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

Abstract 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...

Full description

Saved in:
Bibliographic Details
Published in:Neurobiology of aging 2012-02, Vol.33 (2), p.430.e5-430.e18
Main Authors: Shonesy, Brian C, Thiruchelvam, Kariharan, Parameshwaran, Kodeeswaran, Rahman, Engy Abdel, Karuppagounder, Senthilkumar S, Huggins, Kevin W, Pinkert, Carl A, Amin, Rajesh, Dhanasekaran, Muralikrishnan, Suppiramaniam, Vishnu
Format: Article
Language:English
Subjects:
Alzheimer Disease - chemically induced
Alzheimer Disease - physiopathology
Alzheimer's disease
AMPAR
Animals
Brain - drug effects
Brain - physiopathology
Hippocampus
Humans
ic-STZ
Injections, Intraventricular
Insulin Resistance
Internal Medicine
Long-Term Potentiation
Long-term potentiation (LTP)
Male
Neurology
NMDAR
Rats
Rats, Wistar
Receptors, Glutamate - metabolism
Streptozocin - administration & dosage
Synapses
Synaptic plasticity
Synaptic Transmission
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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.
ISSN:0197-4580
1558-1497
DOI:10.1016/j.neurobiolaging.2010.12.002