Enriched environment enhances ?-adrenergic signaling to prevent microglia inflammation by amyloid-?.

ABSTRACT: Environmental enrichment (EE) is a rodent behavioral paradigm that can model the cognitive benefits to humans associated with intellectual activity and exercise. We recently discovered EE's anti-inflammatory protection of brain microglia against soluble oligomers of human amyloid ?-protein (oA?). Mechanistically, we report that the key factor in microglial protection by EE is chronically enhanced ?-adrenergic signaling. Quantifying microglial morphology and inflammatory RNA profiles revealed that mice in standard housing (SH) fed the ?-adrenergic agonist isoproterenol experienced similar protection of microglia against oA?-induced inflammation as did mice in EE Conversely, mice in EE fed the ?-adrenergic antagonist propranolol lost microglial protection against oA?. Mice lacking ?1/?2-adrenergic receptors showed no protection of microglia by EE In SH mice, quantification of norepinephrine in hippocampus and interstitial fluid showed that oA? disrupted norepinephrine homeostasis, and microglial-specific analysis of ?2-adrenergic receptors indicated a decreased receptor level. Both features were rescued by EE Thus, enhanced ?-adrenergic signaling at the ligand and receptor levels mediates potent benefits of EE on microglial inflammation induced by human A? oligomers in vivo.

SUBMITTER: Xu H 

PROVIDER: S-EPMC6127891 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature