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

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buir.contributor.authorAdams, Michelle M.
dc.citation.epage254en_US
dc.citation.issueNumber1en_US
dc.citation.spage247en_US
dc.citation.volumeNumber94en_US
dc.contributor.authorRamsey, M. M.en_US
dc.contributor.authorAdams, Michelle M.en_US
dc.contributor.authorAriwodola, O. J.en_US
dc.contributor.authorSonntag, W. E.en_US
dc.contributor.authorWeiner, J.en_US
dc.date.accessioned2020-04-05T14:26:06Z
dc.date.available2020-04-05T14:26:06Z
dc.date.issued2005
dc.departmentAysel Sabuncu Brain Research Center (BAM)en_US
dc.description.abstractInsulin-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.en_US
dc.description.provenanceSubmitted by Onur Emek (onur.emek@bilkent.edu.tr) on 2020-04-05T14:26:06Z No. of bitstreams: 1 Functional_Characterization_of_Des-IGF-1_Action_at_Excitatory_Synapses_in.pdf: 285534 bytes, checksum: db9f1a156324acd665870ca4111ddfd7 (MD5)en
dc.description.provenanceMade available in DSpace on 2020-04-05T14:26:06Z (GMT). No. of bitstreams: 1 Functional_Characterization_of_Des-IGF-1_Action_at_Excitatory_Synapses_in.pdf: 285534 bytes, checksum: db9f1a156324acd665870ca4111ddfd7 (MD5) Previous issue date: 2005en
dc.identifier.doi10.1152/jn.00768.2004en_US
dc.identifier.eissn1522-1598
dc.identifier.issn0022-3077
dc.identifier.urihttp://hdl.handle.net/11693/53542
dc.language.isoEnglishen_US
dc.publisherAmerican Physiological Societyen_US
dc.relation.isversionofhttps://doi.org/10.1152/jn.00768.2004en_US
dc.source.titleJournal of Neurophysiologyen_US
dc.titleFunctional characterization of Des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampusen_US
dc.typeArticleen_US

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