Estamos trabajando para incorporar este artículo al repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor


Neural stem cells (NSCs) of the olfactory epithelium (OE) are responsible for tissue maintenance and the neural regeneration after severe damage of the tissue. In the normal OE, NSCs are located in the basal layer, olfactory receptor neurons (ORNs) mainly in the middle layer, and sustentacular (SUS) cells in the most apical olfactory layer. In this work, we induced severe damage of the OE through treatment with a zinc sulfate (ZnSO4) solution directly in the medium, which resulted in the loss of ORNs and SUS cells, but retention of the basal layer. During recovery following injury, the OE exhibited increased proliferation of NSCs and rapid neural regeneration. After 24 h of recovery, new ORNs and SUS cells were observed. Normal morphology and olfactory function were reached after 168 h (7 days) of recovery after ZnSO4 treatment. Taken together, these data support the hypothesis that NSCs in the basal layer activate after OE injury and that these are sufficient for complete neural regeneration and olfactory function restoration. Our analysis provides histological and functional insights into the dynamics between olfactory neurogenesis and the neuronal integration into the neuronal circuitry of the olfactory bulb that restores the function of the olfactory system. © 2016.


Documento: Artículo
Título:Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage
Autor:Frontera, J.L.; Raices, M.; Cervino, A.S.; Pozzi, A.G.; Paz, D.A.
Filiación:Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Neural stem cells; Neurogenesis; Olfaction; Olfactory injury; Olfactory receptor neurons; zinc sulfate; zinc sulfate; animal cell; animal experiment; animal model; animal tissue; Article; basal cell; basement membrane; cell activation; cell loss; cell maturation; cell proliferation; cell regeneration; cell structure; cells; cellular distribution; concentration (parameters); controlled study; convalescence; embryo; epithelium cell; nerve cell differentiation; nerve regeneration; neural stem cell; neuroepithelium; nonhuman; olfactory bulb; olfactory epithelium; olfactory nerve injury; olfactory receptor; priority journal; sensory stimulation; smelling; sustentacular cell; tadpole; thickness; tissue regeneration; tissue structure; Xenopus laevis; animal; cheek; drug effects; growth, development and aging; nervous system development; olfactory mucosa; olfactory receptor neuron; physiology; Animals; Cell Proliferation; Cheek; Nerve Regeneration; Neural Stem Cells; Neurogenesis; Olfactory Bulb; Olfactory Mucosa; Olfactory Receptor Neurons; Xenopus laevis; Zinc Sulfate
Página de inicio:1
Página de fin:9
Título revista:Journal of Chemical Neuroanatomy
Título revista abreviado:J. Chem. Neuroanat.
CAS:zinc sulfate, 7733-02-0; Zinc Sulfate


  • Beites, C.L., Kawauchi, S., Crocker, C.E., Calof, A.L., Identification and molecular regulation of neural stem cells in the olfactory epithelium (2005) Exp. Cell Res., 306, pp. 309-316
  • Brann, J.H., Firestein, S.J., A lifetime of neurogenesis in the olfactory system (2014) Front. Neurosci., 8, p. 182
  • Burd, G.D., Morphological study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb (1993) Microsc. Res. Tech., 24, pp. 195-213
  • Calof, A.L., Chikaraishi, D.M., Analysis of neurogenesis in a mammalian neuroepithelium: proliferation and differentiation of an olfactory neuron precursor in vitro (1989) Neuron, 3, pp. 115-127
  • Calof, A.L., Bonnin, A., Crocker, C., Kawauchi, S., Murray, R.C., Shou, J., Wu, H.H., Progenitor cells of the olfactory receptor neuron lineage (2002) Microsc. Res. Tech., 58, pp. 176-188
  • Cancalon, P., Degeneration and regeneration of olfactory cells induced by ZnSO4 and other chemicals (1982) Tissue Cell, 14, pp. 717-733
  • Cancalon, P., Influence of a detergent on the catfish olfactory mucosa (1983) Tissue Cell, 15, pp. 245-258
  • Cancalon, P.F., Survival and subsequent regeneration of olfactory neurons after a distal axonal lesion (1987) J. Neurocytol., 16, pp. 829-841
  • Deban, S.M., Olson, W.M., Suction feeding by a tiny predatory tadpole (2002) Nature, 420, pp. 41-42
  • Dittrich, K., Kuttler, J., Hassenklover, T., Manzini, I., Metamorphic remodeling of the olfactory organ of the African clawed frog, Xenopus laevis (2015) J. Comp. Neurol.
  • Duggan, C.D., Ngai, J., Scent of a stem cell (2007) Nat. Neurosci., 10, pp. 673-674
  • Farbman, A.I., Developmental biology of olfactory sensory neurons (1994) Semin. Cell Biol., 5, pp. 3-10
  • Frontera, J.L., Cervino, A.S., Jungblut, L.D., Paz, D.A., Brain-derived neurotrophic factor (BDNF) expression in normal and regenerating olfactory epithelium of Xenopus laevis (2014) Ann. Anat., 198, pp. 41-48
  • Graziadei, G.A., Graziadei, P.P., Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy (1979) J. Neurocytol., 8, pp. 197-213
  • Graziadei, P.P., DeHan, R.S., Neuronal regeneration in frog olfactory system (1973) J. Cell Biol., 59, pp. 525-530
  • Gurdon, J.B., Normal table of Xenopus laevis (Daudin) (1994) Trends Genet., 11, p. 418
  • Harding, J., Graziadei, P.P., Monti Graziadei, G.A., Margolis, F.L., Denervation in the primary olfactory pathway of mice. IV. Biochemical and morphological evidence for neuronal replacement following nerve section (1977) Brain Res., 132, pp. 11-28
  • Hassenklover, T., Schwartz, P., Schild, D., Manzini, I., Purinergic signaling regulates cell proliferation of olfactory epithelium progenitors (2009) Stem Cells, 27, pp. 2022-2031
  • Heer, T., Yovanovich, C.A., Pozzi, A.G., Paz, D.A., Galanin: presence and distribution in the brain and pituitary of Rhinella arenarum (Amphibia: Anura) during development (2008) Tissue Cell, 40, pp. 333-342
  • Herzog, C., Otto, T., Regeneration of olfactory receptor neurons following chemical lesion: time course and enhancement with growth factor administration (1999) Brain Res., 849, pp. 155-161
  • Holbrook, E.H., Iwema, C.L., Peluso, C.E., Schwob, J.E., The regeneration of P2 olfactory sensory neurons is selectively impaired following methyl bromide lesion (2014) Chem. Senses, 39, pp. 601-616
  • Holcomb, J.D., Mumm, J.S., Calof, A.L., Apoptosis in the neuronal lineage of the mouse olfactory epithelium: regulation in vivo and in vitro (1995) Dev. Biol., 172, pp. 307-323
  • Huard, J.M., Schwob, J.E., Cell cycle of globose basal cells in rat olfactory epithelium (1995) Dev. Dyn., 203, pp. 17-26
  • Iqbal, T., Byrd-Jacobs, C., Rapid degeneration and regeneration of the zebrafish olfactory epithelium after Triton X-100 application (2010) Chem. Senses, 35, pp. 351-361
  • Iwai, N., Zhou, Z., Roop, D.R., Behringer, R.R., Horizontal basal cells are multipotent progenitors in normal and injured adult olfactory epithelium (2008) Stem Cells, 26, pp. 1298-1306
  • Jang, W., Youngentob, S.L., Schwob, J.E., Globose basal cells are required for reconstitution of olfactory epithelium after methyl bromide lesion (2003) J. Comp. Neurol., 460, pp. 123-140
  • Joiner, A.M., Green, W.W., McIntyre, J.C., Allen, B.L., Schwob, J.E., Martens, J.R., Primary cilia on horizontal basal cells regulate regeneration of the olfactory epithelium (2015) J. Neurosci., 35, pp. 13761-13772
  • Jungblut, L.D., Pozzi, A.G., Paz, D.A., A putative functional vomeronasal system in anuran tadpoles (2012) J. Anat., 221, pp. 364-372
  • Leung, C.T., Coulombe, P.A., Reed, R.R., Contribution of olfactory neural stem cells to tissue maintenance and regeneration (2007) Nat. Neurosci., 10, pp. 720-726
  • Mombaerts, P., Odorant receptor gene choice in olfactory sensory neurons: the one receptor-one neuron hypothesis revisited (2004) Curr. Opin. Neurobiol., 14, pp. 31-36
  • Pozzi, A.G., Yovanovich, C.A., Jungblut, L., Heer, T., Paz, D.A., Immunohistochemical localization of vascular endothelial growth factor and its receptor Flk-1 in the amphibian developing principal and accessory olfactory system (2006) Anat. Embryol. (Berl.), 211, pp. 549-557
  • Quick, Q.A., Serrano, E.E., Cell proliferation during the early compartmentalization of the Xenopus laevis inner ear (2007) Int. J. Dev. Biol., 51, pp. 201-209
  • Ryerson, W.G., Deban, S.M., Buccal pumping mechanics of Xenopus laevis tadpoles: effects of biotic and abiotic factors (2010) J. Exp. Biol., 213, pp. 2444-2452
  • Schnittke, N., Herrick, D.B., Lin, B., Peterson, J., Coleman, J.H., Packard, A.I., Jang, W., Schwob, J.E., Transcription factor p63 controls the reserve status but not the stemness of horizontal basal cells in the olfactory epithelium (2015) Proc. Natl. Acad. Sci. U. S. A., 112, pp. E5068-5077
  • Schwob, J.E., Neural regeneration and the peripheral olfactory system (2002) Anat. Rec., 269, pp. 33-49
  • Wang, Y.Z., Plane, J.M., Jiang, P., Zhou, C.J., Deng, W., Concise review: quiescent and active states of endogenous adult neural stem cells: identification and characterization (2011) Stem Cells, 29, pp. 907-912
  • White, E.J., Kounelis, S.K., Byrd-Jacobs, C.A., Plasticity of glomeruli and olfactory-mediated behavior in zebrafish following detergent lesioning of the olfactory epithelium (2015) Neuroscience, 284, pp. 622-631
  • Williams, S.K., Franklin, R.J.M., Barnett, S.C., Response of olfactory ensheathing cells to the degeneration and regeneration of the peripheral olfactory system and the involvement of the neuregulins (2004) J. Comp. Neurol., 470, pp. 50-62
  • Wu, M., Gerhart, J., Raising Xenopus in the laboratory (1991) Methods Cell Biol., 36, pp. 3-18
  • Yovanovich, C.A., Jungblut, L.D., Heer, T., Pozzi, A.G., Paz, D.A., Amphibian larvae and zinc sulphate: a suitable model to study the role of brain-derived neurotrophic factor (BDNF) in the neuronal turnover of the olfactory epithelium (2009) Cell Tissue Res., 336, pp. 1-9


---------- APA ----------
Frontera, J.L., Raices, M., Cervino, A.S., Pozzi, A.G. & Paz, D.A. (2016) . Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage. Journal of Chemical Neuroanatomy, 77, 1-9.
---------- CHICAGO ----------
Frontera, J.L., Raices, M., Cervino, A.S., Pozzi, A.G., Paz, D.A. "Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage" . Journal of Chemical Neuroanatomy 77 (2016) : 1-9.
---------- MLA ----------
Frontera, J.L., Raices, M., Cervino, A.S., Pozzi, A.G., Paz, D.A. "Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage" . Journal of Chemical Neuroanatomy, vol. 77, 2016, pp. 1-9.
---------- VANCOUVER ----------
Frontera, J.L., Raices, M., Cervino, A.S., Pozzi, A.G., Paz, D.A. Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage. J. Chem. Neuroanat. 2016;77:1-9.