The Aging Astrocyte Transcriptome from Multiple Regions of the Mouse Brain

被引：496
作者：
Boisvert, Matthew M. [1 ,3 ]
Erikson, Galina A. [2 ]
Shokhirev, Maxim N. [2 ]
Allen, Nicola J. [1 ]
机构：
[1] Salk Inst Biol Studies, Mol Neurobiol Lab, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA
[2] Salk Inst Biol Studies, Razavi Newman Integrat Genom & Bioinformat Core, 10010 North Torrey Pines Rd, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Neurosci Grad Program, La Jolla, CA 92093 USA
来源：
CELL REPORTS | 2018年 / 22卷 / 01期
关键词：
CNS SYNAPTOGENESIS; SYNAPSE ELIMINATION; SECRETED PROTEINS; NEURAL CIRCUITS; AGED MICE; EXPRESSION; RNA; CHOLESTEROL; HIPPOCAMPUS; PLASTICITY;
D O I：
10.1016/j.celrep.2017.12.039
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Aging brains undergo cognitive decline, associated with decreased neuronal synapse number and function and altered metabolism. Astrocytes regulate neuronal synapse formation and function in development and adulthood, but whether these properties change during aging, contributing to neuronal dysfunction, is unknown. We addressed this by generating aged and adult astrocyte transcriptomes from multiple mouse brain regions. These data provide a comprehensive RNA-seq database of adult and aged astrocyte gene expression, available online as a resource. We identify astrocyte genes altered by aging across brain regions and regionally unique aging changes. Aging astrocytes show minimal alteration of homeostatic and neurotransmission-regulating genes. However, aging astrocytes upregulate genes that eliminate synapses and partially resemble reactive astrocytes. We further identified heterogeneous expression of synapse-regulating genes between astrocytes from different cortical regions. We find that alterations to astrocytes in aging create an environment permissive to synapse elimination and neuronal damage, potentially contributing to aging-associated cognitive decline.
引用
收藏
页码：269 / 285
页数：17
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[1]   Astrocyte Regulation of Synaptic Behavior [J].
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Agah, A ;
Lawler, J ;
Mosher, DF ;
Bornstein, P ;
Barres, BA .
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Thompson, Andrew ;
Chen, Chinfei ;
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Henley, William ;
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