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The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function

  1. Author:
    Egan, M. F.
    Kojima, M.
    Callicott, J. H.
    Goldberg, T. E.
    Kolachana, B. S.
    Bertolino, A.
    Zaitsev, E.
    Gold, B.
    Goldman, D.
    Dean, M.
    Lu, B.
    Weinberger, D. R.

  2. Author Address

    NICHHD, Sect Neural Dev & Plast, NIH, DHHS, Bldg 49-6A67, Bethesda, MD 20892 USA NICHHD, Sect Neural Dev & Plast, NIH, DHHS, Bethesda, MD 20892 USA NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA NIAAA, Neurogenet Lab, Rockville, MD 20857 USA NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA Natl Inst AIST, Cell Dynam Res Grp, Osaka 5638577, Japan Japan Sci & Technol Corp, CREST, Kawaguchi 3320012, Japan Lu B NICHHD, Sect Neural Dev & Plast, NIH, DHHS, Bldg 49-6A67, Bethesda, MD 20892 USA
    1. Year: 2003
  2. Journal: Cell
    1. 112
    2. 2
    3. Pages: 257-269
  4. Type of Article: Article
  1. Abstract:

    Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity and hippocampal-dependent memory in cell models and in animals. We examined the effects of a valine (val) to methionine (met) substitution in the 5' pro-region of the human BDNF protein. In human subjects, the met allele was associated with poorer episodic memory, abnormal hippocampal activation assayed with fMRI, and lower hippocampal n-acetyl aspartate (NAA), assayed with MRI spectroscopy. Neurons transfected with met-BDNF-GFP showed lower depolarization-induced secretion, while constitutive secretion was unchanged. Furthermore, met- BDNF-GFP failed to localize to secretory granules or synapses. These results demonstrate a role for BDNF

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