Primary Cultures of Adult Mammalian Sensory Neurons and Other in Vitro Systems of Use in Neurotoxicological Studies

  • R. A. Smith
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 14)


There has been a significant trend in recent years, from not only within scientific and medical communities but also from a wide spectrum of social, ethical, political and commercial concerns, to seek reliable alternatives to whole animal experimentation in toxicological research. The impetus for adapting and developing methodologies to reduce, if not replace, the numbers of animals used is as great in studying substances potentially toxic to the complex nervous system as for agents to other target organs. Stringent validation is required before acceptance of in vitro methods in the predictive screening of new compounds, and this is well recognised by workers in the field (e.g. Atterwill & Steele 1987; Shahar & Goldberg 1987; Mehlman et al 1989). In vitro approaches do exist, which are capable of generating data on the mechanisms underlying acute toxicity. These permit precisely defined dosing in controlled environments, which is not possible in most in vivo studies, and are relatively quick and inexpensive to carry out. It is in mechanistic studies that cell and tissue culture can be of most value.


Dorsal Root Ganglion Dorsal Root Ganglion Neuron Cytosine Arabinoside Neural Cell Line Cytosine Arabinoside 
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  1. Atterwill CK, Steele CE (1987) In vitro methods in toxicology. C.U.P., CambridgeCrossRefGoogle Scholar
  2. Ericsson A-Ch, Walum E (1984) Cytotoxicity of cyclophosphamide and acrylamide in glioma and neuroblastoma cell lines cocultured with liver cells. Toxicol Letters 20:251–256CrossRefGoogle Scholar
  3. Greenberg DA, Carpenter CL, Messing RO (1987) Ethanol-induced component of Ca uptake in PC12 cells is sensitive to Ca channel modulating drugs. Brain Res 410:143–146PubMedCrossRefGoogle Scholar
  4. Greene RW, Haas HL, Hermann A (1985) Effects of caffeine on hippocampal pyramidal cells in vitro. Br J Pharmac 85: 163–169Google Scholar
  5. Honeggar P, Richelson E (1977) Kainic acid alters neurochemical development in fetal rat brain aggregating cell cultures. Brain Res 138:580–584CrossRefGoogle Scholar
  6. Khera KS, Whalen C (1988) Detection of neuroteratogens with an in vitro cytotoxicity assay using primary monolayers cultured from dissociated fetal rat brains. Toxic in Vitro 2:257–273CrossRefGoogle Scholar
  7. Koh JY, Goldberg MP, Hartley DM, Choi DW (1990) Non-NMDA receptor-mediated neurotoxicity in cortical culture. J Neurosci 10:693–705PubMedGoogle Scholar
  8. Kontur PJ, Hoffmann PC, Heller A (1987) Neurotoxic effects of methamphetamine assessed in three-dimensional reaggregate tissue cultures. Dev Brain Res 31:7–14CrossRefGoogle Scholar
  9. Martin DP, Wallace TL, Johnson EM (1990) Ara-C kills postmitotic neurons in a fashion resembling trophic factor deprivation: Evidence that a deoxycytidine-dependent process is required for NGF signal transduction. J Neurosci 10:184–193PubMedGoogle Scholar
  10. Mehlman MA, Pfitzer EA, Scala RA (1989) A report on methods to reduce, refine and replace animal testing in industrial toxicology laboratories. Cell Biol Toxicol 5:349–358PubMedCrossRefGoogle Scholar
  11. Mithen FA, Reiker MM, Birchem R (1990) Effects of ethanol on rat Schwann cell proliferation and myelination in culture. In Vitro Cell Dev Biol 26:129–139PubMedCrossRefGoogle Scholar
  12. Oakes SG, Pozos, RS (1982) Electrophysiologic effects of acute ethanol exposure. I. Alterations in the action potentials of DRG neurons in dissociated culture. Dev Brain Res 5:243–249CrossRefGoogle Scholar
  13. Orr DJ, Smith RA (1988) Neuronal maintenance and neurite extension in non-neuronal cellreduced culture is dependent on substratum coating. J Cell Sci 91:555–561PubMedGoogle Scholar
  14. Pannese E, Ledda M, Conte V, Procacci P, Matsuda S (1990) SEM observations of the perikaryal projections of rabbit spinal ganglion neurons after enzymatic removal of connective tissue and satellite cells. Cell Tiss Res 260: 167–173CrossRefGoogle Scholar
  15. Schoenen J, Delree P, Leprince P, Moonen G (1989) Neurotransmitter phenotype plasticity in cultured dissociated adult rat DRG: An immunocytochemical study. J Neurosci Res 22:473–487PubMedCrossRefGoogle Scholar
  16. Scott BS, Edwards BAV (1981) The effect of chronic ethanol exposure on the electric membrane properties of DRG neurons in cell culture. J Neurobiol 12:379–390PubMedCrossRefGoogle Scholar
  17. Scott BS, Petit TL, Lew J (1986) Differential survival of fetal and adult neurons and nonneuronal cells exposed chronically to ethanol in cell culture. Neurotoxicol 7:81–90Google Scholar
  18. Shahar A, Goldberg A (1987) Model systems in neurotoxicolog-Alternative approaches to animal testing. AR Liss, New YorkGoogle Scholar
  19. Skerritt JH, Werz MA, McLean MJ, Macdonald RL (1984) Diazepam and its anomalous p-chloro-derivative Ro 5–4864: Comparative effects on mouse neurons in culture. Brain Res 310: 99–105PubMedCrossRefGoogle Scholar
  20. Smith RA, McInnes IE (1986) Phase contrast and electron microscopical observations of adult mouse DRG cells maintained in primary culture. J Anat 145:1–12PubMedGoogle Scholar
  21. Smith RA, Orr DJ (1987) The survival of adult mouse sensory neurons in vitro is enhanced by natural and synthetic substrata, particularly fibronectin. J Neurosci Res 17:265–270PubMedCrossRefGoogle Scholar
  22. Smith RA, Orr DJ, McInnes IE (1987) A refined primary culture system of adult mouse sensory neurons for neurotoxicity testing. In Shahar A, Goldberg A (eds) Model systems in neurotoxicology-Alternative approaches to animal testing. Alan R Liss Inc, New York, pp 69–75Google Scholar
  23. Smith RA, Orr DJ, Haetzman ML, MacPherson N, Storey ND (1990) The response of primary cultured adult mouse sensory neurons to ethanol, propanol, acetaldehyde and acrolein treatments. Virchows Arch (B) 58: 323–330CrossRefGoogle Scholar
  24. Spencer PS, Peterson ER, Madrid R, Raine CS (1978) Effects of thallium salts on neuronal mitochondria in organotypic cord-ganglia-muscle combination cultures. J Cell Biol 58:79–95CrossRefGoogle Scholar
  25. White G, Lovinger DM, Weight FF (1990) Ethanol inhibits NMDA-activated current but does not alter GABA-activated current in an isolated adult mammalian neuron. Brain Res 507: 332–336PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • R. A. Smith
    • 1
  1. 1.Department of AnatomyUniversity of GlasgowGlasgowScotland

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