Aging of Neurons in Culture

  • F. Howard Schneider
  • Suzanne G. Rehnberg
  • Mark P. Bear
Part of the Advances in Behavioral Biology book series (ABBI, volume 23)


Valuable information about cellular and biochemical aspects of aging has been obtained from studies with human and non-human dividing diploid cells in culture (see reviews by Hay, 1970; Hayflick, 1974; Littlefield, 1976 and Orgel, 1973). However, less work has been done using in vitro models to study cellular mechanisms of aging in post-mitotic differentiated cells, such as muscle and nerve. Varon (1975) has recently reviewed the nerve tissue preparations availabe which could possibly be used to study neuronal aging, including organ cultures, nerve tissue explants and reaggregating and dispersed cell cultures. These preparations are especially useful for morphological and electrophysiological studies, but are not as satisfactory for biochemical studies since they consist of a complex mixture of cell types. Furthermore, preparations obtained from mature or very old animals are less likely to yield functionally intact preparations since with age there is an increase in the difficulty of dissociating neuronal tissue into single cells. In view of the difficulties in obtaining preparations of pure nerve cells from animals, we have considered the possibility of using continuous lines of neuroblastoma cells for studies on neuronal aging.


Acid Phosphatase Neuroblastoma Cell Sodium Butyrate Acetylcholinesterase Activity Mouse Neuroblastoma 
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. Amano, T., Richelson, E. and Nirenberg, M. Neurotransmitter synthesis by neuroblastoma clones. Proc. Nat. Acad. Sci. U.S.A. 69:258–263, 1972.CrossRefGoogle Scholar
  2. Anagnoste, B., Freedman, L.S., Goldstein, M., Broome, J. and Fuxe, K. Dopamine-β-hydroxylase activity in mouse neuroblastoma tumors and in cell cultures. Proc. Nat. Acad. Sci. U.S.A. 69:1883–1886, 1972.CrossRefGoogle Scholar
  3. Augusti-Tocco, G. and Sato, G. Establishment of functional clonal lines of neurons from mouse neuroblastoma. Proc. Nat. Acad. Sci. U.S.A. 64:311–315, 1969.CrossRefGoogle Scholar
  4. Baskin, F. and Rosenberg, R.N. Decreased β-mercaptopurine retention by two resistant variants of mouse neuroblastoma with normal hypoxanthine-guanine-phosphoribosyltransferase activities. J. Pharmacol. Exp. Ther. 193:293–300, 1975.PubMedGoogle Scholar
  5. Bear, M.P. and Schneider, F.H. The effect of media pH on the rate of growth, neurite formation and acetylcholinesterase activity in mouse neuroblastoma cells in culture. J. Cellular Physiol., In press, 1976.Google Scholar
  6. Bowman, P.D., Meek, R.L. and Daniel, C.W. Aging of human fibroblasts in vitro. Correlations between DNA synthesis ability and cell size. Exp. Cell Res. 93:184–190, 1975.PubMedCrossRefGoogle Scholar
  7. Breakefield, X.O. Neurotransmitter metabolism in murine neuroblastoma cells. Life Sci. 18:267–278, 1976.PubMedCrossRefGoogle Scholar
  8. Brunk, U., Ericsson, J.L.E., Ponter, J. and Westermark, B. Residual bodies and “aging” in cultured human glial cells. Exp. Cell Res. 79:1–14, 1973.PubMedCrossRefGoogle Scholar
  9. Burstone, M.S. Histochemical demonstration of acid phosphatases with napthol. J. Nat. Cancer Inst. 21:523–539, 1958.PubMedGoogle Scholar
  10. Cristofalo, V.J. Metabolic aspects of aging in diploid human cells. In: Aging in Cell and Tissue, (Eds. E. Holeckova and V.J. Cristofalo), Plenum Press, New York, pp. 83–119, 1970.CrossRefGoogle Scholar
  11. Daems, W.T., Wisse, E. and Brederoo, P. Electron microscopy of the vacuolar apparatus in lysosomes. In: Biology and Pathology, Vol. 1, (Eds. J.T.D. Ingle and H.B. Fell), Am. Elsevier Pub. Co., New York, pp. 97–103, 1969.Google Scholar
  12. Deamer, D.W. and Gonzales, J. Autofluorescent structures in cultured WI-38 cells. Arch. Biochem. Biophys. 165:421–426, 1974.PubMedCrossRefGoogle Scholar
  13. Destrem, H. Essai clinique de la centrophenoxine en geriatrie (52 cas). Presse Med. 69:1999–2001, 1961.PubMedGoogle Scholar
  14. Dunham, L.J. and Stewart, H.L. A survey of transplantable and transmissible tumors. J. of the Nat. Cancer Inst. 13:1299–1377, 1953.Google Scholar
  15. Ellman, G.L., Courtney, K.D., Andres, V. and Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1:88–95, 1961.CrossRefGoogle Scholar
  16. Furmanski, P., Silverman, D.J. and Lubin, M. Expression of differentiated functions in mouse neuroblastoma mediated by dibutyryl-cyclic adenosine monophosphate. Nature 233:413–415, 1971.PubMedCrossRefGoogle Scholar
  17. Gianetto, R. and DeDuve, C. Tissue fractionation studies: comparative study of binding of acid Phosphatase, β-glucuronidase and cathepsin by rat liver particles. Biochemical Journal 59:433–438, 1955.PubMedGoogle Scholar
  18. Glazer, R.I. and Schneider, F.H. Effects of adenosine 3′:5′-Mono-phosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture. J. Biol. Chem. 250:2745–2749, 1975.PubMedGoogle Scholar
  19. Harris, A.J. and Dennis, M.J. Acetylcholine sensitivity and distribution on mouse neuroblastoma cells. Science 167:1253–1255, 1970.PubMedCrossRefGoogle Scholar
  20. Hay, R.J. Cell strain senescence in vitro: Cell culture anomaly or an expression of a fundamental inability of normal cells to survive and proliferate. In: Aging in Cell and Tissue Culture, pp. 7–24, 1970.Google Scholar
  21. Hayflick, L. Cytogerontology. In: Theoretical Aspect of Aging, (Ed. M. Rockstein), Academic Press, New York, pp. 83–103, 1974.Google Scholar
  22. Hinkley, R.E. and Telser, A.G. The effects of halothane on cultured mouse neuroblastoma cells. I. Inhibition of morphological differentiation. J. Cell Biol. 63:531–540, 1974.PubMedCrossRefGoogle Scholar
  23. Kates, J.R., Winterton, R. and Schlessinger, K. Induction of acetylcholinesterase activity in mouse neuroblastoma tissue culture cells. Nature 229:345–347, 1971.PubMedCrossRefGoogle Scholar
  24. Kaukel, E. and Hilz, H. Permeation of dibutyryl-cAMP into HeLa cells and its conversion to monobutyryl cAMP. Biochem. Biophys. Res. Commun. 46:1011–1018, 1972.PubMedCrossRefGoogle Scholar
  25. Lanks, K.W., Dorwin, J.M. and Papirmeister, B. Increased rate of acetylcholinesterase synthesis in differentiating neuroblastoma cells. J. Cell Biol. 63:824–830, 1974.PubMedCrossRefGoogle Scholar
  26. Lipetz, J. and Cristofalo, V.J. Ultrastructural changes accompanying the aging of human diploid cells in culture. J. Ultrastruct. Res. 39:43–56, 1972.PubMedCrossRefGoogle Scholar
  27. Littlefield, J.W. Variation, Senescence and Neoplasia. Harvard University Press, Cambridge, MA., 1976.Google Scholar
  28. Nandy, K. and Bourne, G.H. Effect of centrophenoxine on the lipofuscin pigment in the neurons of senile guinea pigs. Nature (Lond.) 210: 313–314, 1966.CrossRefGoogle Scholar
  29. Nandy, K. and Schneider, F.H. Lipofuscin pigment formation in neuro-blastoma cells in culture. In: Neurobiology of Aging, (Eds. R. D. Terry and S. Gershon), Raven Press, New York, pp. 245–264, 1976.Google Scholar
  30. Nelson, P.G., Peacock, J.H. and Amano, T. Responses of neuroblastoma cells to iontophoretically applied acetylcholine. J. Cell Physiol. 77:353–362, 1971.PubMedCrossRefGoogle Scholar
  31. Orgel, L.E. Ageing of clones of mammalian cells. Nature 243:441–445, 1973.PubMedCrossRefGoogle Scholar
  32. Peacock, J.H., McMorris, F.A. and Nelson, P.G. Electrical excitability and chemosensitivity of mouse neuroblastoma X mouse on human fibroblast hybrids. Expl. Cell Res. 79:199–212, 1973.CrossRefGoogle Scholar
  33. Prasad, K.N. Differentiation of neuroblastoma cells in culture. Biol. Rev. 50:129–165, 1975.PubMedCrossRefGoogle Scholar
  34. Prasad, K.N. and Hsie, A.W. Morphological differentiation of mouse neuroblastoma cells induced in vitro by dibutyryl adenosine 3′:5′-cyclic monophosphate. Nature New Biology 233:141–142, 1971.PubMedGoogle Scholar
  35. Prasad, K.N. and Vernadakis, A. Morphological and biochemical study in x-ray and dibutyryl cyclic AMP-induced differentiated neuroblastoma cells. Exp. Cell Res. 70:27–32, 1972.PubMedCrossRefGoogle Scholar
  36. Robbins, E., Levine, E.M. and Eagle, H. Morphologic changes accompanying senescence of cultured human diploid cells. J. Expl. Med. 131:1211–1222, 1970.CrossRefGoogle Scholar
  37. Schneider, F.H. Effects of sodium butyrate on mouse neuroblastoma cells in culture. Biochem. Pharmacol. 25:2309–2317, 1976.PubMedCrossRefGoogle Scholar
  38. Schubert, D., Humphreys, S., Baroni, C. and Cohn, M. In vitro differentiation of a mouse neuroblastoma. Proc. Natl. Acad. Sci. U.S.A. 64:316–323, 1969.PubMedCrossRefGoogle Scholar
  39. Siakotos, A.N. and Armstrong, D. Age pigment, a biochemical indicator of intracellular aging. In: Neurobiology of Aging, (Eds. J. M. Ordy and K.R. Brizzee), Plenum Press, New York, pp. 369–399, 1975.Google Scholar
  40. Simantov, R. and Sachs, L. Regulation of acetylcholine receptors in relation to acetylcholinesterase in neuroblastoma cells. Proc. Natl. Acad. Sci. U.S.A. 70:2902–2905, 1973.PubMedCrossRefGoogle Scholar
  41. Simons, J.W.I.M. The use of frequency distribution of cell diameters to characterize cell populations in tissue cultures. Exp. Cell Res. 45:336–350, 1967.PubMedCrossRefGoogle Scholar
  42. Soukapova, M., Holeckova, E. and Hnevkovsky, P. Changes of the latent period of explanted tissues during ontogenesis of aging. In: Cell and Tissue Culture, (Eds. E. Holeckova and V. J. Cristofalo), Plenum Press, New York, pp. 41–56, 1970.Google Scholar
  43. Thuillier, G., Rumpf, P. and Thuillier, J. Preparation et. etude pharmacologique preliminaire des esters dimethylaminoethyliques de divers acides agissant comme regulateurs de croissance des vegetaux. Compt. Rend. Heb. Sean. L’Acad. Sci. Paris 249:2081–2083, 1959.Google Scholar
  44. Toth, S.E. The origin of lipofuscin age pigments. Exp. Gerontol. 3:19–30, 1968.PubMedCrossRefGoogle Scholar
  45. Varon, S. In vitro approaches to the study of neural tissue agingo In: Survey Report on the Aging Nervous System, (Ed. G.J. Maletta), U.S. Government Printing Office, Washington, D.C., pp. 59–76, 1975.Google Scholar
  46. Waymire, J.C., Weiner, N. and Prasad, K.N. Regulation of tyrosine hydroxylase activity in cultured mouse neuroblastoma cells: Elevation induced by analogs of adenosine 3′:5′-cyclic mono-phosphate. Proc. Nat. Acad. Sci. U.S.A. 69:2241–2245, 1972.CrossRefGoogle Scholar
  47. Wood, A.W., Becker, M.A., Minna, J.D. and Seegmiller, J.E. Purine metabolism in normal and thioguanine resistant neuroblastoma. Proc. Nat. Acad. Sci. U.S.A. 70:3880–3883, 1973.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • F. Howard Schneider
    • 1
  • Suzanne G. Rehnberg
    • 1
  • Mark P. Bear
    • 1
  1. 1.Geriatric Research, Educational and Clinical CenterVeterans Administration HospitalBedfordUSA

Personalised recommendations