Skip to main content
Log in

Large-Scale Analysis of Gene Expression in Epilepsy Research: Is Synthesis Already Possible?

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

DNA microarrays are now popular tools for large-scale studies of gene expression in the brain in both physiologic and pathologic conditions. Here, we review the few available papers describing the use of microarrays in experiments relevant to temporal lobe epilepsy. Review of the data indicates that products of genes regulated during epileptic processes belong to a variety of functional classes, including signal transduction, transcription regulation, protein synthesis and degradation, basic metabolism, and structural proteins. There is surprisingly little overlap in gene lists from different studies. This might be related to the limited sensitivity of microarrays or to differences in the experimental setup, such as the use of different animal models, time points, and microarrays. Despite obvious problems with interpretation of the vast amount of information derived from microarray experiments, these data are potentially excellent tools for creating new hypotheses about events occurring during circuitry reorganization in the brain that results in lowered seizure threshold and epilepsy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barlow, C. and Lockhart, D. J. 2002. DNA arrays and neurobiology—what's new and what's next? Curr. Opin. Neurobiol. 12:554–61.

    PubMed  Google Scholar 

  2. Mody, M., Cao, Y., Cui, Z., Tay, K. Y., Shyong, A., Shimizu, E., Pham, K., Schultz, P., Welsh, D., Tsein, J. Z. 2001. Genome-wide gene expression profiles of the developing mouse hippocampus. Proc. Natl. Acad. Sci. USA 98:8862–7.

    PubMed  Google Scholar 

  3. Geschwind, D. H., Ou, J., Easterday, M. C., Dougherty, J. D., Jackson, R. L., Chen, Z., Antoine, H., Terskikh, A., Weissman, I. L., Nelson, S. F., Kornblum, H. I. 2001. A genetic analysis of neural progenitor differentiation. Neuron 29:325–39.

    PubMed  Google Scholar 

  4. Lee, C. K., Weindruch, R., and Prolla, T. A. 2000. Gene-expression profile of the ageing brain in mice. Nat. Genet. 25:294–7.

    PubMed  Google Scholar 

  5. Jiang, C. H., Tsien, J. Z., Schultz, P. G., and Hu, Y. 2001. The effects of aging on gene expression in the hypothalamus and cortex of mice. Proc. Natl. Acad. Sci. USA 98:1930–4.

    PubMed  Google Scholar 

  6. Dent, G. W., O'Dell, D. M., and Eberwine, J. H. 2001. Gene expression profiling in the amygdala: an approach to examine the molecular substrates of mammalian behavior. Physiol. Behav. 73:841–7.

    PubMed  Google Scholar 

  7. Sandberg, R., Yasuda, R., Pankratz, D. G., Carter, T. A., Del Rio, J. A., Wodicka, L., Mayford, M., Lockhart, D. J., Barlow, C. 2000. Regional and strain-specific gene expression mapping in the adult mouse brain. Proc. Natl. Acad. Sci. USA 97:11038–43.

    PubMed  Google Scholar 

  8. Zirlinger, M., Kreiman, G., and Anderson, D. J. 2001. Amygdala-enriched genes identified by microarray technology are restricted to specific amygdaloid subnuclei. Proc. Natl. Acad. Sci. USA 98:5270–5.

    PubMed  Google Scholar 

  9. Zhao, X., Lein, E. S., He, A., Smith, S. C., Aston, C., and Gage, F. H. 2001. Transcriptional profiling reveals strict boundaries between hippocampal subregions. J. Comp. Neurol. 441:187–96.

    PubMed  Google Scholar 

  10. Kamme, F., Salunga, R., Yu, J., Tran, D. T., Zhu, J., Luo, L., Bittner, A., Guo, H. Q., Miller, N., Wan, J., Erlander, M. 2003. Single-cell microarray analysis in hippocampus CA1: demonstration and validation of cellular heterogeneity. J. Neurosci. 23:3607–15.

    PubMed  Google Scholar 

  11. Ginsberg, S. D., Hemby, S. E., Lee, V. M., Eberwine, J. H., and Trojanowski, J. Q. 2000. Expression profile of transcripts in Alzheimer's disease tangle-bearing CA1 neurons. Ann. Neurol. 48:77–87.

    PubMed  Google Scholar 

  12. Whitney, L. W., Becker, K. G., Tresser, N. J., Caballero-Ramos, C. I., Munson, P. J., Prabhu, V. V., Trent, J. M., McFarland, H. F., Biddison, W. E. 1999. Analysis of gene expression in mutiple sclerosis lesions using cDNA microarrays. Ann. Neurol. 46:425–8.

    PubMed  Google Scholar 

  13. Lock, C., Hermans, G., Pedotti, R., Brendolan, A., Schadt, E., Garren, H., Langer-Gould, A., Strober, S., Cannella, B., Allard, J., Klonowski, P., Austin, A., Lad, N., Kaminski, N., Galli, S. J., Oksenberg, J. R., Raine, C. S., Heller, R., Steinman, L. 2002. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 8:500–8.

    PubMed  Google Scholar 

  14. Hakak, Y., Walker, J. R., Li, C., Wong, W. H., Davis, K. L., Buxbaum, J. D., Haroutunian, V., Fienberg, A. A. 2001. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. USA 98:4746–51.

    PubMed  Google Scholar 

  15. Mirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., and Levitt, P. 2000. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 28:53–67.

    PubMed  Google Scholar 

  16. Matzilevich, D. A., Rall, J. M., Moore, A. N., Grill, R. J., and Dash, P. K. 2002. High-density microarray analysis of hippocampal gene expression following experimental brain injury. J. Neurosci. Res. 67:646–63.

    PubMed  Google Scholar 

  17. Cavallaro, S., D'Agata, V., Manickam, P., Dufour, F., and Alkon, D. L. 2002. Memory-specific temporal profiles of gene expression in the hippocampus. Proc. Natl. Acad. Sci. USA 99:16279–84.

    PubMed  Google Scholar 

  18. Ressler, K. J., Paschall, G., Zhou, X. L., and Davis, M. 2002. Regulation of synaptic plasticity genes during consolidation of fear conditioning. J. Neurosci. 22:7892–902.

    PubMed  Google Scholar 

  19. Crino, P. B., Duhaime, A. C., Baltuch, G., and White, R. 2000. Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia. Neurology 56:906–13.

    Google Scholar 

  20. Shilling, P. D. and Kelsoe, J. R. 2002. Functional genomics approaches to understanding brain disorders. Pharmacogenomics 3:31–45.

    PubMed  Google Scholar 

  21. Porter, R. J. 1993. A textbook of epilepsy. Churchill Livingstone, Oxford, UK.

    Google Scholar 

  22. Hauser, W. A. 1997. Insidence and prevalence. Pages 47–57, in Engel, J. Jr. Pedley, T. A., (eds.), Epilepsy: a comprehensive textbook. Lippincott-Raven Publishers, Philadelphia.

    Google Scholar 

  23. Pitkanen, A., and Sutula, T. P. 2002. Is the epilepsy a progressive disorder? Prospects for new therapeutic approaches in temporal-lobe epilepsy. Lancet Neurology 1:173–181.

    PubMed  Google Scholar 

  24. Nedivi, E., Hevroni, D., Naot, D., Israeli, D., and Citri, Y. 1993. Numerous candidate plasticity-related genes revealed by differential cDNA cloning. Nature 363:718–22.

    PubMed  Google Scholar 

  25. Zagulska-Szymczak, S., Filipkowski, R. K., and Kaczmarek, L. 2001. Kainate-induced genes in the hippocampus: lessons from expression patterns. Neurochem Int. 38:485–501.

    PubMed  Google Scholar 

  26. Jin, K., Mao, X. O., Eshoo, M. W., Nagayama, T., Minami, M., Simon, R. P., Greenberg, D. A. 2001 Microarray analysis of hippocampal gene expression in global cerebral ischemia. Ann. Neurol. 50:93–103.

    PubMed  Google Scholar 

  27. Morrison, B. 3rd, Eberwine, J. H., Meaney, D. F., and McIntosh, T. K. 2000. Traumatic injury induces differential expression of cell death genes in organotypic brain slice cultures determined by complementary DNA array hybridization. Neuroscience 96:131–139.

    PubMed  Google Scholar 

  28. Liu, P. K., Grossman, R. G., Hsu, C. Y., and Robertson, C. S. 2001. Ischemic injury and faulty gene transcripts in the brain. Trends Neurosci. 24:581–588.

    PubMed  Google Scholar 

  29. Read, S. J., Parsons, A. A., Harrison, D. C., Philpott, K., Kabnick, K., O'Brien, S., Clark, S., Brawner, M., Bates, S., Gloger, I., Legos, J. J., Barone, F. C. 2000. Stroke genomics: approaches to identify, validate, and understand ischemic stroke gene expression. J. Cereb. Blood Flow. Metab. 21:755–758.

    Google Scholar 

  30. White, H. S. 2002 Animal models of epileptogenesis. Neurology 59(9 Suppl 5):S7–S14.

    Google Scholar 

  31. Tang, Y., Lu, A., Aronow, B. J., Wagner, K. R., and Sharp, F. R. 2002. Genomic responses of the brain to ischemic stroke, intracerebral haemorrhage, kainate seizures, hypoglycemia, and hypoxia. Eur. J. Neurosci. 15:1937–52.

    PubMed  Google Scholar 

  32. Lukasiuk, K., Kontula, L., and Pitkanen, A. 2003 cDNA profiling of epileptogenesis in the rat brain. Eur. J. Neurosci. 17:271–9.

    PubMed  Google Scholar 

  33. Nissinen, J., Halonen, T., Koivisto, E., and Pitkanen, A. 2000. A new model of chronic temporal lobe epilepsy induced by electrical stimulation of the amygdala in rat. Epilepsy Res. 38:177–205.

    PubMed  Google Scholar 

  34. Long, Y., Zou, L., Liu, H., Lu, H., Yuan, X., Robertson, C. S., Yang, K. 2003. Altered expression of randomly selected genes in mouse hippocampus after traumatic brain injury. J. Neurosci. Res. 71:710–20.

    PubMed  Google Scholar 

  35. Elliott, R. C., Miles, M. F., and Lowenstein, D. H. 2003. Overlapping microarray profiles of dentate gyrus gene expression during development-and epilepsy-associated neurogenesis and axon outgrowth. J. Neurosci. 23:2218–27.

    PubMed  Google Scholar 

  36. Hendriksen, H., Datson, N. A., Ghijsen, W. E., van Vliet, E. A., da Silva, F. H., Gorter, J. A., Vreugdenhil, E. 2001. Altered hippocampal gene expression prior to the onset of spontaneous seizures in the rat post-status epilepticus model. Eur. J. Neurosci. 14:1475–84.

    PubMed  Google Scholar 

  37. Becker, A. J., Chen, J., Paus, S., Normann, S., Beck, H., Elger, C. E., Wiestler, O. D., Blumcke, I. 2002. Transcriptional profiling in human epilepsy: expression array and single cell real-time qRT-PCR analysis reveal distinct cellular gene regulation. Neuroreport 13:1327–33.

    PubMed  Google Scholar 

  38. Sandberg, R., Yasuda, R., Pankratz, D. G., Carter, T. A., Del Rio, J. A., Wodicka, L., Mayford, M., Lockhart, D. J., Barlow, C.2000. Regional and strain-specific gene expression mapping in the adult mouse brain. Proc. Natl. Acad. Sci. USA 97:11038–43.

    PubMed  Google Scholar 

  39. French, P. J., O'Connor, V., Voss, K., Stean, T., Hunt, S. P., and Bliss, T. V. 2001. Seizure-induced gene expression in area CA1 of the mouse hippocampus. Eur. J. Neurosci. 14:2037–41.

    PubMed  Google Scholar 

  40. Evans, S. J., Datson, N. A., Kabbaj, M., Thompson, R. C., Vreugdenhil, E., De Kloet, E. R., Watson, S. J., Akil, H. 2002. Evaluation of Affymetrix Gene Chip sensitivity in rat hippocampal tissue using SAGE analysis. Serial analysis of gene expression. Eur. J. Neurosci. 16:409–13.

    PubMed  Google Scholar 

  41. Doherty, J., Ciliax, N., Zhang, S., Borges, K., and Dingledine, R. 2001. Spatial and temporal patterns of gene expression during epileptogenesis in the mouse hippocampus. Epilepsia 42 (Suppl 7):111.

    Google Scholar 

  42. Lukasiuk, K., Pirttila, T. J., and Pitkanen, A. 2002. Upregulation of cystatin C expression in the rat hippocampus during epileptogenesis in the amygdala stimulation model of temporal lobe epilepsy. Epilepsia 43 (Suppl 5):137–45.

    PubMed  Google Scholar 

  43. Aronica, E., van Vliet, E. A., Hendriksen, E., Troost, D., Lopes da Silva, F. H., and Gorter, J. A. 2001. Cystatin C, a cysteine protease inhibitor, is persistently up-regulated in neurons and glia in a rat model for mesial temporal lobe epilepsy. Eur. J. Neurosci. 14:1485–91.

    PubMed  Google Scholar 

  44. Potschka, H., Krupp, E., Ebert, U., Gumbel, C., Leichtlein, C., Lorch, B., Pickert, A., Kramps, S., Young, K., Grune, U., Keller, A., Welschof, M., Vogt, G., Xiao, B., Worley, P. F., Loscher, W., Hiemisch 2002. Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Eur. J. Neurosci. 16:2157–65.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lukasiuk, K., Pitkänen, A. Large-Scale Analysis of Gene Expression in Epilepsy Research: Is Synthesis Already Possible?. Neurochem Res 29, 1169–1178 (2004). https://doi.org/10.1023/B:NERE.0000023604.91584.6c

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000023604.91584.6c

Navigation