Environmental novelty activates ?2-adrenergic signaling to prevent the impairment of hippocampal LTP by A? oligomers.

ABSTRACT: A central question about human brain aging is whether cognitive enrichment slows the development of Alzheimer changes. Here, we show that prolonged exposure to an enriched environment (EE) facilitated signaling in the hippocampus of wild-type mice that promoted long-term potentiation. A key feature of the EE effect was activation of ?2-adrenergic receptors and downstream cAMP/PKA signaling. This EE pathway prevented LTP inhibition by soluble oligomers of amyloid ?-protein (A?) isolated from AD cortex. Protection by EE occurred in both young and middle-aged wild-type mice. Exposure to novelty afforded greater protection than did aerobic exercise. Mice chronically fed a ?-adrenergic agonist without EE were protected from hippocampal impairment by A? oligomers. Thus, EE enhances hippocampal synaptic plasticity by activating ?-adrenoceptor signaling and mitigating synaptotoxicity of human A? oligomers. These mechanistic insights support using prolonged exposure to cognitive novelty and/or oral ?-adrenergic agonists to lessen the effects of A? accumulation during aging.

SUBMITTER: Li S 

PROVIDER: S-EPMC3596823 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature