Age-associated cholesterol reduction triggers brain insulin resistance by facilitating ligand-independent receptor activation and pathway desensitization.

ABSTRACT: In the brain, insulin plays an important role in cognitive processes. During aging, these faculties decline, as does insulin signaling. The mechanism behind this last phenomenon is unclear. In recent studies, we reported that the mild and gradual loss of cholesterol in the synaptic fraction of hippocampal neurons during aging leads to a decrease in synaptic plasticity evoked by glutamate receptor activation and also by receptor tyrosine kinase (RTK) signaling. As insulin and insulin growth factor activity are dependent on tyrosine kinase receptors, we investigated whether the constitutive loss of brain cholesterol is also involved in the decay of insulin function with age. Using long-term depression (LTD) induced by application of insulin to hippocampal slices as a read-out, we found that

SUBMITTER: Martin-Segura A 

PROVIDER: S-EPMC6516156 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature