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 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 p