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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2018-08-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.201808931 |
| _version_ | 1827015143489273856 |
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| author | Huixin Xu Molly M Rajsombath Pia Weikop Dennis J Selkoe |
| author_facet | Huixin Xu Molly M Rajsombath Pia Weikop Dennis J Selkoe |
| author_sort | Huixin Xu |
| collection | DOAJ |
| 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. |
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| format | Article |
| id | doaj.art-6042a47b2d4743dcb10dfa26b12af8bc |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:17:52Z |
| publishDate | 2018-08-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-6042a47b2d4743dcb10dfa26b12af8bc2024-10-28T08:57:05ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842018-08-0110911710.15252/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 SchoolAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital & Harvard Medical SchoolCenter for Translational Neuromedicine, University of CopenhagenAnn Romney Center for Neurologic Diseases, Brigham and Women's Hospital & Harvard Medical SchoolAbstract 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 |
| 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 |
| title | 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_short | 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 |
| topic | Alzheimer's disease environmental enrichment microglia neuroinflammation β‐adrenergic signaling |
| url | https://doi.org/10.15252/emmm.201808931 |
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