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Journal of Autism and Developmental Disorders

, Volume 31, Issue 6, pp 551–555 | Cite as

Functional Genomics Approaches to a Primate Model of Autistic Symptomology

  • Scott E. Hemby
  • Mar M. Sanchez
  • James T. Winslow
Article

Abstract

Several studies indicate a primary dysfunction of the temporal lobe in autism, specifically the hippocampal formation and entorhinal cortex (EC). Assessment of gene expression in the EC and hippocampus will provide insight into the subtle alterations in neuronal function associated with autism. To this end, evaluations in a primate model of social attachment, which produces behaviors associated with autism, in addition to the use of human post-mortem tissue from individuals diagnosed with autism will provide heretofore unattainable information of how the complex neural circuitry of this region is altered in autism. Identification of altered expression of multiple genes should provide a molecular “fingerprint” of autism and may provide new targets for pharmacotherapeutic intervention.

Autism gene expression temporal lobe rhesus monkey functional genomics 

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REFERENCES

  1. Bachevalier, J. (1991). An animal model for childhood autism: Memory loss and socioemotional disturbances following neonatal damage to the limbic system in monkeys. In C. A. Tamminga and S. C. Schulz (Eds.), Schizophrenia Research. Advances in Neuropsychiatry and Psychopharmacology, Vol. 1, pp. 129–140, New York: Raven Press, Publishers.Google Scholar
  2. Bachevalier, J. (1994). Medial temporal lobe structures and autism: a review of clinical and experimental findings. Neuropsychologia, 32, 627–648.CrossRefPubMedGoogle Scholar
  3. Bachevalier, J. (1996). Brief report: Medial temporal lobe and autism: A putative animal model in primates. Journal of Autism and Developmental Disorders, 26, 217–220.PubMedGoogle Scholar
  4. Bauman, M. L. (1996). Brief report: Neuroanatomic observations of the brain in pervasive developmental disorders. Journal of Autism and Developmental Disorders, 26, 199–203.PubMedGoogle Scholar
  5. Bauman, M. L., & Kemper, T. L. (1985). Histoanatomic observations of the brain in early autism. Neurology, 35, 866–874.PubMedGoogle Scholar
  6. Bolton, P. F., & Griffiths, P. D. (1997). Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet, 349(9049), 392–395.PubMedGoogle Scholar
  7. Breese, C. R., Marks, M. J., Logel, J., Adams, C. E., Sullivan, B., Collins, A. C., & Leonard, S. (1997). Effect of smoking history on [3H]nicotine binding in human postmortem brain. Journal of Experimental Therapy, 282, 7–13.Google Scholar
  8. Carlsson, M. L. (1998). Hypothesis: Is infantile autism a hypoglutamatergic disorder? Relevance of glutamate-serotonin interactions for pharmacotherapy. Journal of Neural Transmission, 105, 525–535.PubMedGoogle Scholar
  9. Courchesne, B., Hesselink, J. R., Jernigan, T. L., & Yeung-Courchesne, R. (1987). Abnormal neuroanatomy in a nonretarded person with autism: Unusual findings with magnetic resonance imaging. Archives of Neurology, 44(3), 335–341.PubMedGoogle Scholar
  10. DeLong, G. R., & Heinz, E. R. (1997). The syndrome of early-life bilateral hippocampal sclerosis. Annals of Neurology, 42, 11–17.PubMedGoogle Scholar
  11. Eberwine, J., Yeh, H., Miyashiro, K., Cao, Y., Nair, S., Finnell, R., Zettel, M., & Coleman, P. (1992). Analysis of gene expression in single live neurons. Proceedings of the National Academy of Sciences, 89, 3010–3014.Google Scholar
  12. Gillberg, I. C., Bjure, J., Uvebrant, P., Vestergren, E., & Gillberg, I. C. (1993). SPECT (single photon emission computed tomography) in 31 children and adolescents with autism and autisticlike conditions. European Child and Adolescent Psychiatry, 2, 50–59.Google Scholar
  13. Heath, R. G. (1972). Electroencephalographic studies in isolationraised monkeys with behavioral impairment. Diseases of the Nervous System, 33, 157–163.PubMedGoogle Scholar
  14. Hemby, S. E., Ginsberg, S., Becker, K., Brunk, B., Arnold, S. E., Trojanowski, J. Q., Overton, C., & Eberwine, J. H. (in press). A mRNA expression profile for schizophrenia: Single-neuron transcription pattern in the entorhinal cortex. Archives of General Psychiatry. Google Scholar
  15. Hurd, Y. L., & Herkenham, M. (1993). Molecular alterations in the neostriatum of human cocaine addicts. Synapse, 13, 357–369.PubMedGoogle Scholar
  16. Kish, S. J., Shannak, K., & Hornykiewicz, O. (1988). Uneven pattern of dopamine loss in the striatum of patients with idiopathic Parkinson's disease. Pathophysiologic and clinical implications. New England Journal of Medicine, 31, 876–880.Google Scholar
  17. Little, K. Y., Kirkman, J. A., Carroll, F. I., Breese, G. R., & Duncan, G. E. (1993a). [125I]RTI-55 Binding to cocaine-sensitive dopaminergic and serotonergic uptake sites in the human brain. Journal of Neurochemistry, 61, 1996–2006.PubMedGoogle Scholar
  18. Little, K. Y., Kirkman, J. A., Carroll, F. I., Clark, T. B., & Duncan, G. E. (1993b). Cocaine use increases [3H]WIN 35428 binding sites in human striatum. Brain Research, 628, 17–25.PubMedGoogle Scholar
  19. Mikel, U. V., & Becker, R. L. (1991). A comparative study of quantitative stains for DNA in image cytometry. Analytical Quantitative of Cytologic Histology, 13, 253–260.Google Scholar
  20. Piven, J., Arndt, S., Bailey, J., Havercamp, S., Andreasen, N. C., & Palmer, P. (1995). An MRI study of brain size in autism. American Journal of Psychiatry, 152(8), 1145–1149.PubMedGoogle Scholar
  21. Piven, J., Arndt, S., Bailey, J., & Andreasen, N. (1996). Regional brain enlargement in autism: A magnetic resonance imaging study. Journal of the American Academy of Child and Adolescent Psychiatry, 4, 530–536.Google Scholar
  22. Raymond, G. V., Bauman, M. L., & Kemper, T. L. (1996). Hippocampus in autism: A Golgi analysis. Acta Neuropathologica, 91(1), 117–119.PubMedGoogle Scholar
  23. Rutter, M., Andersen-Wood, L., Beckett, C., Bredenkamp, D., Castle, J., Groothues, C., et al. (1999). Quasi-autistic patterns following severe early global privation. English and Romanian Adoptees (ERA) Study Team. Journal of Child Psychology & Psychiatry & Allied Disciplines, 40(4), 537–549.Google Scholar
  24. Saitoh, O., Courchesne, E., Egaas, B., Lincoln, A. J., & Schreibman, I. (1995). Cross-sectional area of the posterior hippocampus in autistic patients with cerebellar and corpus callosum abnormalities. Neurology, 45(2), 317–324.PubMedGoogle Scholar
  25. Sanchez, M. M., Hearn, E. F., Do, D., Rilling, J. K., & Herndon, J. G. (1998). Differential rearing affects corpus callosum size and cognitive function of rhesus monkeys. Brain Research, 812 (1–2), 38-49.PubMedGoogle Scholar
  26. Siegel, S. J., Ginsberg, S. D., Hof, P. R., Foote, S. L., Young, W. G., Kraemer, G. W., et al. (1993). Effects of social deprivation in prepubescent rhesus monkeys: Immunohistochemical analysis of the neurofilament protein triplet in the hippocampal formation. Brain Research, 619, 299–305.PubMedGoogle Scholar
  27. Staley, J. K., Basile, M., Flynn, D. D., & Mash, D. C. (1994a).Visualization of dopamine and serotonin transporters in the human brain with the potent cocaine analogue [125I]RTI-55: In vitro binding and autoradiographic characterization Journal of Neurochemistry, 62(2), 549–556.PubMedGoogle Scholar
  28. Staley, J. K., Hearn, W. L., Ruttenber, A J., Wetli, C. V., & Mash, D. C. (1994b). High affinity cocaine recognition sites on the dopamine transporter are elevated in fatal cocaine overdose victims. Journal of Pharmacology Experimental Therapy, 271, 1678–1685.Google Scholar
  29. Staley, J. K., Rothman, R. B., Rice, K. C., Partilla, J., & Mash, D. C. (1997). Kappa2 opioid receptors in limbic areas of the human brain are upregulated by cocaine in fatal overdose victims. Neuroscience, 17, 8225–8233.PubMedGoogle Scholar
  30. Tecott, L., Barchas, J., & Eberwine, J. (1988). In situ transcription: Specific synthesis of cDNA in fixed tissue sections. Science, 240, 1661–1664.PubMedGoogle Scholar
  31. Van Gelder, R. N., von Zastrow, M. E., Yool, A., Dement, W. C., Barchas, J. D., & Eberwine, J. H. (1990). Amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proceedings of the National Academy of Sciences USA, 87, 1663–1667.Google Scholar
  32. Van Hoesen, G. W. (1992). The parahippocampal gyrus: New observations regarding its cortical connections in the monkey. Trends in Neuroscience, 5, 345–350.Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Scott E. Hemby
    • 1
    • 2
    • 3
  • Mar M. Sanchez
    • 2
    • 4
  • James T. Winslow
    • 2
    • 4
  1. 1.Department of PharmacologyEmory University School of MedicineAtlanta
  2. 2.Department of Psychiatry and Behavioral SciencesEmory University School of MedicineAtlanta
  3. 3.Division of NeuroscienceYerkes Regional Primate Research CenterAtlanta
  4. 4.Division of PsychobiologyYerkes Regional Primate Research CenterAtlanta

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