Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β
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 β‐pro...
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Online Access: | https://doi.org/10.15252/emmm.201808931 |
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doaj-6042a47b2d4743dcb10dfa26b12af8bc2021-08-02T12:28:52ZengWileyEMBO Molecular Medicine1757-46761757-46842018-09-01109n/an/a10.15252/emmm.201808931Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐βHuixin Xu0Molly M Rajsombath1Pia Weikop2Dennis J Selkoe3Ann Romney Center for Neurologic Diseases Brigham and Women's Hospital & Harvard Medical School Boston MA USAAnn Romney Center for Neurologic Diseases Brigham and Women's Hospital & Harvard Medical School Boston MA USACenter for Translational Neuromedicine University of Copenhagen Copenhagen DenmarkAnn Romney Center for Neurologic Diseases Brigham and Women's Hospital & Harvard Medical School Boston MA USAAbstract 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 β‐protein (oAβ). Mechanistically, we report that the key factor in microglial protection by EE is chronically enhanced β‐adrenergic signaling. Quantifying microglial morphology and inflammatory RNA profiles revealed that mice in standard housing (SH) fed the β‐adrenergic agonist isoproterenol experienced similar protection of microglia against oAβ‐induced inflammation as did mice in EE. Conversely, mice in EE fed the β‐adrenergic antagonist propranolol lost microglial protection against oAβ. Mice lacking β1/β2‐adrenergic receptors showed no protection of microglia by EE. In SH mice, quantification of norepinephrine in hippocampus and interstitial fluid showed that oAβ disrupted norepinephrine homeostasis, and microglial‐specific analysis of β2‐adrenergic receptors indicated a decreased receptor level. Both features were rescued by EE. Thus, enhanced β‐adrenergic signaling at the ligand and receptor levels mediates potent benefits of EE on microglial inflammation induced by human Aβ oligomers in vivo.https://doi.org/10.15252/emmm.201808931Alzheimer's diseaseenvironmental enrichmentmicroglianeuroinflammationβ‐adrenergic signaling |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huixin Xu Molly M Rajsombath Pia Weikop Dennis J Selkoe |
spellingShingle |
Huixin Xu Molly M Rajsombath Pia Weikop Dennis J Selkoe Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β EMBO Molecular Medicine Alzheimer's disease environmental enrichment microglia neuroinflammation β‐adrenergic signaling |
author_facet |
Huixin Xu Molly M Rajsombath Pia Weikop Dennis J Selkoe |
author_sort |
Huixin Xu |
title |
Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β |
title_short |
Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β |
title_full |
Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β |
title_fullStr |
Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β |
title_full_unstemmed |
Enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β |
title_sort |
enriched environment enhances β‐adrenergic signaling to prevent microglia inflammation by amyloid‐β |
publisher |
Wiley |
series |
EMBO Molecular Medicine |
issn |
1757-4676 1757-4684 |
publishDate |
2018-09-01 |
description |
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 β‐protein (oAβ). Mechanistically, we report that the key factor in microglial protection by EE is chronically enhanced β‐adrenergic signaling. Quantifying microglial morphology and inflammatory RNA profiles revealed that mice in standard housing (SH) fed the β‐adrenergic agonist isoproterenol experienced similar protection of microglia against oAβ‐induced inflammation as did mice in EE. Conversely, mice in EE fed the β‐adrenergic antagonist propranolol lost microglial protection against oAβ. Mice lacking β1/β2‐adrenergic receptors showed no protection of microglia by EE. In SH mice, quantification of norepinephrine in hippocampus and interstitial fluid showed that oAβ disrupted norepinephrine homeostasis, and microglial‐specific analysis of β2‐adrenergic receptors indicated a decreased receptor level. Both features were rescued by EE. Thus, enhanced β‐adrenergic signaling at the ligand and receptor levels mediates potent benefits of EE on microglial inflammation induced by human Aβ oligomers in vivo. |
topic |
Alzheimer's disease environmental enrichment microglia neuroinflammation β‐adrenergic signaling |
url |
https://doi.org/10.15252/emmm.201808931 |
work_keys_str_mv |
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