Skip to main content

Advertisement

Log in

Age-Related Changes of NADPH-Diaphorase Positivity in the Rat Rostral Migratory Stream

  • Original Research
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

Accumulating evidence confirms that nitric oxide (NO), a versatile diffusible signaling molecule, contributes to controling of adult neurogenesis. We have previously shown the timing of NADPH-diaphorase (NADPH-d) positivity within the rat rostral migratory stream (RMS) during the first postnatal month. The present study was designed to describe further age-related changes of NO presence in this neurogenic region. The presence of NO synthesizing cells in the RMS was shown by NADPH-d histochemistry and neuronal nitric oxide synthase (nNOS) immunohistochemistry. The phenotypic identity of nitrergic cells was examined by double labeling with GFAP and NeuN. Systematic qualitative and quantitative analysis of NADPH-d-positive cells was performed in the neonatal (P14), adult(5 months) and aging (20 months) rat RMS.

1. Nitrergic cells with different distribution pattern and morphological characteristics were present in the RMS at all ages examined. In neonatal animals, small, moderately stained NADPH-d-positive cells were identified in the RMS vertical arm and in the RMS elbow. In adult and aging rats a few labeled cells could be also detected in the RMS horizontal arm. NADPH-d-positive cells in adult and aging rats were characterized by long varicose processes and displayed dark labeling in comparison to the neonatal group.

2. Double immunolabeling has revealed that nNOS-immunoreactivity co-localized with that of NeuN. This indicates that nitrergic cells within the RMS are neurons.

3. Quantitative analysis showed that the number of NADPH-d-positive cells increases with advancing age.

The presence of NO producing cells in the RMS of neonatal adult and aging rats indicates, that this proliferating and migratory area is under the influence of NO throughout the entire life of the animals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Altman, J. (1969). Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. J. Comp. Neurol. 137:433–458.

    Article  CAS  PubMed  Google Scholar 

  • Blottner, D., Grozdanovic, Z., and Gossrau, R. (1995). Histochemistry of nitric oxide synthase in the nervous system. Histochem. J. 27:785–811.

    Article  CAS  PubMed  Google Scholar 

  • Bredt, D. S., and Snyder, S. H. (1994). Transient nitric oxide synthase neurons in embryonic cerebral cortical plate, sensory ganglia, and olfactory epithelium. Neuron 13:301–313.

    Article  CAS  PubMed  Google Scholar 

  • Cornwell, T. L., Arnold, E., Boerth, N. J., and Lincoln, T. M. (1994). Inhibition of smooth muscle cell growth by nitric oxide and activation of camp-dependent protein kinase by cGMP. Am. J. Physiol. 267:C1405–C1413.

    CAS  PubMed  Google Scholar 

  • Dawson, T. M., Bredt, D. S., Fotuhi, M., Hwang, P. M., and Snyder, S. H. (1991). Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc. Natl. Acad. Sci. USA 88:7797–7801.

    CAS  PubMed  Google Scholar 

  • Fujiyama, F., and Masuko, S. (1996). Association of dopaminergic terminals and neurons releasing nitric oxide in the rat striatum: An electron microscopic study using NADPH-diaphorase histochemistry and tyrosine hydroxylase immunohistochemistry. Brain Res. Bull. 40:121–127.

    Article  CAS  PubMed  Google Scholar 

  • Gally, J. A., Montague, P. R., Reeke, G. N., and Edelman, G. M., Jr. (1990). The NO hypothesis: Possible effects of a short-lived, rapidly diffusible signal in the development and function of the nervous system. Proc. Natl. Acad. Sci. USA 87:3547–3551.

    CAS  PubMed  Google Scholar 

  • Giuili, G., Luzi, A., Poyard, M., and Guellaën, G. (1994). Expression of mouse brain soluble guanylyl cyclase and NO synthase during ontogeny. Dev. Brain Res. 81:269–283.

    Article  CAS  Google Scholar 

  • Hope, B. T., Michael, G. J., Knigge, K. M., and Vincent, S. R. (1991). Neuronal NADPH-diaphorase is a nitric oxide synthase. Proc. Natl. Acad. Sci. USA 88:2811–2814.

    CAS  PubMed  Google Scholar 

  • Hopewell, J. W. (1971). A quantitative study of the mitotic activity in the subependymal plate of adult rats. Cell Tissue Kinet. 4:233–238.

    CAS  PubMed  Google Scholar 

  • Jankovski, A., and Sotelo, C. (1996). Subventricular zone-olfactory bulb migratory pathway in the adult mouse: Cellular composition and specificity as determined by heterochronic and heterotopic transplantation. J. Comp. Neurol. 371:376–396.

    Article  CAS  PubMed  Google Scholar 

  • Kuzin, B., Roberts, I., Peunova, N., and Enikolopov, G. (1996). Nitric oxide regulates cell proliferation during drosophila development. Cell 87:639–649.

    Article  CAS  PubMed  Google Scholar 

  • Lois, C., and Alvarez-Buylla, A. (1993). Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia. Proc. Natl. Acad. Sci. USA 90:2074–2077.

    CAS  PubMed  Google Scholar 

  • Lois, C., and Alvarez-Buylla, A. (1994). Long-distance neuronal migration in the adult mammalian brain. Science 264:1145–1148.

    CAS  PubMed  Google Scholar 

  • Lois, C., Garcia-Verdugo, J., and Alvarez-Buylla, A. (1996). Chain migration of neuronal precursors. Science 271:978–981.

    CAS  PubMed  Google Scholar 

  • Luskin, M. B. (1993). Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone. Neuron 11:173–189.

    Article  CAS  PubMed  Google Scholar 

  • Martoncikova, M., Orendacova, J., Racekova, E., and Pousova, B. (2004). FENS Abstr. 2:A145.15.

    Google Scholar 

  • Matarredona, E. R., Murillo-Carretero, M., Moreno-López, B., and Estrada, C. (2004). Nitric oxide synthesis inhibition increases proliferation of neural precursors isolated from the postnatal mouse subventricular zone. Brain Res. 995:274–284.

    Article  CAS  PubMed  Google Scholar 

  • Matsui, T., Nagafuji, T., Kumanishi, T., and Asano, T. (1999). Role of nitric oxide in pathogenesis underlying ischemic cerebral damage. Cell. Mol. Neurobiol. 19:177–189.

    Article  CAS  PubMed  Google Scholar 

  • Menezes, J. R. L., Smith, C. M., Nelson, K. C., and Luskin, M. B. (1995). The division of neuronal progenitor cells during migration in the neonatal mammalian forebrain. Mol. Cell Neurosci. 6:496–508.

    Article  CAS  PubMed  Google Scholar 

  • Moreno-López, B., Noval, J. A., González-Bonet, L. G., and Estrada, N. C. (2000). Morphological bases for a role of nitric oxide in adult neurogenesis. Brain Res. 869:244–250.

    PubMed  Google Scholar 

  • Moreno-López, B., Romero-Grimaldi, C., Noval, J. A., Murillo-Carretero, M., Matarredona, E. R., and Estrada, C. (2004). Nitric oxide is a physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb. J. Neurosci. 24:85–95.

    PubMed  Google Scholar 

  • Murillo-Carretero, M., Ruano, M. J., Matarredona, E. R., Villalobo, A., and Estrada, C. (2002). anti-proliferative effect of nitric oxide on epidermal growth factor-responsive human neuroblastome cells. J. Neurochem. 83:119–131.

    Article  CAS  PubMed  Google Scholar 

  • Nakashima, M. N., Yamashita, K., Kataoka, Y., Yamashita, Y. S., and Niwa, M. (1995). Time course of nitric oxide synthase activity in neuronal, glial and endothelial cells of rat striatum following focal cerebral ischemia. Cell. Mol. Neurobiol. 15:341–349.

    Article  CAS  PubMed  Google Scholar 

  • Packer, M. A., Stasiv, Y., Benraiss, A., Chmielnicki, E., Grinberg, A., Westphal, H., Goldman, S. A., and Enikolopov, G. (2003). Nitric oxide negatively regulates mammalian adult neurogenesis. Proc. Natl. Acad. Sci. USA 100:9566–9571.

    Article  CAS  PubMed  Google Scholar 

  • Patterson, J. A., Privat, A., Ling, E. A., and Leblond, C. P. (1973). Transformation of subependymal cells into glial cells as shown by radioautography after 3H-thymidine injection into the lateral ventricle of the brain of young rats. J. Comp. Neurol. 149:183–205.

    Google Scholar 

  • Peunova, N., Scheinker, V., Cline, H., and Enikolopov, G. (2001). Nitric oxide is an essential regulator of cell proliferation in Xenopus brain. J. Neurosci. 21:8809–8818.

    CAS  PubMed  Google Scholar 

  • Racekova, E., Orendacova, J., Martoncikova, M., and Vanicky, I. (2003). NADPH-diaphorase positivity in the rostral migratory stream of the developing rat. Dev. Brain Res. 146:131–134.

    CAS  Google Scholar 

  • Santacana, M., Uttenthal, L. O., Bentura, M. L., Fernández, A. P., Serrano, J., Martinez de Velasco, J., Alonso, D., Martinez-Murillo, R., and Rodrigo, J. (1998). Expression of neuronal nitric oxide synthase during embryonic development of the rat cerebral cortex. Dev. Brain Res. 111:105–222.

    Article  Google Scholar 

  • Scherer-Singler, U., Vincent, S. R., Kimura, H., and McGeer, E. G. (1983). Demonstration of a unique population of neurons with NADPH diaphorase histochemistry. J. Neurosci. Methods 8:229–234.

    Google Scholar 

  • Smart, I. (1961). The subependymal layer of the mouse brain and its cell production as shown by radioautography after thymidine-H3 injection. J. Comp. Neurol. 116:325–338.

    Google Scholar 

  • Tropepe, V., Craig, C. G., Moreshead, C. M., and van der Kooy, D. (1997). Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma. J. Neurosci. 17:7850–7859.

    CAS  PubMed  Google Scholar 

  • Vincent, S. R. (1994). Nitric oxide: A radical neurotransmitter in the central nervous system. Prog. Neurobiol. 42:129–160.

    Article  CAS  PubMed  Google Scholar 

  • Vincent, A. M., and Maise, K. (1999). Nitric oxide induction of neuronal endonuclease activity in programmed cell death. Exp. Cell Res. 246:290–300.

    Article  CAS  PubMed  Google Scholar 

  • Wu, H. H., William, C. V., and McLoon, S. C. (1994). Involvement of nitric oxide in the elimination of a transient retinotectal projection in development. Science 265:1593–1596.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Enikö Račeková.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Račeková, E., Martončíková, M., Mitrušková, B. et al. Age-Related Changes of NADPH-Diaphorase Positivity in the Rat Rostral Migratory Stream. Cell Mol Neurobiol 25, 1093–1105 (2005). https://doi.org/10.1007/s10571-005-8191-9

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-005-8191-9

Key Words

Navigation