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Senior Investigator

Carolyn Beebe Smith, Ph.D.

Laboratory on Cerebral Metabolism
Building 35 Room 2B1016
35 Convent Drive MSC3702
Bethesda MD 20892-3702
Office: (301) 402-3120

Fax: (301) 480-1668

Dr. Smith received a Ph.D. from the University of London where she studied the chemical pathology of Alzheimer's Disease with David Bowen, for which she was awarded the Queen Square Prize. She did postdoctoral training with Louis Sokoloff at NIMH and in 1986 became a Senior Investigator within the Laboratory of Cerebral Metabolism, NIMH. In 2000 Dr. Smith was awarded an honorary degree from the University of Link�ping for her work developing an in vivo quantitative autoradiographic method for regional rates of cerebral protein synthesis in experimental animals. Dr Smith's group is currently studying the mechanisms of brain dysfunction in genetic mouse models of inherited forms of mental retardation.

The purpose of the Unit on Neurobiology is to investigate the causes of hereditary mental retardation, with the goal of developing effective treatments for these disorders and furthering our understanding of the molecular bases of learning and memory. Particular areas of interest include phenylketonuria (a disease of phenylalanine metabolism) and fragile X syndrome (a CGG repeat disease in which the synthesis of a specific protein is suppressed). Mechanisms underlying behavioral impairments are studied in genetic mouse models of the diseases. One of the tools used in these investigations is a quantitative autoradiographic method developed by our group for the in vivo measurement of regional rates of cerebral protein synthesis. Another research goal of our group is the adaptation and validation of this method for use in man with positron emission tomography. We expect that this method will be an invaluable clinical tool for diagnosis and assessment of efficacy of treatments in developmental and degenerative disorders of the nervous system.

Cerebral Protein Synthesis in a Genetic Mouse Model of Phenylketonuria

Figure illustrates decreased rates of cerebral protein synthesis in mice homozygous for a mutation in the gene for phenylalanine hydroxylase.

Digitized autoradiograms of coronal sections at three different levels in brain from mice representative of the three genotypes studied: BTBR, background control; HTZ, heterozygous for PKU mutation; HMZ, homozygous for PKU mutation. Images have been color-coded for lCPSleu (rates of leucine incorporation into protein). Sections illustrated were taken at the levels of the prelimbic cortex (top row), dorsal hippocampus (second row), and cerebellum (bottom row). The color bar (right) provides the calibration scale for the range of values of lCPSleu in nmol.g-1.min-1 for each color. Dorsal side is top; right side is on right. Bar (lower right) = 5 mm.

Staff Image
  • Thomas Burlin, B.S.
    Research Assistant
    (301) 496-6901

  • Julia Kang, B.S.
    Research Assistant
    (301) 402-3121

  • Mei Qin, Ph.D.
    Postdoctoral Fellow
    (301) 402-3123

  • 1) Qin M Kang J Smith CB (2002)
  • Increased rates of cerebral glucose metabolism in a mouse model of fragile X mental retardation.
  • Proc Natl Acad Sci U S A, 99, 15758-63
  • 2) Smith CB Kang J (2000)
  • Cerebral protein synthesis in a genetic mouse model of phenylketonuria.
  • Proc Natl Acad Sci U S A, 97, 11014-9
  • 3) Melzer P Smith CB (1998)
  • Plasticity of cerebral metabolic whisker maps in adult mice after whisker follicle removal--I. Modifications in barrel cortex coincide with reorganization of follicular innervation.
  • Neuroscience, 83, 27-41
  • 4) Frerichs KU Smith CB Brenner M DeGracia DJ Krause GS Marrone L Dever TE Hallenbeck JM (1998)
  • Suppression of protein synthesis in brain during hibernation involves inhibition of protein initiation and elongation.
  • Proc Natl Acad Sci U S A, 95, 14511-6
  • 5) Nakanishi H Sun Y Nakamura RK Mori K Ito M Suda S Namba H Storch FI Dang TP Mendelson W Mishkin M Kennedy C Gillin JC Smith CB Sokoloff L (1997)
  • Positive correlations between cerebral protein synthesis rates and deep sleep in Macaca mulatta.
  • Eur J Neurosci, 9, 271-9
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