Abstract
Selective destruction of neurons based on the use of targeted toxins has proven successful for several types of neurons (1). This chapter will describe the use of an immunotoxin to selectively destroy rat neurons that express the low-affinity neurotrophin receptor (p75NTR) (2). This immunotoxin consists of a monoclonal antibody disulfide coupled to a ribosome inactivating protein. The most extensively used and studied version uses the antibody 192 IgG originally developed as an antibody to a rat NGF-binding protein (3). 192 IgG has been extensively used to study rat p75NTR. Results of these studies have demonstrated p75NTR expression on a variety of neurotrophin-responsive cells, including sympathetic ganglion neurons, some primary sensory neurons, and cholinergic neurons of the basal forebrain. p75NTR also is expressed on cells not known to be responsive to neurotrophins, such as cerebellar Purkinje neurons and numerous other tissues during development (4). Thus, producing selective lesions using 192 IgG also requires restricting application of the immunotoxin to the region of the target cells.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Wiley, R. G. and Lappi, D. A. (1994) Suicide transport and immunolesioning. R.G. Landes Co., Austin, TX.
Wiley, R. G., Oeltmann, T. N., and Lappi, D. A. (1991) Immunolesioning: selective destruction of neurons using immunotoxin to rat NGF receptor. Brain Res. 562, 149–153.
Chandler, C. E., Parsons, L. M., Hosang, M., and Shooter, E. M. (1984) A monoclonal antibody modulates the interaction of nerve growth factor with PC 12 cells. J. Biol. Chem. 259, 6882–6889.
Cuello, A. C., Pioro, E. P., and Ribeiro-da-Silva, A. (1990) Cellular and subcellular localization of nerve growth factor receptor-like immunoreactivity in the rat CNS. Neurochem. Int. 17, 205–213.
Endo, Y., Mitsui, K., Motizuki, M., and Tsurugi, K. (1987) The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. J. Biol. Chem. 262, 5908–5912.
Eiklid, K., Olsnes, S., and Pihl, A. (1980) Entry of lethal doses of abrin, ricin and modeccin into the cytosol of HeLa cells. Exp. Cell Res. 126, 321–326.
Wiley, R. G. (1992) Neural lesioning with ribosome-inactivating proteins: suicide transport and immunolesioning. Trends Neurosci. 15, 285–290.
Siegall, C. B., Wolff, E. A., Gawlak, S. L., Paul, L., Chace, D., and Mixan, B. (1995) Immunotoxins as cancer chemotherapeutic agents. Drug Dev. Res. 34, 210–219.
Lappi, D. A., Esch, F. S., Barbieri, L., Stirpe, F., and Soria, M. (1985) Characterization of a Saponaria officinalis seed ribosome-inactivating protein: immunoreactivity and sequence homologies. Biochem. Biophys. Res. Commun. 129, 934–942.
Wiley, R. G. (1997) Findings about the cholinergic basal forebrain using immunotoxin to the nerve growth factor receptor. Ann. NY Ac ad. Sci. 835, 20–29.
Wiley, R. G. and Lappi, D. A. (1997) Destruction of neurokinin-1 receptor expressing cells in vitro and in vivo using substance P-saporin in rats. Neurosci. Lett. 230, 97–100.
Mantyh, P. W., Rogers, S. D., Honore, P., Allen, B. J., Ghilardi, J. R., Li, J., et al. (1997) Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science 278, 275–279.
Shiosaka, S. (1992) Attempts to make models for Alzheimer’s disease. Neurosci. Res. 13, 237–255.
DiStefano, P. S., Schweitzer, J. B., Taniuchi, M., and Johnson, E. M., Jr. (1985) Selective destruction of nerve growth factor receptor-bearing cells in vitro using a hybrid toxin composed of ricin A chain and a monoclonal antibody against the nerve growth factor receptor. J. Cell Biol. 101, 1107–1114.
Schweitzer, J. B. (1987) Nerve growth factor receptor-mediated transport from cerebrospinal fluid to basal forebrain neurons. Brain Res. 423, 309–317.
Schweitzer, J. B. (1989) Nerve growth factor receptor-mediated transport from CSF labels cholinergic neurons: direct demonstration by a double-labeling study. Brain Res. 490, 390–396.
Thorpe, P. E., Brown, A. N. F., Bremner, J. A. G., Foxwell, B. M. J., and Stirpe, F. (1985) An immunotoxin composed of monoclonal anti-Thy 1.1 antibody and a ribosome-inactivating protein from Saponaria officinalis: potent antitumor effects in vitro and in vivo. J. Natl. Cancer Inst. 75, 151–159.
Wiley, R. G. and Lappi, D. A. (1993) Preparation of anti-neuronal immunotoxins for selective neural immunolesioning. Neurosci. Protocols(93-0202), 1–11.
Heckers, S., Ohtake, T., Wiley, R. G., Lappi, D. A., Geula, C., and Mesulam, M. M. (1994) Complete and selective cholinergic denervation of rat neocortex and hippocampus but not amygdala by an immunotoxin against the p75 NGF receptor. J. Neurosci. 14, 1271–1289.
Greeson, D. M., Moix, L., Meier, M., Armstrong, D. M., and Wiley, R. G. (1992) A continuing signal maintains NGF receptor expression in hypoglossal motor neurons after crush injury. Brain Res. 594, 351–355.
Lee, M. G., Chrobak, J. J., Sik, A., Wiley, R. G., and Buzsáki, G. (1994) Hippoc-ampal theta activity following selective lesion of the septal cholinergic system. Neuroscience 62, 1033–1047.
Harrison, M. B., Roberts, R. C., and Wiley, R. G. (1993) A selective lesion of striatonigral neurons decreases presynaptic binding of [3H]hemicholinium-3 to striatal interneurons. Brain Res. 630, 169–177.
Book, A. A., Wiley, R. G., and Schweitzer, J. B. (1995) 192 IgG-saporin. 2. Neuropathology in the rat brain. Acta Neuropathol. (Berl.) 89, 519–526.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Humana Press Inc.
About this protocol
Cite this protocol
Wiley, R.G. (2001). Toxin-Induced Death of Neurotrophin-Sensitive Neurons. In: Rush, R.A. (eds) Neurotrophin Protocols. Methods in Molecular Biology™, vol 169. Humana Press. https://doi.org/10.1385/1-59259-060-8:217
Download citation
DOI: https://doi.org/10.1385/1-59259-060-8:217
Publisher Name: Humana Press
Print ISBN: 978-0-89603-699-4
Online ISBN: 978-1-59259-060-5
eBook Packages: Springer Protocols