Synergistic Trophic Actions on Rat Basal Forebrain Neurons Revealed by a Synthetic NGF/BDNF Chimaeric Molecule

Authors

  • W. J. Friedman,

    Corresponding author
    1. Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, 75 Hoes Lane, CABM 327, Piscataway, NJ, USA
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  • I. B. Black,

    1. Department of Neuroscience and Cell Biology, UMDNJ/Robert Wood Johnson Medical School, 75 Hoes Lane, CABM 327, Piscataway, NJ, USA
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  • H. Persson,

    1. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
    2. Deceased 16 May 1993
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  • C. F. Ibáñez

    1. Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden
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Dr Wilma I. Friedman, as above

Abstract

Basal forebrain cholinergic neurons, which degenerate in Alzheimer's disease, respond to multiple trophic factors, including the neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). This dual responsiveness prompted us to investigate the effects of a synthetic chimaeric molecule, containing the active domains of both NGF and BDNF. The NGF/BDNF chimaeric factor exhibited synergistic actions, and was 100-fold more potent than wild-type BDNF in enhancing survival of cultured dissociated basal forebrain cholinergic neurons. This effect was apparently due to true BDNF/NGF synergy, since addition of the two wild-type trophins simultaneously reproduced the effect of the chimaera. Synergy was selective for neurons which respond to both factors; substantia nigra dopaminergic neurons, which respond to BDNF but not NGF, exhibited no potentiation. The chimaeric factor thus revealed a synergy that may normally occur in the brain, and constitutes a potentially novel therapeutic agent with greater potency than naturally occurring individual trophins.

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