Functional characterization of Des-IGF-1 action at excitatory synapses in the CA1 region of rat hippocampus
Author
Ramsey, M. M.
Adams, Michelle M.
Ariwodola, O. J.
Sonntag, W. E.
Weiner, J.
Date
2005Source 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
ArticleItem 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.