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In vivo restoration of physiological levels of truncated TrkB.T1 receptor rescues neuronal cell death in a trisomic mouse model

  1. Author:
    Dorsey, S. G.
    Renn, C. L.
    Carim-Todd, L.
    Barrick, C. A.
    Bambrick, L.
    Krueger, B. K.
    Ward, C. W.
    Tessarollo, L.

  2. Author Address

    NCI, Ctr Canc Res, Mouse Canc Genet Program, Neural Dev Grp, Frederick, MD 21702 USA. Univ Maryland, Sch Med, Sch Nursing, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.;Dorsey, SG, NCI, Ctr Canc Res, Mouse Canc Genet Program, Neural Dev Grp, Frederick, MD 21702 USA.;sdorsey@son.umaryland.edu tessarol@ncifcrf.gov
    1. Year: 2006
    2. Date: Jul
  2. Journal: Neuron
    1. 51
    2. 1
    3. Pages: 21-28
  4. Type of Article: Article
  5. ISSN: 0896-6273
  1. Abstract:

    Imbalances in neurotrophins or their high-affinity Trk receptors have long been reported in neurodegenerative diseases. However, a molecular link between these gene products and neuronal cell death has not been established. In the trisomy 16 (Ts16) mouse there is increased apoptosis in the cortex, and hippocampal neurons undergo accelerated cell death that cannot be rescued by administration of brain-derived neurotrophic factor (BDNF). Ts16 neurons have normal levels of the TrkB tyrosine kinase receptor but an upregulation of the TrkB.T1 truncated receptor isoform. Here we show that restoration of the physiological level of the TrkB.T1 receptor by gene targeting rescues Ts16 cortical cell and hippocampal neuronal death. Moreover, it corrects resting Ca2+ levels and restores BDNF-induced intracellular signaling mediated by full-length TrkB in Ts16 hippocampal neurons. These data provide a direct link between neuronal cell death and abnormalities in Trk neurotrophin receptor levels.

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  1. View record in Web of Science®
  2. WOS: 000239037700007

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