Skip to main content
Log in

Combining Brain Imaging with Microarray: Isolating Molecules Underlying the Physiologic Disorders of the Brain

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Many diseases of the nervous system cause dysfunction by impairing neuronal physiology more than by altering brain anatomy—including age-related cognitive decline, most psychiatric disorders, and even the earliest stages of Alzheimer's disease. The absence of clear anatomical markers makes it difficult to identify targeted cells, which in turn impedes attempts to isolate the pathogenic molecules that cause physiologic disruption. Here we show how brain imaging and microarray can be used as complimentary techniques that together can characterize the cellular and molecular aspects of this class of diseases.

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.

Similar content being viewed by others

References

  1. Gowers, W. R. 1886. A manual of diseases of the nervous system. Churchill, London.

    Google Scholar 

  2. Ribeiro, S., Mello, C. V., Velho, T., Gardner, T. J., Jarvis, E. D., Pavlides, C. 2002. Induction of hippocampal long-term potentiation during waking leads to increased extrahippocampal zif-268 expression during ensuing rapid-eye-movement sleep. J. Neurosci. 22:10914–23.

    PubMed  Google Scholar 

  3. Koivisto, K., Reinikainen, K. J., Hanninen, T., Vanhanen, M., Helkala, E. L., et al. 1995. Prevalence of age-associated memory impairment in a randomly selected population from eastern Finland. Neurology 45:741–7.

    PubMed  Google Scholar 

  4. Small, S. A. 2001. Age-related memory decline; current concepts and future directions. Arch. Neurol. 58:360–4.

    PubMed  Google Scholar 

  5. Loring, D. W. and Papanicolaou, A. C. 1987. Memory assessment in neuropsychology: theoretical considerations and practical utility. J. Clin. Exp. Neuropsychol. 9:340–58.

    PubMed  Google Scholar 

  6. Zelinski, E. M., Gilewski, M. J., Schaie, K. W. 1993. Individual differences in cross-sectional and 3-year longitudinal memory performance across the adult life span. Psychol. Aging 8:176–86.

    PubMed  Google Scholar 

  7. Zelinski, E. M., Burnight, K. P. 1997. Sixteen-year longitudinal and time lag changes in memory and cognition in older adults. Psychol. Aging 12:503–13.

    PubMed  Google Scholar 

  8. Small, S. A., Stern, Y., Tang, M., Mayeux, R. 1999. Selective decline in memory function among healthy elderly. Neurology 52:1392–6.

    PubMed  Google Scholar 

  9. Jacobs, D. M., Sano, M., Dooneief, G., Marder, K., Bell, K. L., Stern, Y. 1995. Neuropsychological detection and characterization of preclinical Alzheimer's disease [comment] [see comments]. Neurology 45:957–62.

    PubMed  Google Scholar 

  10. Braak, H., Braak, E. 1996. Evolution of the neuropathology of Alzheimer's disease. Acta. Neurol. Scand. Suppl. 165:3–12.

    PubMed  Google Scholar 

  11. Esposito, G., Kirkby, B. S., Van Horn, J. D., Ellmore, T. M., Berman, K. F. 1999. Context-dependent, neural system-specific neurophysiological concomitants of ageing: mapping PET correlates during cognitive activation. Brain 122:963–79.

    PubMed  Google Scholar 

  12. Gomez-Isla, T., Price, J. L., McKeel, D. W., Jr., Morris, J. C., Growdon, J. H., Hyman, B. T. 1996. Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J. Neurosci. 16:4491–500.

    PubMed  Google Scholar 

  13. Gallagher, M., Landfield, P. W., McEwen, B., Meaney, M. J., Rapp, P. R., et al. 1996. Hippocampal neurodegeneration in aging. Science 274:484–5.

    PubMed  Google Scholar 

  14. Gallagher, M. 1997. Animal models of memory impairment. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 352:1711–7.

    PubMed  Google Scholar 

  15. Amaral, D. G., Insausti, R. 1990. The hippocampal formation. In the human nervous system., R. Paxinos, ed. San Diego: Academic Press

    Google Scholar 

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

    PubMed  Google Scholar 

  17. West, M. J., Coleman, P. D., Flood, D. G., Troncoso, J. C. 1994. Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet. 344:769–72.

    PubMed  Google Scholar 

  18. Takahashi, R. H., Milner, T. A., Li, F., Nam, E. E., Edgar, M. A., et al. 2002. Intraneuronal Alzheimer abeta42 accumulates in multivesicular bodies and is associated with synaptic pathology. Am. J. Pathol. 161:1869–79.

    PubMed  Google Scholar 

  19. D'Andrea, M. R., Nagele, R. G., Wang, H. Y., Lee, D. H. 2002. Consistent immunohistochemical detection of intracellular beta-amyloid42 in pyramidal neurons of Alzheimer's disease entorhinal cortex. Neurosci. Lett. 333:163–6.

    PubMed  Google Scholar 

  20. Cataldo, A., Rebeck, G. W., Ghetri, B., Hulette, C., Lippa, C., et al. 2001. Endocytic disturbances distinguish among subtypes of Alzheimer's disease and related disorders. Ann. Neurol. 50:661–5.

    PubMed  Google Scholar 

  21. Selkoe, D. J. 2002. Alzheimer's disease is a synaptic failure. Science 298:789–91.

    PubMed  Google Scholar 

  22. Sokoloff, L. 1996. Cerebral metabolism and visualization of cerebral activity. Pages 579–602, In Comprehensive human physiology, R. Gregor, U. Windhorst, eds. Springer-Verlag, New York.

    Google Scholar 

  23. Barnes, C. A. 1994. Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 17:13–8.

    PubMed  Google Scholar 

  24. Kety, S. 1960. Theory of blood-tissue exchange and its application to measurment of blood flow. Method Med. Res. 8:223.

    Google Scholar 

  25. Siesjo, B. 1978. Brain energy metabolism. Wiley, New York.

    Google Scholar 

  26. Hyder, F., Renken, R., Kennan, R. P., Rothman, D. L. 2000. Quantitative multi-modal functional MRI with blood oxygenation level dependent exponential decays adjusted for flow attenuated inversion recovery (BOLDED AFFAIR). Magn. Reson. Imaging 18:227–35.

    PubMed  Google Scholar 

  27. Hyder, F., Kida, I., Behar, K. L., Kennan, R. P., Maciejewski, P. K., Rothman, D. L. 2001. Quantitative functional imaging of the brain: towards mapping neuronal activity by BOLD fMRI. NMR Biomed. 14:413–31.

    PubMed  Google Scholar 

  28. Davis, T. L., Kwong, K. K., Weisskoff, R. M., Rosen, B. R. 1998. Calibrated functional MRI: mapping the dynamics of oxidative metabolism. Proc. Natl. Acad. Sci. USA 95:1834–9.

    PubMed  Google Scholar 

  29. Cohen, E. R., Ugurbil, K., Kim, S. G. 2002. Effect of basal conditions on the magnitude and dynamics of the blood oxygenation level-dependent fMRI response. J. Cereb. Blood. Flow. Metab. 22:1042–53.

    PubMed  Google Scholar 

  30. Small, S. A., Nava, A. S., Perera, G. M., Delapaz, R., Stern, Y. 2000. Evaluating the function of hippocampal subregions with high-resolution MRI in Alzheimer's disease and aging [In Process Citation]. Microsc. Res. Tech. 51:101–8.

    PubMed  Google Scholar 

  31. Mueggler, T., Sturchler-Pierrat, C., Baumann, D., Rausch, M., Staufenbiel, M., Rudin, M. 2002. Compromised hemodynamic response in amyloid precursor protein transgenic mice. J. Neurosci. 22:7218–24.

    PubMed  Google Scholar 

  32. Bach, M. E., Barad, M., Son, H., Zhuo, M., Lu, Y. F., et al. 1999. Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc. Natl. Acad. Sci. USA 96:5280–5.

    PubMed  Google Scholar 

  33. Hsia, A. Y., Masliah, E., McConlogue, L., Yu, G. Q., Tatsuno, G., et al. 1999. Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models. Proc. Natl. Acad. Sci. USA 96:3228–33.

    PubMed  Google Scholar 

  34. Smith, C. B., Goochee, C., Rapoport, S. I., Sokoloff, L. 1980. Effects of ageing on local rates of cerebral glucose utilization in the rat. Brain 103:351–65.

    PubMed  Google Scholar 

  35. Gonzalez-Lima, F. 1987. Cytochrome oxidase in neuronal metabolism and Alzheimer's disease. Plenum Press, New York.

    Google Scholar 

  36. Small, S. A. 2003. Microscopic Measurements of Brain Metabolism with MRI; An effective approach for diagnosing Alzheimer's disease and mapping its course. Alzheimer's Disease and Associative Disorders 17:154–161.

    Google Scholar 

  37. Small, S., Wu, E., Bartsch, D., Lacefield, C., DeLaPaz, R., et al. 2000. Imaging physiologic dysfunction of individual hippocampal subregions in humans and genetically modified mice. Neuron. 28:653–64.

    PubMed  Google Scholar 

  38. Small, S. A., Tsai, W. Y., DeLaPaz, R., Mayeux, R., Stern, Y. 2002. Imaging hippocampal function across the human life span: is memory decline normal or not? Ann. Neurol. 51:290–5.

    PubMed  Google Scholar 

  39. Colangelo, V., Schurr, J., Ball, M. J., Pelaez, R. P., Bazan, N. G., Lukiw, W. J. 2002. Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and proinflammatory signaling. J. Neurosci. Res. 70:462–73.

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  41. Loring, J. F., Wen, X., Lee, J. M., Seilhamer, J., Somogyi, R. 2001. A gene expression profile of Alzheimer's disease. DNA Cell. Biol. 20:683–95.

    PubMed  Google Scholar 

  42. Bahn, S., Augood, S. J., Ryan, M., Standaert, D. G., Starkey, M., Emson, P. C. 2001. Gene expression profiling in the post-mortem human brain—no cause for dismay. J. Chem. Neuroanat. 22:79–94.

    PubMed  Google Scholar 

  43. Van Deerlin, V., Ginsberg, S. D., Lee, V. M., Trojanowski, J. Q. 2002. The use of fixed human post mortem brain tissue to study mRNA expression in neurodegenerative diseases: applications of microdissection and mRNA amplification. Pages 201–235, in Microarrays for the neurosciences: an essential guide, D. Geschwind, J. Gregg, eds. MIT Press, Boston.

    Google Scholar 

  44. Amaral, D. G. 1993. Emerging principles of intrinsic hippocampal organization. Curr. Opin. Neurobiol. 3:225–9.

    PubMed  Google Scholar 

  45. Marinkovic, S., Milisavljevic, M., Puskas, L. 1992. Microvascular anatomy of the hippocampal formation. Surg. Neurol. 37:339–49.

    PubMed  Google Scholar 

  46. Spillane, J. D. 1981. The doctrine of the nerves. Oxford University Press, Oxford.

    Google Scholar 

  47. Chawla, M. K., Barnes, C. A., Rapp, P. R., Pierce, A. L., Small, S. A. 2003. Aging selectively targets the dentate gyrus in Rats, Monkeys, and Humans. 34th annual meeting of the Society for Neuroscience. New Orleans, 2003.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Scott A. Small.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pierce, A., Small, S.A. Combining Brain Imaging with Microarray: Isolating Molecules Underlying the Physiologic Disorders of the Brain. Neurochem Res 29, 1145–1152 (2004). https://doi.org/10.1023/B:NERE.0000023601.50101.7f

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000023601.50101.7f

Navigation