The Medial Septum Is Insulin Resistant in the AD Presymptomatic Phase: Rescue by Nerve Growth Factor-Driven IRS1 Activation.

ABSTRACT: Basal forebrain cholinergic neurons (BFCN) are key modulators of learning and memory and are high energy-demanding neurons. Impaired neuronal metabolism and reduced insulin signaling, known as insulin resistance, has been reported in the early phase of Alzheimer's disease (AD), which has been suggested to be "Type 3 Diabetes." We hypothesized that BFCN may develop insulin resistance and their consequent failure represents one of the earliest event in AD. We found that a condition reminiscent of insulin resistance occurs in the medial septum of 3 months old 3×Tg-AD mice, reported to develop typical AD histopathology and cognitive deficits in adulthood. Further, we obtained insulin resistant BFCN by culturing them with high insulin concentrations. By means of these paradigms, we observed tha

SUBMITTER: Sposato V 

PROVIDER: S-EPMC6334735 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature