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A review of gene expression patterns in the malformed brain

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Abstract

Major advances in the identification of genes expressed in malformation-associated epileptic disorders have been made. Some of these changes reflect the complex gene interactions necessary for proper neurodevelopment, whereas others suggest specific synaptic aberrations that could result in a hyperexcitable, and ultimately, epileptic condition. Here we review reported changes in gene expression associated with a malformed brain, with particular emphasis on how these changes provide clues to seizure genesis.

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References

  1. Chevassus-au-Louis, N., Baraban, S. C., Gracias, G.-L., and Ben-Ari, Y. (1999) Cortical malformations and epilepsy: new insights from animal models. Epilepsia 40, 811–821.

    Article  PubMed  CAS  Google Scholar 

  2. Schwartzkroin, P. A. and Walsh, C. (2000) Cortical malformations and epilepsy. Mental Retardation Dev. Disabilities 6, 268–280.

    Article  CAS  Google Scholar 

  3. Palmini, A. (2000) Disorders of cortical development. Curr. Opin. Neurol. 13, 183–92.

    Article  PubMed  CAS  Google Scholar 

  4. Kuzniecky, R. I. and Barkovich, A. J. (2001) Malformations of cortical development and epilepsy. Brain Dev. 23, 2–11.

    Article  PubMed  CAS  Google Scholar 

  5. Palmini, A., Gambardella, A., Andermann, F., Dubeau, F., da Costa, J. C., Olivier, A., et al. (1995) Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results. Ann. Neurol. 37, 476–87.

    Article  PubMed  CAS  Google Scholar 

  6. Ohtsuka, Y., Yoshinaga, H., and Kobayashi, K. (2000) Refractory childhood epilepsy and factors related to refractoriness. Epilepsia 41, 14–7.

    Article  PubMed  Google Scholar 

  7. Yamanouchi, H., Zhang, W., Jay, V., and Becker, L. E. (1996) Enhanced expression of microtubule-associated protein 2 in large neurons of cortical dysplasia. Ann. Neurol. 39, 57–61.

    Article  PubMed  CAS  Google Scholar 

  8. Duong, T., De Rosa, M. J., Poukens, V., Vinters, H. V., and Fisher, R. S. (1994) Neuronal cytoskeletal abnormalities in human cerebral cortical dysplasia. Acta Neuropathol 87, 493–503.

    PubMed  CAS  Google Scholar 

  9. Taylor, J. P., Sater, R., French, J., Baltuch, G., and Crino, P. B. (2001) Transcription of intermediate filament genes is enhanced in focal cortical dysplasia. Acta Neuropathol. (Berl) 102, 141–148.

    CAS  Google Scholar 

  10. Baraban, S. C., Wenzel, H. J., Hochman, D. W., and Schwartzkroin, P. A. (2000) Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero. Epilepsy Res. 39, 87–102.

    Article  PubMed  CAS  Google Scholar 

  11. Hoffman, J. R., Boyne, L. J., Levitt, P., and Fischer, I. (1996) Short exposure to methylazoxymethanol causes a long-term inhibition of axonal outgrowth from cultured embryonic rat hippocampal neurons. J. Neurosci Res. 46, 349–359.

    Article  PubMed  CAS  Google Scholar 

  12. Crino, P. B., Trojanowski, J. Q., and Eberwine, J. (1997) Internexin, MAP1B, and nestin in cortical dysplasia as markers of developmental maturity. Acta Neuropathol. (Berl) 93, 619–27.

    Article  CAS  Google Scholar 

  13. Duggal, N., Iskander, S., and Hammond, R. R. (2001) Nestin expression in cortical dysplasia. J. Neurosurg. 95, 459–465.

    Article  PubMed  CAS  Google Scholar 

  14. Sherman, G. F., Stone, J. S., Press, D. M., Rosen, G. D., and Galaburda, A. M. (1990) Abnormal architecture and connections disclosed by neurofilament staining in the cerebral cortex of autoimmune mice. Brain Res 529, 202–207.

    Article  PubMed  CAS  Google Scholar 

  15. Fox, J. W., Lamperti, E. D., Eksioglu, Y. Z., Hong, S. E., Feng, Y., Graham, D. A., et al. (1998) Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia. Neuron 21, 1315–1325.

    Article  PubMed  CAS  Google Scholar 

  16. Goldstein, L. S. and Yang, Z. (2000) Microtubule-based transport systems in neurons: the roles of kinesins and dyneins. Annu. Rev. Neurosci. 23, 39–71.

    Article  PubMed  CAS  Google Scholar 

  17. Vinters, H. V., Park, S. H., Johnson, M. W., Mischel, P. S., Catania, M., and Kerfoot, C. (1999) Cortical dysplasia, genetic abnormalities and neurocutaneous syndromes. Dev. Neurosci. 21, 248–59.

    Article  PubMed  CAS  Google Scholar 

  18. Mizuguchi, M. and Takashima, S. (2001) Neuropathology of tuberous sclerosis. Brain Dev. 23, 508–15.

    Article  PubMed  CAS  Google Scholar 

  19. Gao, X. and Pan, D. (2001) TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15, 1383–92.

    Article  PubMed  CAS  Google Scholar 

  20. Potter, C. J., Huang, H., and Xu, T. (2001) Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357–68.

    Article  PubMed  CAS  Google Scholar 

  21. Cardoso, C., Leventer, R. J., Dowling, J. J., Ward, H. L., Chung, J., Petras, K. S., et al. (2002) Clinical and molecular basis of classical lissencephaly: mutations in the LIS1 gene (PAFAH1B1). Hum. Mutat. 19, 4–15.

    Article  PubMed  CAS  Google Scholar 

  22. Feng, Y. and Walsh, C. A. (2001) Protein-protein interactions, cytoskeletal regulation and neuronal migration. Nat. Rev. Neurosci. 2, 408–416.

    Article  PubMed  CAS  Google Scholar 

  23. Allen, K. M. and Walsh, C. A. (1999) Genes that regulate neuronal migration in the cerebral cortex. Epilepsy Res. 36, 143–154.

    Article  PubMed  CAS  Google Scholar 

  24. Lambert de Rouvroit, C. and Goffinet, A. M. (2001) Neuronal migration. Mech. Dev. 105, 47–56.

    Article  PubMed  CAS  Google Scholar 

  25. Hong, S. E., Shugart, Y. Y., Huang, D. T., Shahwan, S. A., Grant, P. E., Hourihane, J. O., et al. (2000) Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations. Nat. Genet. 26, 93–96.

    Article  PubMed  CAS  Google Scholar 

  26. Wenzel, H. J., Robbins, C. A., Tsai, L. H., and Schwartzkroin, P. A. (2001) Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures. J. Neurosci. 21, 983–998.

    PubMed  CAS  Google Scholar 

  27. Houser, C. R. (1990) Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy. Brain Res. 535, 195–204.

    Article  PubMed  CAS  Google Scholar 

  28. Harrison, T. R. and Fauci, A. S. (1998) Harrison’s principles of internal medicine, 14th Ed. McGraw-Hill Health Professions Division, New York.

    Google Scholar 

  29. Ying, Z., Babb, T. L., Mikuni, N., Najm, I., Drazba, J., and Bingaman, W. (1999) Selective coexpression of NMDAR2A/B and NMDAR1 subunit proteins in dysplastic neurons of human epileptic cortex. Exp. Neurol. 159, 409–418.

    Article  PubMed  CAS  Google Scholar 

  30. Najm, I. M., Ying, Z., Babb, T., Mohamed, A., Hadam, J., LaPresto, E., et al. (2000) Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia. Epilepsia 41, 971–976.

    Article  PubMed  CAS  Google Scholar 

  31. Crino, P. B., Duhaime, A. C., Baltuch, G., and White, R. (2001) Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia. Neurology 56, 906–913.

    PubMed  CAS  Google Scholar 

  32. Hablitz, J. J. and DeFazio, R. A. (2000) Altered receptor subunit expression in rat neocortical malformations. Epilepsia 41, S82-S85.

    Article  PubMed  Google Scholar 

  33. Rafiki, A., Chevassus-au-Louis, N., Ben-Ari, Y., Khrestchatisky, M., and Represa, A. (1998) Glutamate receptors in dysplasic cortex: an in situ hybridization and immunohistochemistry study in rats with prenatal treatment with methylazoxymethanol. Brain Res. 782, 142–152.

    Article  CAS  Google Scholar 

  34. Yamanouchi, H., Mizuguchi, M., Oka, A., Takashima, S., Becker, L. E., Eguchi, M., and Nakazato, Y. (2000) Enhanced GAP-43 gene expression in cortical dysplasia. Neuroreport 11, 1815–1819.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Epilepsy Research Laboratory, Box 0520, Department of Neurological Surgery & The Graduate Program in Neuroscience, University of California, 513 Parnassus Ave, 94143, San Francisco, CA

    Mercedes F. Paredes & Scott C. Baraban

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  1. Mercedes F. Paredes
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  2. Scott C. Baraban
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Correspondence to Scott C. Baraban.

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Paredes, M.F., Baraban, S.C. A review of gene expression patterns in the malformed brain. Mol Neurobiol 26, 109–116 (2002). https://doi.org/10.1385/MN:26:1:109

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  • DOI: https://doi.org/10.1385/MN:26:1:109

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