Skip to main content
Log in

Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Technical and experimental advances in microaspiration techniques, RNA amplification, quantitative real-time polymerase chain reaction (qPCR), and cDNA microarray analysis have led to an increase in the number of studies of single-cell gene expression. In particular, the central nervous system (CNS) is an ideal structure to apply single-cell gene expression paradigms. Unlike an organ that is composed of one principal cell type, the brain contains a constellation of neuronal and noneuronal populations of cells. A goal is to sample gene expression from similar cell types within a defined region without potential contamination by expression profiles of adjacent neuronal subpopulations and noneuronal cells. The unprecedented resolution afforded by single-cell RNA analysis in combination with cDNA microarrays and qPCR-based analyses allows for relative gene expression level comparisons across cell types under different experimental conditions and disease states. The ability to analyze single cells is an important distinction from global and regional assessments of mRNA expression and can be applied to optimally prepared tissues from animal models as well as postmortem human brain tissues. This focused review illustrates the potential power of single-cell gene expression studies within the CNS in relation to neurodegenerative and neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia, respectively.

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. Ginsberg, S. D., Hemby, S. E., Lee, V. M-Y., 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 

  2. Ginsberg, S. D., Crino, P. B., Hemby, S. E., Weingarten, J. A., Lee, V. M-Y., Eberwine, J. H., and Trojanowski, J. Q. 1999. Predominance of neuronal mRNAs in individual Alzheimer's disease senile plaques. Ann. Neurol. 45:174–181.

    PubMed  Google Scholar 

  3. Ginsberg, S. D. and Che, S. 2002. RNA amplification in brain tissues. Neurochem. Res. 27:981–992.

    PubMed  Google Scholar 

  4. Mufson, E. J., Counts, S. E., and Ginsberg, S. D. 2002. Single cell gene expression profiles of nucleus basalis cholinergic neurons in Alzheimer's disease. Neurochem. Res. 27:1035–1048.

    PubMed  Google Scholar 

  5. Hemby, S. E., Ginsberg, S. D., Brunk, B., Arnold, S. E., Trojanowski, J. Q., and Eberwine, J. H. 2002. Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Arch. Gen. Psychiat. 59:631–640.

    PubMed  Google Scholar 

  6. Hemby, S. E., Trojanowski, J. Q., and Ginsberg, S. D. 2003. Neuron-specific age-related decreases in dopamine receptor subtype mRNAs. J. Comp. Neurol. 456:176–183.

    PubMed  Google Scholar 

  7. Van Deerlin, V. M. D., Ginsberg, S. D., Lee, V. M-Y., and 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, Geschwind, D. H. and Gregg, J. P, (eds.), MIT Press: Boston.

    Google Scholar 

  8. Van Deerlin, V. M. D., Ginsberg, S. D., Lee, V. M-Y., and Trojanowski, J. Q. (2000). Fixed post mortem brain tissue for mRNA expression analysis in neurodegenerative diseases. Pages 118–128, in Geschwind, D. H. (ed.). DNA microarrays: the new frontier in gene discovery and gene expression analysis, Society for Neuroscience: Washington, DC.

    Google Scholar 

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

    PubMed  Google Scholar 

  10. Leonard, S., Logel, J., Luthman, D., Casanova, M., Kirch, D., and Freedman, R. 1993. Biological stability of mRNA isolated from human postmortem brain collections. Biol. Psychiatry 33:456–466.

    PubMed  Google Scholar 

  11. von Bertalanffy, L. and Bickis, I. 1956. Identification of cytoplasmic basophilia (ribonucleic acid) by fluorescence microscopy. J. Histochem. Cytochem. 4:481–493.

    PubMed  Google Scholar 

  12. Mikel, U. V. and Becker Jr., R. L. 1991. A comparative study of quantitative stains for DNA in image cytometry. Analyt. Quant. Cytol. Histol. 13:253–260.

    Google Scholar 

  13. Mai, J. K., Schmidt-Kastner, R., and Tefett, H-B. 1984. Use of acridine orange for histologic analysis of the central nervous system. J. Histochem. Cytochem. 32:97–104.

    PubMed  Google Scholar 

  14. Sarnat, H. B., Curry, B., Rewcastle, N. B., and Trevenen, C. L. 1986. Cytoplasmic RNA in nervous system tumors in children: a fluorochromic histochemical study using acridine orange. Can. J. Neurol. Sci. 13:31–41.

    PubMed  Google Scholar 

  15. Ginsberg, S. D., Crino, P. B., Lee, V. M-Y., Eberwine, J. H., and Trojanowski, J. Q. 1997. Sequestration of RNA in Alzheimer's disease neurofibrillary tangles and senile plaques. Ann. Neurol. 41:200–209.

    PubMed  Google Scholar 

  16. Ginsberg, S. D., Galvin, J. E., Chiu, T-S., Lee, V. M-Y., Masliah, E., and Trojanowski, J. Q. 1998. RNA sequestration to pathological lesions of neurodegenerative disorders. Acta Neuropathol. 96:487–494.

    PubMed  Google Scholar 

  17. Sarnat, H. B., Curry, B., Rewcastle, N. B., and Trevenen, C. L. 1987. Gliosis and glioma distinguished by acridine orange. Can. J. Neurol. Sci. 14:31–35.

    PubMed  Google Scholar 

  18. Dickey, C. A., Loring, J. F., Montgomery, J., Gordon, M. N., Eastman, P. S., and Morgan, D. 2003. Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J. Neurosci. 23:5219–5226.

    PubMed  Google Scholar 

  19. Mandel, S., Weinreb, O., and Youdim, M. 2003. Using cDNA microarray to assess Parkinson's disease models and the effects of neuroprotective drugs. Trends Pharmacol. Sci. 24:184–191.

    PubMed  Google Scholar 

  20. Grunblatt, E., Mandel, S., Maor, G., and Youdim, M. B. 2001. Gene expression analysis in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice model of Parkinson's disease using cDNA microarray: effect of R-apomorphine. J. Neurochem. 78:1–12.

    Google Scholar 

  21. 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.

    PubMed  Google Scholar 

  22. Reyes, T. M., Walker, J. R., DeCino, C., Hogenesch, J. B., and Sawchenko, P. E. 2003. Categorically distinct acute stressors elicit dissimilar transcriptional profiles in the paraventricular nucleus of the hypothalamus. J. Neurosci. 23:5607–5616.

    PubMed  Google Scholar 

  23. Loring, J. F., Wen, X., Lee, J. M., Seilhamer, J., and Somogyi, R. 2001. A gene expression profile of Alzheimer's disease. DNA Cell Biol. 20:683–695.

    PubMed  Google Scholar 

  24. Colangelo, V., Schurr, J., Ball, M. J., Pelaez, R. P., Bazan, N. G., and 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 pro-inflammatory signaling. J. Neurosci. Res. 70:462–473.

    PubMed  Google Scholar 

  25. Malaspina, A., Kaushik, N., and de Belleroche, J. 2001. Differential expression of 14 genes in amyotrophic lateral sclerosis spinal cord detected using gridded cDNA arrays. J. Neurochem. 77:132–145.

    PubMed  Google Scholar 

  26. Carmel, J. B., Galante, A., Soteropoulos, P., Tolias, P., Recce, M., Young, W., and Hart, R. P. 2001. Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss. Physiol. Genomics 7:201–213.

    PubMed  Google Scholar 

  27. Yoshihara, T., Ishigaki, S., Yamamoto, M., Liang, Y., Niwa, J., Takeuchi, H., Doyu, M., and Sobue, G. 2002. Differential expression of inflammation-and apoptosis-related genes in spinal cords of a mutant SOD1 transgenic mouse model of familial amyotrophic lateral sclerosis. J. Neurochem. 80:158–167.

    PubMed  Google Scholar 

  28. 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., and Steinman, L. 2002. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 8:500–508.

    PubMed  Google Scholar 

  29. Mycko, M. P., Papoian, R., Boschert, U., Raine, C. S., and Selmaj, K. W. 2003. cDNA microarray analysis in multiple sclerosis lesions: detection of genes associated with disease activity. Brain 126:1048–1057.

    PubMed  Google Scholar 

  30. Mimmack, M. L., Ryan, M., Baba, H., Navarro-Ruiz, J., Iritani, S., Faull, R. L., McKenna, P. J., Jones, P. B., Arai, H., Starkey, M., Emson, P. C., and Bahn, S. 2002. Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. Proc. Natl. Acad. Sci. USA 99: 4680–4685.

    PubMed  Google Scholar 

  31. Middleton, F. A., Mirnics, K., Pierri, J. N., Lewis, D. A., and Levitt, P. 2002. Gene expression profiling reveals alterations of specific metabolic pathways in schizophrenia. J. Neurosci. 22: 2718–2729.

    PubMed  Google Scholar 

  32. Hakak, Y., Walker, J. R., Li, C., Wong, W. H., Davis, K. L., Buxbaum, J. D., Haroutunian, V., and Fienberg, A. A. 2001. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc. Natl. Acad. Sci. USA 98:4746–4751.

    PubMed  Google Scholar 

  33. 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 

  34. Ginsberg, S. D. 2001. Gene expression profiling using single cell microdissection combined with cDNA microarrays. Pages 61–70, in Geschwind, D. H. (ed.). DNA microarrays: the new frontier in gene discovery and gene expression analysis., Society for Neuroscience Press, Washington DC.

    Google Scholar 

  35. Bonner, R. F., Emmert-Buck, M., Cole, K., Pohida, T., Chuaqui, R., Goldstein, S., and Liotta, L. A. 1997. Laser capture microdissection: molecular analysis of tissue. Science 278:1481–1483.

    PubMed  Google Scholar 

  36. Emmert-Buck, M. R., Bonner, R. F., Smith, P. D., Chuaqui, R. F., Zhuang, Z., Goldstein, S. R., Weiss, R. A., and Liotta, L. A. 1996. Laser capture microdissection. Science 274:998–1001.

    PubMed  Google Scholar 

  37. Fend, F., Emmert-Buck, M. R., Chuaqui, R., Cole, K., Lee, J., Lotto, L. A., and Raffeld, M. 1999. Immuno-LCM: laser capture microdis-section of immunostained frozen sections for mRNA analysis. Am. J. Pathol. 154:61–66.

    PubMed  Google Scholar 

  38. Goldsworthy, S. M., Stockton, P. S., Trempus, C. S., Foley, J. F., and Maronpot, R. R. 1999. Effects of fixation on RNA extraction and amplification from laser capture microdissected tissue. Mol. Carcinog. 25:86–91.

    PubMed  Google Scholar 

  39. Simone, N. L., Remaley, A. T., Charboneau, L., Petricoin, E. F., 3rd, Glickman, J. W., Emmert-Buck, M. R., Fleisher, T. A., and Liotta, L. A. 2000. Sensitive immunoassay of tissue cell proteins procured by laser capture microdissection. Am. J. Pathol. 156: 445–452.

    PubMed  Google Scholar 

  40. Suarez-Quian, C. A., Goldstein, S. R., Pohida, T., Smith, P. D., Peterson, J. I., Wellner, E., Ghany, M., and Bonner, R. F. 1999. Laser capture microdissection of single cells from complex tissues. BioTechniques 26:328–335.

    PubMed  Google Scholar 

  41. Crino, P. B., Khodakhah, K., Becker, K., Ginsberg, S. D., Hemby, S., and Eberwine, J. H. 1998. Presence and phosphorylation of transcription factors in dendrites. Proc. Natl. Acad. Sci. USA 95:2313–2318.

    PubMed  Google Scholar 

  42. Che, S. and Ginsberg, S. D. 2004. Amplification of transcripts using terminal continuation. Lab. Invest. 84:233–242.

    Google Scholar 

  43. Kacharmina, J. E., Crino, P. B., and Eberwine, J. 1999. Preparation of cDNA from single cells and subcellular regions. Methods Enzymol. 303:3–18.

    PubMed  Google Scholar 

  44. Sambrook, J., Fritsch, E., and Maniatis, T. 1989. Molecular cloning: a laboratory manual. Second edition. Cold Spring Harbor Laboratory Press, Cold Spring Harbor.

    Google Scholar 

  45. Kadkol, S. S., Gage, W. R., and Pasternack, G. R. 1999. In situ hybridization—theory and practice. Mol. Diagn. 4:169–183.

    PubMed  Google Scholar 

  46. Hashimoto, T., Volk, D. W., Eggan, S. M., Mirnics, K., Pierri, J. N., Sun, Z., Sampson, A. R., and Lewis, D. A. 2003. Gene expression deficits in a subclass of GABA neurons in the prefrontal cortex of subjects with schizophrenia. J. Neurosci. 23:6315–6326.

    PubMed  Google Scholar 

  47. Brail, L. H., Jang, A., Billia, F., Iscove, N. N., Klamut, H. J., and Hill, R. P. 1999. Gene expression in individual cells: analysis using global single cell reverse transcription polymerase chain reaction (GSC RT-PCR). Mutat. Res. 406:45–54.

    PubMed  Google Scholar 

  48. Holland, P. M., Abramson, R. D., Watson, R., and Gelfand, D. H. 1991. Detection of specific polymerase chain reaction product by utilizing the 5′—3′ exonuclease activity of Thermus aquaticus DNA polymerase. Proc. Natl. Acad. Sci. USA 88:7276–7280.

    PubMed  Google Scholar 

  49. Cardullo, R. A., Agrawal, S., Flores, C., Zamecnik, P. C., and Wolf, D. E. 1988. Detection of nucleic acid hybridization by nonradiative fluorescence resonance energy transfer. Proc. Natl. Acad. Sci. USA 85:8790–8794.

    PubMed  Google Scholar 

  50. Bustin, S. A. 2002. Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J. Mol. Endocrinol. 29:23–39.

    PubMed  Google Scholar 

  51. 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.

    PubMed  Google Scholar 

  52. Eberwine, J., Kacharmina, J. E., Andrews, C., Miyashiro, K., McIntosh, T., Becker, K., Barrett, T., Hinkle, D., Dent, G., and Marciano, P. 2001. mRNA expression analysis of tissue sections and single cells. J. Neurosci. 21:8310–8314.

    PubMed  Google Scholar 

  53. Brown, P. O. and Botstein, D. 1999. Exploring the new world of the genome with DNA microarrays. Nat. Genet. 21(Suppl):33–37.

    PubMed  Google Scholar 

  54. Eisen, M. B. and Brown, P. O. 1999. DNA arrays for analysis of gene expression. Methods Enzymol. 303:179–205.

    PubMed  Google Scholar 

  55. Lockhart, D. J., Dong, H., Byrne, M. C., Follettie, M. T., Gallo, M. V., Chee, M. S., Mittmann, M., Wang, C., Kobayashi, M., Horton, H., and Brown, E. L. 1996. Expression monitoring by hybridization to high-density oligonucleotide arrays. Nat. Biotechnol. 14:1675–1680.

    PubMed  Google Scholar 

  56. Gygi, S. P., Rochon, Y., Franza, B. R., and Aebersold, R. 1999. Correlation between protein and mRNA abundance in yeast. Mol. Cell. Biol. 19:1720–1730.

    PubMed  Google Scholar 

  57. Ginsberg, S. D., Schmidt, M. L., Crino, P. B., Eberwine, J. H., Lee, V. M-Y., and Trojanowski, J. Q., 1999. Molecular pathology of Alzheimer's disease and related disorders. Pages 603–653, in Cerebral cortex, vol. 14: neurodegenerative and age-related changes in structure and function of cerebral cortex, Peters, A. and Morrison, J. H. (eds.), Kluwer Academic/Plenum, New York.

    Google Scholar 

  58. Harrison, P. J., Barton, A. J., Najlerahim, A., McDonald, B., and Pearson, R. C. 1991. Regional and neuronal reductions of polyadenylated messenger RNA in Alzheimer's disease. Psychol. Med. 21:855–866.

    PubMed  Google Scholar 

  59. Griffin, W. S., Ling, C., White, C. L., and Morrison-Bogorad, M. 1990. Polyadenylated messenger RNA in paired helical filament-immunoreactive neurons in Alzheimer disease. Alz. Dis. Assoc. Dis. 4:69–78.

    Google Scholar 

  60. Joyce, J. N., Kaeger, C., Ryoo, H., and Goldsmith, S. 1993. Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease. Neurosci. Lett. 154:171–174.

    PubMed  Google Scholar 

  61. Ryoo, H. L. and Joyce, J. N. 1994. Loss of dopamine D2 receptors varies along the rostrocaudal axis of the hippocampal complex in Alzheimer's disease. J. Comp. Neurol. 348:94–110.

    PubMed  Google Scholar 

  62. Cataldo, A. M., Barnett, J. L., Berman, S. A., Li, J., Quarless, S., Bursztajn, S., Lippa, C., and Nixon, R. A. 1995. Gene expression and cellular content of cathepsin D in Alzheimer's disease brain: evidence for early up-regulation of the endosomal-lysosomal system. Neuron 14:671–680.

    PubMed  Google Scholar 

  63. Cataldo, A. M., Hamilton, D. J., Barnett, J. L., Paskevich, P. A., and Nixon, R. A. 1996. Properties of the endosomal-lysosomal system in the human central nervous system: disturbances mark most neurons in populations at risk to degenerate in Alzheimer's disease. J. Neurosci. 16:186–199.

    PubMed  Google Scholar 

  64. Nixon, R. A., Cataldo, A. M., and Mathews, P. M. 2000. The endosomal-lysosomal system of neurons in Alzheimer's disease pathogenesis: a review. Neurochem. Res. 25:1161–1172.

    PubMed  Google Scholar 

  65. Goedert, M., Trojanowski, J. Q., and Lee, V. M-Y. 1997. The neurofibrillary pathology of Alzheimer's disease. Pages 613–627, in The Molecular and Genetic Basis of Neurological Disease, Second ed., Rosenberg, R. N., et al., (eds.), Butterworth-Heinemann, Boston.

    Google Scholar 

  66. Selkoe, D. J. 1997. Alzheimer's disease: genotypes, phenotypes, and treatments. Science 275:630–631.

    PubMed  Google Scholar 

  67. Itagaki, S., McGeer, P. L., Akiyama, H., Zhu, S., and Selkoe, D. 1989. Relationship of microglia and astrocytes to amyloid deposits of Alzheimer disease. J. Neuroimmunol. 24:173–182.

    PubMed  Google Scholar 

  68. Eikelenboom, P. and Veerhuis, R. 1996. The role of complement and activated microglia in the pathogenesis of Alzheimer's disease. Neurobiol. Aging 17:673–680.

    PubMed  Google Scholar 

  69. Mesulam, M. M., Mufson, E. J., Levey, A. I., and Wainer, B. H. 1983. Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J. Comp. Neurol. 214:170–197.

    PubMed  Google Scholar 

  70. Bartus, R. T., Dean, R. L., 3rd, Beer, B., and Lippa, A. S. 1982. The cholinergic hypothesis of geriatric memory dysfunction. Science. 217:408–414.

    PubMed  Google Scholar 

  71. Baxter, M. G. and Chiba, A. A. 1999. Cognitive functions of the basal forebrain. Curr. Opin. Neurobiol. 9:178–183.

    PubMed  Google Scholar 

  72. Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., and Delong, M. R. 1982. Alzheimer's disease and senile dementia: loss of neurons in the basal forebrain. Science 215:1237–1239.

    PubMed  Google Scholar 

  73. Davies, P. and Maloney, A. J. 1976. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2:1403.

    Google Scholar 

  74. Mufson, E. J., Bothwell, M., and Kordower, J. H. 1989. Loss of nerve growth factor receptor-containing neurons in Alzheimer's disease: a quantitative analysis across subregions of the basal forebrain. Exp. Neurol. 105:221–232.

    PubMed  Google Scholar 

  75. Bierer, L. M., Haroutunian, V., Gabriel, S., Knott, P. J., Carlin, L. S., Purohit, D. P., Perl, D. P., Schmeidler, J., Kanof, P., and Davis, K. L. 1995. Neurochemical correlates of dementia severity in Alzheimer's disease: relative importance of the cholinergic deficits. J. Neurochem. 64:749–760.

    PubMed  Google Scholar 

  76. Counts, S. E., Perez, S. E., Ginsberg, S. D., de Lacalle, S., and Mufson, E. J. 2003. Galanin plasticity and Alzheimer's disease. Molecular Interventions 3:23–40.

    Google Scholar 

  77. Cullen, K. M. and Halliday, G. M. 1998. Neurofibrillary degeneration and cell loss in the nucleus basalis in comparison to cortical Alzheimer pathology. Neurobiol. Aging 19:297–306.

    PubMed  Google Scholar 

  78. Sassin, I., Schultz, C., Thal, D. R., Rub, U., Arai, K., Braak, E., and Braak, H. 2000. Evolution of Alzheimer's disease-related cytoskeletal changes in the basal nucleus of Meynert. Acta Neuropathol. (Berl). 100:259–69.

    Google Scholar 

  79. Struble, R. G., Cork, L. C., Whitehouse, P. J., and Price, D. L. 1982. Cholinergic innervation in neuritic plaques. Science 216: 413–415.

    PubMed  Google Scholar 

  80. German, D. C., Yazdani, U., Speciale, S. G., Pasbakhsh, P., Games, D., and Liang, C. L. 2003. Cholinergic neuropathology in a mouse model of Alzheimer's disease. J. Comp. Neurol. 462:371–381.

    PubMed  Google Scholar 

  81. Buxbaum, J. D., Thinakaran, G., Koliatsos, V., O'Callahan, J., Slunt, H. H., Price, D. L., and Sisodia, S. S. 1998. Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path. J. Neurosci. 18:9629–9637.

    PubMed  Google Scholar 

  82. Sheng, J. G., Price, D. L., and Koliatsos, V. E. 2002. Disruption of corticocortical connections ameliorates amyloid burden in terminal fields in a transgenic model of Abeta amyloidosis. J. Neurosci. 22:9794–9799.

    PubMed  Google Scholar 

  83. Lazarov, O., Lee, M., Peterson, D. A., and Sisodia, S. S. 2002. Evidence that synaptically released beta-amyloid accumulates as extracellular deposits in the hippocampus of transgenic mice. J. Neurosci. 22:9785–9793.

    PubMed  Google Scholar 

  84. Lencz, T., Cornblatt, B., and Bilder, R. M. 2001. Neurodevelopmental models of schizophrenia: pathophysiologic synthesis and directions for intervention research. Psychopharmacol. Bull. 35:95–125.

    PubMed  Google Scholar 

  85. Johns, L. C. and van Os, J. 2001. The continuity of psychotic experiences in the general population. Clin Psychol Rev. 21:1125–1141.

    PubMed  Google Scholar 

  86. Lewis, D. A. 2002. In pursuit of the pathogenesis and pathophysiology of schizophrenia: where do we stand? Am. J. Psychiatry 159:1467–1469.

    PubMed  Google Scholar 

  87. Kurtz, M. M., Moberg, P. J., Gur, R. C., and Gur, R. E. 2001. Approaches to cognitive remediation of neuropsychological deficits in schizophrenia: a review and meta-analysis. Neuropsychol. Rev. 11:197–210.

    PubMed  Google Scholar 

  88. Gur, R. C. and Gur, R. E. 2002. Neuroimaging applications in elderly patients. Am. J. Geriatr. Psychiatry 10:5–11.

    PubMed  Google Scholar 

  89. Arnold, S. E., Trojanowski, J. Q., Gur, R. E., Blackwell, P., Han, L. Y., and Choi, C. 1998. Absence of neurodegeneration and neural injury in the cerebral cortex in a sample of elderly patients with schizophrenia. Arch. Gen. Psychiatry 55:225–232.

    PubMed  Google Scholar 

  90. Trojanowski, J. Q. and Arnold, S. E. 1995. In pursuit of the molecular neuropathology of schizophrenia. Arch. Gen. Psychiatry 52: 274–276.

    PubMed  Google Scholar 

  91. Blalock, E. M., Chen, K. C., Sharrow, K., Herman, J. P., Porter, N. M., Foster, T. C., and Landfield, P. W. 2003. Gene microarrays in hippocampal aging: statistical profiling identifies novel processes correlated with cognitive impairment. J. Neurosci. 23: 3807–3819.

    PubMed  Google Scholar 

  92. Prolla, T. A. 2002. DNA microarray analysis of the aging brain. Chem. Senses 27:299–306.

    PubMed  Google Scholar 

  93. Bannon, M. J., Poosch, M. S., Xia, Y., Goebel, D. J., Cassin, B., and Kapatos, G. 1992. Dopamine transporter mRNA content in human substantia nigra decreases precipitously with age. Proc. Natl. Acad. Sci. USA 89:7095–7099.

    PubMed  Google Scholar 

  94. Bannon, M. J. and Whitty, C. J. 1997. Age-related and regional differences in dopamine transporter mRNA expression in human midbrain. Neurology. 48:969–977.

    PubMed  Google Scholar 

  95. Emborg, M. E., Ma, S. Y., Mufson, E. J., Levey, A. I., Taylor, M. D., Brown, W. D., Holden, J. E., and Kordower, J. H. 1998. Age-related declines in nigral neuronal function correlate with motor impairments in rhesus monkeys. J. Comp. Neurol. 401: 253–265.

    PubMed  Google Scholar 

  96. Ma, S. Y., Roytt, M., Collan, Y., and Rinne, J. O. 1999. Unbiased morphometrical measurements show loss of pigmented nigral neurones with ageing. Neuropathol. Appl. Neurobiol. 25:394–399.

    PubMed  Google Scholar 

  97. Zola-Morgan, S. and Squire, L. R. 1993. Neuroanatomy of memory. Annu. Rev. Neurosci. 16:547–563.

    PubMed  Google Scholar 

  98. Zola-Morgan, S., Squire, L. R., and Ramus, S. J. 1994. Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system. Hippocampus 4:483–495.

    PubMed  Google Scholar 

  99. Akil, M., Edgar, C. L., Pierri, J. N., Casali, S., and Lewis, D. A. 2000. Decreased density of tyrosine hydroxylase-immunoreactive axons in the entorhinal cortex of schizophrenic subjects. Biol. Psychiatry 47:361–370.

    PubMed  Google Scholar 

  100. Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Gatley, S. J., MacGregor, R. R., Schlyer, D. J., Hitzemann, R., and Wolf, A. P. 1996. Measuring age-related changes in dopamine D2 receptors with 11C-raclopride and 18F-N-methylspiroperidol. Psychiatry Res. 67:11–16.

    PubMed  Google Scholar 

  101. Volkow, N. D., Ding, Y. S., Fowler, J. S., Wang, G. J., Logan, J., Gatley, S. J., Hitzemann, R., Smith, G., Fields, S. D., and Gur, R. 1996. Dopamine transporters decrease with age. J. Nucl. Med. 37:554–559.

    PubMed  Google Scholar 

  102. Volkow, N. D., Wang, G. J., Fowler, J. S., Ding, Y. S., Gur, R. C., Gatley, J., Logan, J., Moberg, P. J., Hitzemann, R., Smith, G., and Pappas, N. 1998. Parallel loss of presynaptic and postsynaptic dopamine markers in normal aging. Ann. Neurol. 44:143–147.

    PubMed  Google Scholar 

  103. Rinne, J. O., Lonnberg, P., and Marjamaki, P. 1990. Age-dependent decline in human brain dopamine D1 and D2 receptors. Brain Res. 508:349–352.

    PubMed  Google Scholar 

  104. Amenta, F., Mignini, F., Ricci, A., Sabbatini, M., Tomassoni, D., and Tayebati, S. K. 2001. Age-related changes of dopamine receptors in the rat hippocampus: a light microscope autoradiography study. Mech. Ageing Dev. 122:2071–2083.

    PubMed  Google Scholar 

  105. Kemppainen, N., Laine, M., Laakso, M. P., Kaasinen, V., Nagren, K., Vahlberg, T., Kurki, T., and Rinne, J. O. 2003. Hippocampal dopamine D2 receptors correlate with memory functions in Alzheimer's disease. Eur. J. Neurosci. 18:149–154.

    PubMed  Google Scholar 

  106. Kaasinen, V. and Rinne, J. O. 2002. Functional imaging studies of dopamine system and cognition in normal aging and Parkinson's disease. Neurosci. Biobehav. Rev. 26:785–793.

    PubMed  Google Scholar 

  107. Colantuoni, C., Purcell, A. E., Bouton, C. M., and Pevsner, J. 2000. High throughput analysis of gene expression in the human brain. J. Neurosci. Res. 59:1–10.

    PubMed  Google Scholar 

  108. Serafini, T. 1999. Of neurons and gene chips. Curr. Opin. Neurobiol. 9:641–644.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Stephen D. Ginsberg.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ginsberg, S.D., Elarova, I., Ruben, M. et al. Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders. Neurochem Res 29, 1053–1064 (2004). https://doi.org/10.1023/B:NERE.0000023593.77052.f7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000023593.77052.f7

Navigation