Hattiangady B., Shetty A.K. Decreased neuronal differentiation of newly generated cells underlies reduced hippocampal neurogenesis in chronic temporal lobe epilepsy. Hippocampus. 2010;20(1):97–112. doi: 10.1002/hipo.20594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [90].Brilli E., Scali M., Casarosa S., Kohler M., Bozzi Y. Seizures increase importin-beta1 expression in NG2+ cells in the rat hippocampus. J Neurosci Res. 2009;87(3):636–643. doi: 10.1002/jnr.21879. [DOI] [PubMed] [Google Scholar]
  • [91].During M.J., Spencer D.D. Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet. 1993;341:1607–1610. doi: 10.1016/0140-6736(93)90754-5. [DOI] [PubMed] [Google Scholar]
  • [92].Seifert G., Huttmann K., Schramm J., Steinhauser C. Enhanced relative expression of glutamate receptor 1 flip AMPA receptor subunits in hippocampal astrocytes of epilepsy patients with Ammon’s horn sclerosis. J Neurosci. 2004;24:1996–2003. doi: 10.1523/JNEUROSCI.3904-03.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [93].Seifert G., Schroder W., Hinterkeuser S., Schumacher T., Schramm J., Steinhäuser C. Changes in flip/flop splicing of astroglial AMPA receptors in human temporal lobe epilepsy. Epilepsia. 2002;43(Suppl5):162–167. doi: 10.1046/j.1528-1157.43.s.5.10.x. [DOI] [PubMed] [Google Scholar]
  • [94].Schroder W., Seifert G., Hüttmann K., Hinterkeuser S., Steinhäuser C. AMPA receptor-mediated modulation of inward rectifier K+ channels in astrocytes of mouse hippocampus. Mol Cell Neurosci. 2002;19:447–458. doi: 10.1006/mcne.2001.1080. [DOI] [PubMed] [Google Scholar]
  • [95].Jabs R., Pivneva T., Hüttmann K., Wyczynski A., Nolte C., Kettenmann H., et al. Synaptic transmission onto hippocampal glial cells with hGFAP promoter activity. J Cell Sci. 2005;118(Part16):3791–3803. doi: 10.1242/jcs.02515. [DOI] [PubMed] [Google Scholar]
  • [96].Lin S.C., Bergles D.E. Synaptic signaling between GABAergic interneurons and oligodendrocyte precursor cells in the hippocampus. Nat Neurosci. 2004;7(1):24–32. doi: 10.1038/nn1162. [DOI] [PubMed] [Google Scholar]
  • [97].Madesen T.M., Treschow A., Bengzon J., Bolwig T.G., Lindvall O., Tingstrom A. Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry. 2000;47:1043–1049. doi: 10.1016/s0006-3223(00)00228-6. [DOI] [PubMed] [Google Scholar]
  • [98].Jansson L., Wennström M., Johanson A., Tingström A. Glial cell activation in response to electroconvulsive seizures. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(7):1119–1128. doi: 10.1016/j.pnpbp.2009.06.007. [DOI] [PubMed] [Google Scholar]
  • [99].Wennström M., Hellsten J., Ekstrand J., Lindgren H., Tingström A. Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures. Biol Psychiatry. 2006;59(2):178–186. doi: 10.1016/j.biopsych.2005.08.032. [DOI] [PubMed] [Google Scholar]
  • [100].Bolwig T.G., Madsen T.M. Electroconvulsive therapy in melancholia: the role of hippocampal neurogenesis. Acta Psychiatr Scand Suppl. 2007;433:130–135. doi: 10.1111/j.1600-0447.2007.00971.x. [DOI] [PubMed] [Google Scholar]
  • [101].Hellsten J., Wennström M., Mohapel P., Ekdahl C.T., Bengzon J., Tingstrom A. Electroconvulsive seizures increase hippocampal neurogenesis after chronic corticosterone treatment. Eur J Neurosci. 2002;16:283–290. doi: 10.1046/j.1460-9568.2002.02093.x. [DOI] [PubMed] [Google Scholar]

Articles from Neuroscience Bulletin are provided here courtesy of Springer

RESOURCES