Transcriptomic and functional studies reveal undermined chemotactic and angiostimulatory properties of aged microglia during stroke recovery. Issue 1 (December 2020)

• Record Type: Journal Article
• Authors: Jiang, Lu; Mu, Hongfeng; Xu, Fei; Xie, Di; Su, Wei; Xu, Jing; Sun, Zeyu; Liu, Silvia; Luo, Jianhua; Shi, Yejie; Leak, Rehana K; Wechsler, Lawrence R; Chen, Jun; Hu, Xiaoming
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 40:Issue 1(2020)Supplement
• Page Start: S81
• Page End: S97
• Publication Date: 2020-12
• Subjects: Microglia -- aging -- cell movement -- angiogenesis -- transcriptome; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1177/0271678X20902542
• Languages: English
• ISSNs: 0271-678X

Abstract

Age-dependent alterations in microglia behavior have been implicated in neurodegeneration and CNS injuries. Here, we compared the transcriptional profiles of young versus aged microglia during stroke recovery. CD45 intermediate CD11b + microglia were FACS-isolated from the brains of young (10-week-old) and aged (18-month-old) male mice with sham operation or 14 days after distal middle cerebral artery occlusion and subjected to RNA-sequencing analysis. Functional groups enriched in young microglia are indicative of upregulation in cell movement, cell interactions, inflammatory responses and angiogenesis, while aged microglia exhibited a reduction or no change in these features. We confirmed reduced chemoattractive capacities of aged microglia toward ischemic brain tissue in organotypic slide co-cultures, and delayed accumulation of aged microglia around dead neurons injected into the striatum in vivo . In addition, aging is associated with an overall failure to increase the expression of microglial genes involved in cell–cell interactions, such as CXCL10. Finally, impaired upregulation of pro-angiogenic genes in aged microglia was associated with a decline in neovascularization in aged mice compared to young mice after distal middle cerebral artery occlusion. This study provides a new resource to understand the mechanisms underlying microglial alterations in the aged brain milieu and sheds light on new strategies to improve microglial functions in aged stroke victims.