- Title
- Insensitivity of astrocytes to interleukin 10 signaling following peripheral immune challenge results in prolonged microglial activation in the aged brain
- Creator
- Norden, Diana M.; Trojanowski, Paige J.; Walker, Frederick R.; Godbout, Jonathan P.
- Relation
- Neurobiology of Aging Vol. 44, Issue August 2016, p. 22-41
- Publisher Link
- http://dx.doi.org/10.1016/j.neurobiolaging.2016.04.014
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2016
- Description
- Immune-activated microglia from aged mice produce exaggerated levels of cytokines. Despite high levels of microglial interleukin (IL)-10 in the aged brain, neuroinflammation was prolonged and associated with depressive-like deficits. Because astrocytes respond to IL-10 and, in turn, attenuate microglial activation, we investigated if astrocyte-mediated resolution of microglial activation was impaired with age. Here, aged astrocytes had a dysfunctional profile with higher glial fibrillary acidic protein, lower glutamate transporter expression, and significant cytoskeletal re-arrangement. Moreover, aged astrocytes had reduced expression of growth factors and IL-10 receptor-1 (IL-10R1). After in vivo lipopolysaccharide immune challenge, aged astrocytes had a molecular signature associated with reduced responsiveness to IL-10. This IL-10 insensitivity of aged astrocytes resulted in a failure to induce IL-10R1 and transforming growth factor β and resolve microglial activation. In addition, adult astrocytes reduced microglial activation when co-cultured ex vivo, whereas aged astrocytes did not. Consistent with the aging studies, IL-10RKO astrocytes did not augment transforming growth factor β after immune challenge and failed to resolve microglial activation. Collectively, a major cytokine-regulatory loop between activated microglia and astrocytes is impaired in the aged brain.
- Subject
- astrocyte; microglia; aging; neuroinflammation; interleukin-10; TGF-beta
- Identifier
- http://hdl.handle.net/1959.13/1324072
- Identifier
- uon:24954
- Identifier
- ISSN:0197-4580
- Language
- eng
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