Biochemical Approaches to Studying Neurotoxicity

Stephanie Padilla1

1 U.S. Environmental Protection Agency, Research Triangle Park, North Carolina
Publication Name:  Current Protocols in Toxicology
Unit Number:  Unit 12.1
DOI:  10.1002/0471140856.tx1201s03
Online Posting Date:  May, 2001
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

This overview provides an introduction to biochemical analysis of toxicant effects on the nervous system. It includes a brief discussion of the salient features of the nervous system and a review of the various approaches used to detect and identify neurotoxicants and their modes of action.

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Neurotransmitter Dynamics
  • Axonal Transport
  • Identification of Stressed or Damaged Cells
  • Markers
  • Sensitive Subpopulations
  • Emerging Approaches
  • Literature Cited
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
   Abou‐Donia, M.B., Lapadula, D.M., and Carrington, C.D. 1988. Biochemical methods for assessment of neurotoxicity. In Perspectives in Basic and Applied Toxicology (B. Ballantyne, ed.) pp.1‐30. Wright Publishing, London.
   Bergamaschi, E., Mutti, A., Cavazzini, S., Vettori, M.V., Renzulli, F.S., and Franchini, I. 1996. Peripheral markers of neurochemical effects among styrene‐exposed workers. Neurotoxicology 17:753‐759.
   Bergmark, E., Calleman, C.J., He, F., and Costa, L.G. 1993. Determination of hemoglobin adducts in humans occupationally exposed to acrylamide. Toxicol. Appl. pharmacol. 20:45‐54.
   Bondy, S.C. 1986. The biochemical evaluation of neurotoxic damage. Fundam. Appl. Toxicol. 6:208‐216.
   Boyd, C.A., Weiler, M.H., and Porter, W.P. 1990. Behavioral and neurochemical changes associated with chronic exposure to low‐level concentration of pesticide mixtures. J. Toxicol. Environ. Health. 30:209‐221.
   Brat, D.J. and Brimijoin, S. 1992. A paradigm for examining toxicant effects on viability, structure and axonal transport of neurons in culture. Mol. Neurobiol. 6:125‐135.
   Brodie, M.E., Opacka‐Juffry, J., Peterson, D.W., and Brown, A.W. 1990. Neurochemical changes in hippocampal and caudate dialysates associated with early trimethyltin neurotoxicity in rats. Neurotoxicology 11:35‐46.
   Brooks, W.M., Sabet, A., Sibbitt, W.L., Jr., Barker, P.B., van Zijl, P.C., Duyn, J.H., and Moonen, C.T. 1997. Neurochemistry of brain lesions determined by spectroscopic imaging in systemic lupus erythematosus. J. Rheumatol. 24:2323‐2329
   Chandler, L.J., Newsom, H., Sumners, C., and Crews, F. 1993. Chronic ethanol exposure potentiates NMDA excitotoxicity in cerebral cortical neurons. J. Neurochem. 60:1578‐1581
   Chen, H.H., Ma, T., Paul, I.A., Spencer, J.L., and Ho, I.K. 1997. Developmental lead exposure and two‐way active avoidance training alter the distribution of protein kinase C activity in the rat hippocampus. Neurochem. Res. 22:1119‐1125
   Clarke, C.H. and Sickles, D.W. 1996. Decreased GAP‐43 accumulation in neurite tips of cultured hippocampal neurons by acrylamide. Neurotoxicology 17:397‐406.
   Costa, L.G. 1988. Interactions of neurotoxicants with neurotransmitter systems. Toxicology 49:359‐366.
   Costa, L.G. 1992. Effects of neurotoxicants on brain neurochemistry. In Neurotoxicology (H. Tilson and C. Mitchell, eds.) Raven Press, New York.
   Costa, L.G. 1994. Signal transduction mechanisms in developmental neurotoxicity: The phosphoinositide pathway. Neurotoxicology 15:19‐27.
   Costa, L.G., Marinovich, M., Galli, C.L. 1988. Receptor binding techniques in neurotoxicology. In Recent Advances in Nervous System Toxicology (C.L. Galli, L. Manzo, and P.S. Spencer, eds.) pp. 307‐349. Plenum Press, New York.
   Costa, L.G., Deng, H., Calleman, C.J., and Bergmark, E. 1995. Evaluation of the neurotoxicity of glycidamide, an epoxide metabolite of acrylamide: Behavioral, neurochemical, and morphological studies. Toxicology 98:151‐161.
   Crofton, K.M., Padilla, S., Tilson, H.A., Anthony, D.C., Raymer, J.H., and MacPhail, R.C. 1996. The impact of dose rate on the neurotoxicity of acrylamide: The interaction of administered dose, target tissue concentrations, tissue damage, and functional effects. Toxicol. Appl. Pharmacol. 139:163‐176.
   Dawson, V.L. and Dawson, T.M. 1996. Nitric oxide neurotoxicity. J. Chem. Neuroanat. 10:179‐190.
   Evans, J.E., Miller, M.L., Andringa, A., and Hastings, L. 1995. Behavioral, histological and neurochemical effects of nickel (II) on the rat olfactory system. Toxicol. Appl. Pharmacol. 130:209‐220.
   Fredricksson, A., Fredriksson, M., and Eriksson, P. 1993. Neonatal exposure to paraquat of MPTP induces permanent changes in striatum dopamine and behavior in mice. Toxicol. Appl. Pharmacol 122:258‐264
   Goldstein, G.W. 1993. Evidence that lead acts as a calcium substitute in second messenger metabolism. Neurotoxicology 14:97‐101.
   Huff, R.A., Corcoran, J.J., Anderson, J.K., and Abou‐Donia, M.B. 1994. Chlorpyrifos oxon binds directly to muscarinic receptors and inhibits cAMP accumulation in rat striatum. J. Pharmacol. Exp. Ther. 269:329‐335.
   Huxlin, K.R. and Bennett, M.R. 1995. NADPH diaphorase expression in the rat retina after axontomy—a supportive role for nitric oxide. Euro. J. Neurosci. 7:2226‐2239.
   Kanthasamy, A.G., Borowitz, J.L., Pavlakovic, G., and Isom, G.E. 1994. Dopamine neurotoxicity of cyanide: Neurochemical, histological, and behavioral characterization. Toxicol. Appl. Pharmacol. 126:156‐163.
   Kikuchi, S. and Kim, S.U. 1993. Glutamate neurotoxicity in mesencephalic dopaminergic neurons in culture. J. Neurosci. Res. 36:558‐569.
   Komulainen, H., Keranen, A., and Saano, V. 1995. Methylmercury modulates GABA‐A receptor complex differently in rat cortical and cerebellar membranes in vitro. Neurochem. Res. 20:659‐662.
   Lam, H.R., Ladefoged, O., Ostergaard, G., Lund, S.P., and Simonsen, L. 1996. Four weeks' inhalation exposure of rats to p‐cymene affects regional and synaptosomal neurochemistry. Pharmacol. Toxicol. 79:225‐230.
   Layton, M.E., Wagner, J.K., Samson, F.E., and Pazdernik, T.L. 1997. Redox changes in perfusates following intracerebral penetration of microdialysis probes. Neurochem. Res. 22:735‐741.
   Li, W.F., Matthews, C., Disteche, C.M., Costa, L.G., and Furlong, C.E. 1997. Paraoxonase (PON1) gene in mice: Sequencing, chromosomal localization and developmental expression. Pharmacogenetics 7:137‐144.
   Liu, J. and Pope, C.N. 1996. Effects of chlorpyrifos on high‐affinity choline uptake and [3H]hemicholinium‐3 binding in rat brain. Fundam. Appl. Toxicol. 34:84‐90.
   Maiese, K., Boniece, I.R., Skurat, K., and Wagner, J.A. 1993. Protein kinases modulate the sensitivity of hippocampal neurons to nitric oxide toxicity and anoxia. J. Neurosci. Res. 36:77‐87.
   Manzo, L., Artigas, F., Martinez, E., Mutti, A., Bergamaschi, E., Nicotera, P., Tonini, M., Candura, S.M., Ray, D.E., and Costa, L.G. 1996. Biochemical markers of neurotoxicity. A review of mechanistic studies and applications. Hum. Exp. Toxicol. 15:S20‐35.
   Morse, D.C., Plug, A., Wesseling, W., van den Berg, K.J., and Brouwer, A. 1996. Persistent alterations in regional brain glial fibrillary acidic protein and synaptophysin levels following pre‐ and postnatal polychlorinated biphenyl exposure. Toxicol. Appl. Pharmacol. 139:252‐261.
   Mortensen, S.R., Chanda, S.M., Hooper, M.J., and Padilla, S. 1996. Maturational differences in chlorpyrifos‐oxonase activity may contribute to age‐related sensitivity to chlorpyrifos. Biochem. Toxicol. 11:279‐287.
   Nagata, K., Huang, C.S., Song, J.H., and Narahashi, T. 1997. Lead modulation of the neuronal nicotinic acetylcholine receptor in PC12 cells. Brain Res. 754:21‐27.
   O'Callaghan, J.P. 1992. Assessment of neurotoxicity using assays of neuron‐ and glia‐localized proteins: Chronology and critique. In Neurotoxicology (H. Tilson and C. Mitchell, eds.) pp. 83‐100. Raven Press, New York.
   Ochs, S. and Brimijoin, W.S. 1993. Axonal Transport. In Peripheral Neuropathy, 3rd ed. (P.J. Dyck and P.K. Thomas, eds.) pp. 331‐360. W.B. Saunders, Philadelphia.
   Opanashuk, L.A. and Finkelstein, J.N. 1995. Relationship of lead‐induced proteins to stress response proteins in astroglial cells. J. Neurosci. Res. 42:623‐632.
   Oppenheim, R.W. 1996. The concept of uptake and retrograde transport of neurotrophic molecules during development: History and present status. Neurochem. Res. 21:769‐777.
   Pahwa, R. and Kalra, J. 1993. A critical review of the neurotoxicity of styrene in humans. Vet. Hum. Toxicol. 35:516‐520.
   Richter, J.A., Brennerman, M.G., Dlouhy, S.R., and Ghetti, B. 1995. Dopaminergic parameters in the striatum and substantia nigra of seven strains of mice: Higher density in striatum of CAST compared to BALB mice. Neurochem. Res. 20:395‐400.
   Rising, L., Vitarella, D., Kimelberg, H.K., and Aschner, M. 1995. Metallothionein induction in neonatal rat primary astrocyte cultures protects against methylmercury cytotoxicity. J. Neurochem. 65:1562‐1568.
   Roberson, M.D., Toews, A.D., Bouldin, T.W., Weaver, J., Goines, N.D., and Morell, P. 1995. NGFR‐mRNA expression in sciatic nerve: A sensitive indicator of early stages of axonopathy. Mol. Brain Res. 28:231‐238.
   Rocha, E.S., Swanson, K.L., Aracava, Y., Goolsby, J.E., Maelicke, A., and Albuquerque, E.X. 1996. Paraoxon: Cholinesterase‐independent stimulation of transmitter release and selective block of ligand‐gated ion channels in cultured hippocampal neurons. J. Pharmacol. Exp. Ther. 278:1175‐1187.
   Sickles, D.W., Brady, S.T., Testino, A., Friedman, M.A., and Wrenn, R.W. 1996. Direct effects of the neurotoxicant acrylamide on kinesin‐based microtubule motility. J. Neurosci. Res. 46:7‐17.
   Sorg, B.A., Willis, J.R., Nowatka, T.C., Ulibarri, C., See, R.E., and Westbert, H.H. 1996. Proposed animal neurosensitization model for multiple chemical sensitivity in studies with formalin. Toxicology 111:135‐145.
   Strong, M.J., Garruto, R.M., Joshi, J.G., Mundy, W.R., and Shafer, T.J. 1996. Can the mechanisms of aluminum neurotoxicity be integrated into a unified scheme? J. Toxicol. Environ. Health 48:599‐613.
   Tandon, P., Padilla, S., Barone, S., Jr., Pope, C.N., and Tilson, H.A. 1994. Fenthion produces a persistent decrease in muscarinic receptor function in the adult rat retina. Toxicol. Appl. Pharmacol. 125:271‐280.
   Toggas, S.M., Krady, J.K., and Billingsley, M.L. 1992. Molecular neurotoxicology of trimethyltin: Identification of stannin, a novel protein expressed in trimethyltin‐sensitive cells. Mol. Pharmacol. 42:44‐56.
   Tonner, L.E., Katz, D.I., and Heiman, A.S. 1997. The acute effect of lead acetate on glucocorticoid receptor binding in C6 glioma cells. Toxicology 116:109‐122.
   Tymianski, M. 1996. Cytosolic calcium concentrations and cell death in vitro. Adv. Neurol. 71:85‐105
   Verity, M.A. 1992. Ca(2+)‐dependent processes as mediators of neurotoxicity. Neurotoxicology 13:139‐147.
   Ward, T.R. and Mundy, W.R. 1996. Organophosphorus compounds preferentially affect second messenger systems coupled to M2/M4 receptors in rat frontal cortex. Brain Res. Bull. 39:49‐55.
   Wu, W. and Welsh, M.J. 1996. Expression of the 25‐ kDa heat‐shock protein (HSP27) correlates with resistance to the toxicity of cadmium chloride, mercuric chloride, cis‐platinum(II)‐diammine dichloride, or sodium arsenite in mouse embryonic stem cells transfected with sense or antisense HSP27 cDNA. Toxicol. Appl. Pharmacol. 141:330‐339
   Zhang, P., Milles, B.S., Rosenzweig, S.A., and Bhat, N.R. 1996. Activation of C‐jun N‐terminal kinase/stress‐activated protein kinase in primary glial cultures. J. Neurosci. Res. 46:114‐121.
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library