Behavior Genetics

, Volume 33, Issue 5, pp 537–548 | Cite as

Large-Scale Gene Expression Profiling of Discrete Brain Regions: Potential, Limitations, and Application in Genetics of Aggressive Behavior

  • Dorine E. M. Feldker
  • E. Ronald de Kloet
  • Menno R. Kruk
  • Nicole A. Datson

Abstract

Many behavioral geneticists are interested in unraveling the molecular mechanisms underlying aggressive behavior. So far, most scientists have based their search for aggression-related genes on a preliminary functional hypothesis. Large-scale gene expression profiling techniques, such as serial analysis of gene expression (SAGE) and DNA microarrays, now enable the screening of expression levels of thousands of genes simultaneously, allowing the identification of new candidate aggression-related genes expressed in brain and thus the generation of new hypotheses. However, expression profiling in the brain is challenging, as brain is a complex heterogeneous tissue where large numbers of genes are expressed and relatively small changes in gene expression occur. In this special issue, we focus on the principles of SAGE and DNA microarrays, as well as their advantages and disadvantages and application to analysis in brain tissue in order to identify aggression-related genes.

Serial analysis of gene expression SAGE DNA microarray hippocampus brain 

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References

  1. Benus, R. F., Bohus, B., Koolhaas, J. M., and van Oortmerssen, G. (1989). Behavioural strategies of aggressive and non-aggressive male mice in active shock avoidance. Behav. Process. 20: 1-12.Google Scholar
  2. Benus, R. F., den Daas, S., Koolhaas, J. M., and van Oortmerssen, G. (1990). Routine formation and flexibility in social and nonsocial behaviour of aggressive and non-aggressive male mice. Behaviour. 112: 176-193.Google Scholar
  3. Bohus, B., Benus, R. F., Fokkema, D. S., Koolhaas, J. M., Nyakas, C., van Oortmerssen, G. A., Prino, A. J., de Ruiter, A. J., Scheurink, A. J., and Steffens, A. B. (1987). Neuroendocrine states and behavioral and psychiological stress responses. Prog. Brain Res. 72: 57-70.Google Scholar
  4. Brazma, A., Hingamp, P., Quackenbush, J., Sherlock, G., Spellman, P., Stoeckert, C., Aach, J., Ansorge, W., Ball, C. A., Causton, H. C., Gaasterland, T., Glenisson, P., Holstege, F. C., Kim, I. F., Markowitz, V., Matese, J. C., Parkinson, H., Robinson, A., Sarkans, U., Schulze-Kremer, S., Stewart, J., Taylor, R., Vilo, J., and Vingron, M. (2001). Minimum information about a microarray experiment (MIAME)-toward standards for microarray data. Nat. Genet. 29: 365-371.Google Scholar
  5. Brodkin, E. S., Goforth, S. A., Keene, A. H., Fossella, J. A., and Silver, L. M. (2002). Identification of quantitative trait loci that affect aggressive behavior in mice. J. Neurosci. 22: 1165-1170.Google Scholar
  6. Chen, J. J., Rowley, J. D., and Wang, S. M. (2000). Generation of longer cDNA fragments from serial analysis of gene expression tags for gene identification. Proc. Natl. Acad. Sci. USA. 97: 349-353.Google Scholar
  7. Chrast, R., Scott, H. S., Papasavvas, M. P., Rossier, C., Antonarakis, E. S., Barras, C., Davisson, M. T., Schmidt, C., Estivill, X., Dierssen, M., Pritchard, M., and Antonarakis, S. E. (2000). The mouse brain transcriptome by SAGE: Differences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals. Genome Res. 10: 2006-2021.Google Scholar
  8. Craven, R. A., and Banks, R. E. (2001). Laser capture microdissection and proteomics: Possibilities and limitation. Proteomics. 1: 1200-1204.Google Scholar
  9. Datson, N. A., van der Perk-de Jong, J., van den Berg, M. P., De Kloet, E. R., and Vreugdenhil, E. (1999). MicroSAGE: A modified procedure for serial analysis of gene expression in limited amounts of tissue. Nucleic Acids Res. 27: 1300-1307.Google Scholar
  10. Datson, N. A., van der Perk, J., De Kloet, E. R., and Vreugdenhil, E. (2001a). Expression profile of 30,000 genes in hippocampus using SAGE. Hippocampus. 11: 430-444.Google Scholar
  11. Datson, N. A., van der Perk, J., De Kloet, E. R., and Vreugdenhil, E. (2001b). Identification of corticosteroid-responsive genes in rat hippocampus using serial analysis of gene expression. Eur. J. Neuroscience. 14: 1-17.Google Scholar
  12. Eberwine, J., Yeh, H., Miyashiro, K., Cao, Y., Nair, S., Finnell, R., Zettel, M., and Coleman, P. (1992). Analysis of gene expression in single live neurons. Proc. Natl. Acad. Sci. USA. 89: 3010-3014.Google Scholar
  13. Evans, S. J., Datson, N. A., Kabbaj, M., Thompson, R. C., Vreugdenhil, E., De Kloet, E. R., Watson, S. J., and Akil, H. (2002). Evaluation of Affymetrix Gene Chip sensitivity in rat hippocampal tissue using SAGE analysis. Eur. J. Neurosci. 16: 409-413.Google Scholar
  14. Feldker, D. E. M., Datson, N. A., Veenema, A. H., Meulmeester, E., De Kloet, E. R., and Vreugdenhil, E. (2003). Serial analysis of gene expression predicts structural differences in hippocampus of long attack latency and short attack latency mice. Eur. J. Neurosci. 17: 379-387.Google Scholar
  15. Gerlai, R. (2001). Gene targeting: Technical confounds and potential solutions in behavioral brain research. Behav. Brain Res. 125: 13-21.Google Scholar
  16. Halasz, J., Liposits, Z., Kruk, M. R., and Haller, J. (2002). Neural background of glucocorticoid dysfunction-induced abnormal aggression in rats: Involvement of fear-and stress-related structures. Eur. J. Neurosci. 15: 561-569.Google Scholar
  17. Hashimoto, S. I., Suzuki, T., Nagai, S., Yamashita, T., Toyoda, N., and Matsushima, K. (2000). Identification of genes specifically expressed in human activated and mature dendritic cells through serial analysis of gene expression. Blood. 96: 2206-2214.Google Scholar
  18. Ishii, M., Hashimoto, S., Tsutsumi, S., Wada, Y., Matsushima, K., Kodama, T., and Aburatani, H. (2000). Direct comparison of GeneChip and SAGE on the quantitative accuracy in transcript profiling analysis [in process citation]. Genomics. 68: 136-143.Google Scholar
  19. Klose, J., Nock, C., Herrmann, M., Stuhler, K., Marcus, K., Bluggel, M., Krause, E., Schalkwyk, L. C., Rastan, S., Brown, S. D., Bussow, K., Himmelbauer, H., and Lehrach, H. (2002). Genetic analysis of the mouse brain proteome. Nat. Genet. 30: 385-393.Google Scholar
  20. Korte, S. M., Meijer, O. C., De Kloet, E. R., Buwalda, B., Keijser, J., Sluyter, F., van Oortmerssen, G., and Bohus, B. (1996). Enhanced 5-HT1A receptor expression in forebrain regions of aggressive house mice. Brain Res. 736: 338-343.Google Scholar
  21. Lal, A., Lash, A. E., Altschul, S. F., Velculescu, V., Zhang, L., McLendon, R. E., Marra, M. A., Prange, C., Morin, P. J., Polyak, K., Papadopoulos, N., Vogelstein, B., Kinzler, K. W., Strausberg, R. L., and Riggins, G. J. (1999). A public database for gene expression in human cancers. Cancer Res. 59: 5403-5407.Google Scholar
  22. Lash, A. E., Tolstoshev, C. M., Wagner, L., Schuler, G. D., Strausberg, R. L., Riggins, G. J., and Altschul, S. F. (2000). SAGEmap: A public gene expression resource. Genome Res. 10: 1051-1060.Google Scholar
  23. Le Roy, I., Pothion, S., Mortaud, S., Chabert, C., Nicolas, L., Cherfouh, A., and Roubertoux, P. L. (2000). Loss of aggression, after transfer onto a C57BL/6J background, in mice carrying a targeted disruption of the neuronal nitric oxide synthase gene. Behav. Genet. 30: 367-373.Google Scholar
  24. Maxson, S. C. (1998). Homologous genes, aggression and animal models. Dev. Neuropsychol. 14: 143-156.Google Scholar
  25. Miczek, K. A., Maxson, S. C., Fish, E. W., and Faccidomo, S. (2001). Aggressive behavioral phenotypes in mice. Behav. Brain Res. 125: 167-181.Google Scholar
  26. Mikics, E., Kruk, M. R., Maller, J. Genomic and non-genomic effects of glucocorticoids on aggressive behavior in male rats. Psychoneuroendocrinology (in press).Google Scholar
  27. Nacht, M., Ferguson, A. T., Zhang, W., Petroziello, J. M., Cook, B. P., Gao, Y. H., Maguire, S., Riley, D., Coppola, G., Landes, G. M., Madden, S. L., and Sukumar, S. (1999). Combining serial analysis of gene expression and array technologies to identify genes differentially expressed in breast cancer. Cancer Res. 59: 5464-5470.Google Scholar
  28. Neilson, L., Andalibi, A., Kang, D., Coutifaris, C., Strauss, J. F., III, Stanton, J. A., and Green, D. P. (2000). Molecular phenotype of the human oocyte by PCR-SAGE. Genomics. 63: 13-24.Google Scholar
  29. Nelson, R. J., Demas, G. E., Huang, P. L., Fishman, M. C., Dawson, V. L., Dawson, T. M., and Snyder, S. H. (1995). Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. Nature. 378: 383-386.Google Scholar
  30. Nisenbaum, L. K. (2002). The ultimate chip shot: Can microarray technology deliver for neuroscience? Genes. Brain Behav. 1: 27-34.Google Scholar
  31. Peters, D. G., Kassam, A. B., Yonas, H., O'Hare, E. H., Ferrell, R. E., and Brufsky, A. M. (1999). Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite. Nucleic Acids Res. 27: e39.Google Scholar
  32. Roeling, T. A., Veening, J. G., Kruk, M. R., Peters, J. P., Vermelis, M. E., and Nieuwenhuys, R. (1994). Efferent connections of the hypothalamic “aggression area” in the rat. Neuroscience. 59: 1001-1024.Google Scholar
  33. Roubertoux, P. L., and Roy-Duflos, I. (2001). Quantitative trait locus mapping: Fishing strategy or replicable results? Behav. Genet. 31: 141-148.Google Scholar
  34. Sandberg, R., Yasuda, R., Pankratz, D. G., Carter, T. A., Del Rio, J. A., Wodicka, L., Mayford, M., Lockhart, D. J., and Barlow, C. (2000). Regional and strain-specific gene expression mapping in the adult mouse brain. Proc. Natl. Acad. Sci. USA. 97: 11038-11043.Google Scholar
  35. Sapolsky, R. M. (2001). Depression, antidepressants, and the shrinking hippocampus. Proc. Natl. Acad. Sci. USA. 98: 12320-12322.Google Scholar
  36. Schena, M. (1999). DNA microarrays: A practical approach, Oxford: Oxford University Press.Google Scholar
  37. Schena, M., Shalon, D., Davis, R. W., and Brown, P. O. (1995). Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science. 270: 467-470.Google Scholar
  38. Siegel, A., Roeling, T. A., Gregg, T. R., and Kruk, M. R. (1999). Neuropharmacology of brain-stimulation–evoked aggression. Neurosci. Biobehav. Rev. 23: 359-389.Google Scholar
  39. Sluyter, F., Bult, A., Lynch, C. B., van Oortmerssen, G. A., and Koolhaas, J. M. (1995). A comparison between house mouse lines selected for attack latency or nest-building: Evidence for a genetic basis of alternative behavioral strategies. Behav. Genet. 25: 247-252.Google Scholar
  40. Sluyter, F., Korte, S. M., Bohus, B., and van Oortmerssen, G. A. (1996). Behavioral stress response of genetically selected aggressive and nonaggressive wild house mice in the shockprobe/ defensive burying test. Pharmacol. Biochem. Behav. 54: 113-116.Google Scholar
  41. Spellman, P. T., Miller, M., Stewart, J., Troup, C., Sarkans, U., Chervitz, S., Bernhart, D., Sherlock, G., Ball, C., Lepage, M., Swiatek, M., Marks, W. L., Goncalves, J., Markel, S., lordan, D., Shojatalab, M., Pizarro, A., White, J., Hubley, R., Deutsch, E., Senger, M., Aronow, B. J., Robinson, A., Bassett, D., Stoeckert, C. J., Jr., and Brazma, A. (2002). Design and implementation of microarray gene expression markup language (MAGE-ML). Genome Biol. 3: RESEARCH0046. Author please supply missing informationGoogle Scholar
  42. Stollberg, J., Urschitz, J., Urban, Z., and Boyd, C. D. (2000). A quantitative evaluation of SAGE. Genome Res. 10: 1241-1248.Google Scholar
  43. Sun, Y., Zhang, L., Johnston, N. L., Torrey, E. F., and Yolken, R. H. (2001). Serial analysis of gene expression in the frontal cortex of patients with bipolar disorder. Br. J. Psychiatry Suppl. 41:137-41.: s137-s141.Google Scholar
  44. van den Berg, A., van der Leij, J., and Poppema, S. (1999). Serial analysis of gene expression: Rapid RT-PCR analysis of unknown SAGE tags. Nucleic Acids Res. 27: e17.Google Scholar
  45. van Der Vegt, B. J., De Boer, S. F., Buwalda, B., de Ruiter, A. J., de Jong, J. G., and Koolhaas, J. M. (2001). Enhanced sensitivity of postsynaptic serotonin-1A receptors in rats and mice with high trait aggression. Physiol. Behav. 74: 205-211.Google Scholar
  46. van Oortmerssen, G. A., and Bakker, T. C. (1981). Artificial selection for short and long attack latencies in wild Mus musculus domesticus. Behav Genet. 11: 115-126.Google Scholar
  47. van Riel, E., Meijer, O. C., Veenema, A. H., and Joels, M. (2002). Hippocampal serotonin responses in short and long attack latency mice. J. Neuroendocrinol. 14: 234-239.Google Scholar
  48. Veenema, A. H., Meijer, O. C., De Kloet, E. R., and Koolhaas, J. M. (2003a). Genetic selection for coping style predicts stressor susceptibility. J. Neuroendocrinol. 15: 256-267.Google Scholar
  49. Veenema, A. H., Meijer, O. C., De Kloet, E. R., Koolhaas, J. M., and Bohus, B. (2003b). Differences in basal and stress-induced HPA regulation of wild house mice selected for high and low aggression. Horm. Behav. 54: 197-204.Google Scholar
  50. Velculescu, V. E., Vogelstein, B., and Kinzler, K. W. (2000). Analysing uncharted transcriptomes with SAGE. Trends Genet. 16: 423-425.Google Scholar
  51. Velculescu, V. E., Zhang, L., Vogelstein, B., and Kinzler, K. W. (1995). Serial analysis of gene expression [see comments]. Science. 270: 484-487.Google Scholar
  52. Virlon, B., Cheval, L., Buhler, J. M., Billon, E., Doucet, A., and Elalouf, J. M. (1999). Serial microanalysis of renal transcriptomes. Proc. Natl. Acad. Sci. USA. 96: 15286-15291.Google Scholar
  53. Yamamoto, M., Wakatsuki, T., Hada, A., and Ryo, A. (2001). Use of serial analysis of gene expression (SAGE) technology. J. Immunol. Methods. 250: 45-66.Google Scholar
  54. Ye, S. Q., Zhang, L. Q., Zheng, F., Virgil, D., and Kwiterovich, P. O. (2000). MiniSAGE: Gene expression profiling using serial analysis of gene expression from 1 microg total RNA. Anal. Biochem. 287: 144-152.Google Scholar
  55. 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: 187-196.Google Scholar

Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Dorine E. M. Feldker
  • E. Ronald de Kloet
  • Menno R. Kruk
  • Nicole A. Datson

There are no affiliations available

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