Journal of Molecular Histology

, Volume 35, Issue 8–9, pp 749–758 | Cite as

p75 NTR -Immunoreactivity in the subventricular zone of adult male rats: Expression by cycling cells

  • A. Giuliani
  • G. D’Intino
  • M. Paradisi
  • L. Giardino
  • L. Calzà


While the study of in vitro regulation of neural stem cell lineage from both embryonic and adult neurospheres is greatly advanced, much less is known about factors acting in situ for neural stem cell lineage in adult brain. We reported that neurotrophin low affinity receptor p75 NTR is present in the subventricular zone (SVZ) in adult male rats. We then characterized co-distribution of markers associated with precursor cells (nestin and PSA-NCAM) with growth factor receptors (p75 NTR , trkA, EGFr) and proliferation-associated antigens (Ki67 and BrDU-uptake) in adult male rat by immunocytochemistry and confocal laser scan microscopy. Distribution of p75 NTR -immunoreactivity (IR) was investigated using different mono- and polyclonal antisera. p75NTR is not co-distributed with glial fibrillary acid protein. It was found to be co-distributed with a small number of nestin-IR cells, whereas no coexistence with PSA-NCAM-IR was observed. Conversely, p75 NTR -IR was present in numerous dividing cells (Ki-67-positive) and co-distributed with EGFr. In order to verify the possible association between p75 NTR and cell death, we investigated co-distribution of p75 NTR -IR with nuclear condensation images as visualized by Hoechst 33258 staining. While few images indicating nuclear condensation were observed in the SVZ, no coexistence with p75 NTR was found. TrkA- and trkB-IR was not found in the SVZ. We also investigated p75 NTR immunostaining on post-natal day 1 and day 16, because of the dramatic reduction of proliferating cells in SVZ over this time-interval. p75 NTR -IR was not increased in the early post-natal phase. Thus, p75 NTR seems to be associated with cell cycle regulation in SVZ in adult rat brain.


Glial Fibrillary Acid Protein Cell Cycle Regulation Adult Brain Cycling Cell Affinity Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alonso, G 1999Neuronal progenitor-like cells expressing polysialylated neural cell adhesion molecule are present on the ventricular surface of the adult rat brain and spinal cordJ Comp Neurol414149166Google Scholar
  2. Alvarez-Buylla, A, Garcia-Verdugo, JM 2002Neurogenesis in adult subventricular zoneJ Neurosci22629634Google Scholar
  3. Alvarez-Buylla, A, Lois, C 1995Neuronal stem cells in the brain of adult vertebratesStem Cells13263272Google Scholar
  4. Barker, PA, Hussain, NK, McPherson, PS 2002Retrograde signaling by the neurotrophins follows a well-worn trkTrends Neurosci25379381Google Scholar
  5. Barnabé-Heider, F, Miller, FD 2003Endogenously produced neurotrophins regulate survival and differentiation of cortical progenitors via distinct signaling pathwaysJ Neurosci2351495160Google Scholar
  6. Bartlett, WP, Li, XS, Williams, M 1992Expression of IGF-1 mRNA in the murine subventricular zone during postnatal developmentMol Brain Res.12285291Google Scholar
  7. Benzel, I, Barde, YA, Casademunt, E 2001Strain-specific complementation between NRIF1 and NRIF2, two zinc finger proteins sharing structural and biochemical propertiesGene2811930Google Scholar
  8. Bonfanti, L, Peretto, P, Merighi, A, Fasolo, A 1997Newly-generated cells from the rostral migratory stream in the accessory olfactory bulb of the adult ratNeurosci81489502Google Scholar
  9. Calver, AR, Hall, AC, Yu, WP, Walsh, FS, Heath, JK, Betsholtz, C, Richardson, WD 1998Oligodendrocyte population dynamics and the role of PDGF in vivoNeuron20869882Google Scholar
  10. Calza, L, Giardino, L, Pozza, M, Bettelli, C, Micera, A, Aloe, L 1998Proliferation and phenotype regulation in the subventricular zone during experimental allergic encephalomyelitis: in vivo evidence of a role for nerve growth factorProc Natl Acad Sci USA9532093214Google Scholar
  11. Calza, L, Fernandez, M, Giuliani, A, Aloe, L, Giardino, L 2002Thyroid hormone activates oligodendrocyte precursors and increases a myelin-forming protein and NGF content in the spinal cord during experimental allergic encephalomyelitisProc Natl Acad Sci USA9932583263Google Scholar
  12. Calza, L, Giuliani, A, Fernandez, M, Pirondi, S, D’Intino, G, Aloe, L, Giardino, L 2003Neural stem cells and cholinergic neurons: regulation by immunolesion and treatment with mitogens, retinoic acid, and nerve growth factorProc Natl Acad Sci USA10073257330Google Scholar
  13. Cameron, HA, McKay, RD 2001Adult neurogenesis produces a large pool of new granule cells in the dentate gyrusJ Comp Neurol435406417Google Scholar
  14. Casademunt, E, Carter, BD, Benzel, I, Frade, JM, Dechant, G, Barde, YA 1999The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell deathEMBO J1860506061Google Scholar
  15. Cattaneo, E, McKay, R 1990Proliferation and differentiation of neuronal stem cells regulated by nerve growth factorNature347762765Google Scholar
  16. Cheng, A, Wang, S, Cai, J, Rao, MS, Mattson, MP 2003Nitric oxide acts in a positive feedback loop with BDNF to regulate neural progenitor cell proliferation and differentiation in the mammalian brainDev Biol258319333Google Scholar
  17. Chittka, A, Chao, MV 1999Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factorProc Natl Acad Sci USA961070510710Google Scholar
  18. Cortazzo, MH, Kassis, ES, Sproul, KA, Schor, NF 1996Nerve growth factor (NGF)-mediated protection of neural crest cells from antimitotic agent-induced apoptosis: the role of the low-affinity NGF receptorJ Neurosci1638953899Google Scholar
  19. Doetsch, F, Alvarez-Buylla, A 1996Network of tangential pathways for neuronal migration in adult mammalian brainProc Natl Acad Sci USA931489514900Google Scholar
  20. Doetsch, F, Garcia-Verdugo, JM, Alvarez-Buylla, A 1997Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brainJ Neurosci1750465061Google Scholar
  21. Doetsch, F, Garcia-Verdugo, JM, Alvarez-Buylla, A 1999Regeneration of a germinal layer in the adult mammalian brainProc Natl Acad Sci USA961161911624Google Scholar
  22. Fallon, J, Reid, S, Kinyamu, R, Opole, I, Opole, R, Baratta, J, Korc, M, Endo, TL, Duong, A, Nguyen, G, Karkehabadhi, M, Twardzik, D, Patel, S, Loughlin, S 2000In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brainProc Natl Acad Sci USA971468614691Google Scholar
  23. Frade, JM 2000aNRAGE and the cycling side of the neurotrophin receptor p75Trends Neurosci.23591592Google Scholar
  24. Frade, JM 2000bUnscheduled re-entry into the cell cycle induced by NGF precedes cell death in nascent retinal neuronesJ Cell Sci11311391148Google Scholar
  25. Gage, FH, Ray, J, Fisher, LJ 1995Isolation, characterization, and use of stem cells from the CNSAnnu Rev Neurosci18159192Google Scholar
  26. Giardino, L, Bettelli, C, Calza, L 2000In vivo regulation of precursor cells in the subventricular zone of adult rat brain by thyroid hormone and retinoidsNeurosci Lett2951720Google Scholar
  27. Gould, E, Gross, CG 2002Neurogenesis in adult mammals: some progress and problemsJ Neurosci22619623Google Scholar
  28. Greene, LA, Tischler, AS 1976Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factorProc Natl Acad Sci USA7324242428Google Scholar
  29. Hofstadter, F, Knuchel, R, Ruschoff, J 1995Cell proliferation assessment in oncologyVirchows Arch427323341Google Scholar
  30. Horner, PJ, Power, AE, Kempermann, G, Kuhn, HG, Palmer, TD, Winkler, J, Thal, LJ, Gage, FH 2000Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cordJ Neurosci2022182228Google Scholar
  31. Hosomi, S, Yamashita, T, Aoki, M, Tohyama, M 2003The p75 receptor is required for BDNF-induced differentiation of neural precursor cellsBiochem. Biophys Res Commun30110111015Google Scholar
  32. Jin, K, Zhu, Y, Sun, Y, Mao, XO, Xie, L, Greenberg, DA 2002Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivoProc Natl Acad Sci USA991194611950Google Scholar
  33. Kee, N, Sivalingam, S, Boonstra, R, Wojtowicz, JM 2002The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesisJ Neurosci Methods11597105Google Scholar
  34. Kendall, SE, Goldhawk, DE, Kubu, C, Barker, PA, Verdi, JM 2002Expression analysis of a novel p75(NTR) signaling protein, which regulates cell cycle progression and apoptosisMech. Dev.117187200Google Scholar
  35. Lee, R, Kermani, P, Teng, KK, Hempstead, BL 2001Regulation of cell survival by secreted proneutrophinsScience29419451948Google Scholar
  36. Lendahl, U, Zimmerman, LB, McKay, RD 1990CNS stem cells express a new class of intermediate filament proteinCell60585595Google Scholar
  37. Lie, DC, Dziewczapolski, G, Willhoite, AR, Kaspar, BK, Shults, CW, Gage, FH 2002The adult substantia nigra contains progenitor cells with neurogenic potentialJ Neurosci2266396649Google Scholar
  38. Lois, C, Alvarez-Buylla, A 1994Long-distance neuronal migration in the adult mammalian brainScience26411451148Google Scholar
  39. Lois, C, Garcia-Verdugo, JM, Alvarez-Buylla, A 1996Chain migration of neuronal precursorsScience271978981Google Scholar
  40. Lopez-Sanchez, N, Frade, JM 2002Control of the cell cycle by neurotrophins: lessons from the p75 neurotrophin receptorHistol Histopathol1712271237Google Scholar
  41. Luskin, MB 1993Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zoneNeuron11173189Google Scholar
  42. Markakis, EA, Palmer, TD, Randolph-Moore, L, Rakic, P, Gage, FH 2004Novel neuronal phenotypes from neural progenitor cellsJ Neurosci2428862897Google Scholar
  43. Marshall, CA, Suzuki, SO, Goldman, JE 2003Gliogenic and neurogenic progenitors of the subventricular zone: who are they, where did they come from, and where are they goingGlia435261Google Scholar
  44. Maslov, AY, Barone, TA, Plunkett, RJ, Pruitt, SC 2004Neural stem cell detection, characterization, and age-related changes in the subventricular zone of miceJ Neurosci2417261733Google Scholar
  45. Morshead, CM, Reynolds, BA, Craig, CG, McBurney, MW, Staines, WA, Morassutti, D, Weiss, S, Kooy, D 1994Neural stem cells in the adult mammalian forebrain: a relatively quiescent subpopulation of subependymal cellsNeuron1310711082Google Scholar
  46. Nykjaer, A, Lee, R, Teng, KK, Jansen, P, Madsen, P, Nielsen, MS, Jacobsen, C, Kliemannel, M, Schwarz, E, Willnow, TE, Hempstead, BL, Petersen, CM 2004Sortilin is essential for proNGF-induced neuronal cell deathNature427843848Google Scholar
  47. O’Connor, L, Huang, DC, O’Reilly, LA, Strasser, A 2000Apoptosis and cell divisionCurr Opin Cell Biol12257263Google Scholar
  48. Okano, HJ, Pfaff, DW, Gibbs, RB 1996Expression of EGFR-, p75NGFR-, and PSTAIR (cdc2)-like immunoreactivity by proliferating cells in the adult rat hippocampal formation and forebrainDev Neurosci18199209Google Scholar
  49. Paxinos, G, Watson, C 1986The rat brain in stereotaxic coordinatesAcademic PressSan DiegoGoogle Scholar
  50. Pencea, V, Bingaman, KD, Wiegand, SJ, Luskin, MB 2001Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamusJ Neurosci2167066717Google Scholar
  51. Petreanu, L, Alvarez-Buylla, A 2002Maturation and death of adult-born olfactory bulb granule neurons: role of olfactionJ Neurosci2261066113Google Scholar
  52. Powers, JF, Shahsavari, M, Tsokas, P, Tischler, AS 1999Nerve growth factor receptor signaling in proliferation of normal adult rat chromaffin cellsCell Tissue Res2952132Google Scholar
  53. Rakic, P 2002Adult neurogenesis in mammals: an identity crisisJ Neurosci22614618Google Scholar
  54. Redmond, L, Hockfield, S, Morabito, MA 1996The divergent homeobox gene PBX1 is expressed in the postnatal subventricular zone and interneurons of the olfactory bulbJ Neurosci1629722982Google Scholar
  55. Rifkin, JT, Todd, VJ, Anderson, LW, Lefcort, F 2000Dynamic expression of neurotrophin receptors during sensory neuron genesis and differentiationDev Biol227465480Google Scholar
  56. Salehi, AH, Roux, PP, Kubu, CJ, Zeindler, C, Bhakar, A, Tannis, LL, Verdi, JM, Barker, PA 2000NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosisNeuron27279288Google Scholar
  57. Schliebs, R, Rossne, S, Bigl, V 1996Immunolesion by 192IgG-saporin of rat basal forebrain cholinergic system: a useful tool to produce cortical cholinergic dysfunctionProg Brain Res109253264Google Scholar
  58. Seroogy, KB, Gall, CM, Lee, DC, Kornblum, HI 1995Proliferative zones of postnatal rat brain express epidermal growth factor receptor mRNABrain Res670157164Google Scholar
  59. Song, HJ, Stevens, CF, Gage, FH 2002Neural stem cells from adult hippocampus develop essential properties of functional CNS neuronsNat Neurosci5438445Google Scholar
  60. Stemple, DL, Anderson, DJ 1992Isolation of a stem cell for neurons and glia from the mammalian neural crestCell71973985Google Scholar
  61. Urdiales, JL, Becker, E, Andrieu, M, Thomas, A, Jullien, J, Grunsven, LA, Menut, S, Evan, GI, Martin-Zanca, D, Rudkin, BB 1998Cell cycle phase-specific surface expression of nerve growth factor receptors TrkA and p75(NTR)J Neurosci11867676775Google Scholar
  62. Vaccarino, FM, Schwartz, ML, Raballo, R, Nilsen, J, Rhee, J, Zhou, M, Doetschman, T, Coffin, JD, Wyland, JJ, Hung, YT 1999Changes in cerebral cortex size are governed by fibroblast growth factor during embryogenesisNat Neurosci2246253Google Scholar
  63. Wang, KC, Kim, JA, Sivasankaran, R, Segal, R, He, Z 2002p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OmgpNature4207478Google Scholar
  64. Weiss, S, Dunne, C, Hewson, J, Wohl, C, Wheatley, M, Peterson, AC, Reynolds, BA 1996Multipotent CNS stem cells are present in the adult mammalian spinal cord and ventricular neuroaxisJ Neurosci1675997609Google Scholar
  65. Wu, JP, Kuo, JS, Liu, YL, Tzeng, SF 2000Tumor necrosis factor-alpha modulates the proliferation of neural progenitors in the subventricular/ventricular zone of adult rat brainNeurosci Lett292203206Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • A. Giuliani
    • 1
  • G. D’Intino
    • 1
  • M. Paradisi
    • 1
  • L. Giardino
    • 1
    • 2
  • L. Calzà
    • 1
    • 2
  1. 1.DIMORFIPAUniversity of BolognaOzzano dell’ EmiliaItaly
  2. 2.Pathophysiology Center for the Nervous SystemHesperia HospitalModenaItaly

Personalised recommendations