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      Functional characterization of Des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampus

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      Author
      Ramsey, M. M.
      Adams, Michelle M.
      Ariwodola, O. J.
      Sonntag, W. E.
      Weiner, J.
      Date
      2005
      Source Title
      Journal of Neurophysiology
      Print ISSN
      0022-3077
      Electronic ISSN
      1522-1598
      Publisher
      American Physiological Society
      Volume
      94
      Issue
      1
      Pages
      247 - 254
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      Insulin-like growth factor-1 (IGF-1) and growth hormone play a major role in the growth and development of tissues throughout the mammalian body. Plasma IGF-1 concentrations peak during puberty and decline with age. We have determined that chronic treatments to restore plasma IGF-1 concentrations to adult levels attenuate spatial learning deficits in aged rats, but little is known of the acute actions of IGF-1 in the brain. To this end, we utilized hippocampal slices from young Sprague-Dawley rats to characterize the acute effects of des-IGF-1 on excitatory synaptic transmission in the CA1 region. We observed a 40% increase in field excitatory postsynaptic potential (fEPSP) slope with application of des-IGF-1 (40 ng/ml) and used whole cell patch-clamp recordings to determine that this enhancement was due to a postsynaptic mechanism involving α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate (AMPA) but not N-methyl-d-aspartate receptors. Furthermore, the enhancement was completely blocked by the broad-spectrum tyrosine kinase inhibitor, genistein (220 μM), and significantly reduced by the PI3K blockers wortmannin (1 μM) and 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (10 μM), suggesting that the effect was predominantly dependent on PI3K activation. This characterization of the acute actions of des-IGF-1 at hippocampal excitatory synapses may provide insight into the mechanism by which long-term increases in plasma IGF-1 impart cognitive benefits in aged rats. Increases in AMPA receptor-mediated synaptic transmission may contribute directly to cognitive improvement or initiate long-term changes in synthesis of proteins such as brain-derived neurotrophic factor that are important to learning and memory.
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      http://hdl.handle.net/11693/53542
      Published Version (Please cite this version)
      https://doi.org/10.1152/jn.00768.2004
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