Brian Shonesy
Last active: 7/2/2015

Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents.

Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V
Neurobiol Aging. 2012 33 (2): 430.e5-18

PMID: 21256630 · DOI:10.1016/j.neurobiolaging.2010.12.002

To better understand the role of insulin signaling in the development of Alzheimer's disease (AD), we utilized an animal model (intracerebroventricular injection of streptozotocin-ic-streptozotocin (STZ)) that displays insulin resistance only in the brain and exhibits AD pathology. In this model, deficits in hippocampal synaptic transmission and long-term potentiation (LTP) were observed. The decline in LTP correlated with decreased expression of NMDAR subunits NR2A and NR2B. The deficits in LTP were accompanied by changes in the expression and function of synaptic AMPARs. In ic-STZ animals, an alteration in integrin-linked kinase (ILK)-glycogen synthase kinase 3 beta (GSK-3-β) signaling was identified (p < 0.05). Similarly, there was decreased expression (p < 0.05) of brain derived neurotropic factor (BDNF) and stargazin, an AMPAR auxiliary subunit; both are required for driving AMPA receptors to the surface of the postsynaptic membrane. Our data illustrate that altered ILK-GSK-3β signaling due to impaired insulin signaling may decrease the trafficking and function of postsynaptic glutamate receptors; thereby, leading to synaptic deficits contributing to memory loss.

Copyright © 2012 Elsevier Inc. All rights reserved.

MeSH Terms (14)

Alzheimer Disease Animals Brain Humans Injections, Intraventricular Insulin Resistance Long-Term Potentiation Male Rats Rats, Wistar Receptors, Glutamate Streptozocin Synapses Synaptic Transmission

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