The Aging Astrocyte Transcriptome from Multiple Regions of the Mouse Brain.
The Aging Astrocyte Transcriptome from Multiple Regions of the Mouse Brain.
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来自小鼠大脑多个区域的老化星形胶质细胞转录组。
DOI：
10.1016/j.celrep.2017.12.039
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发表时间：
2018-01-02
期刊：
影响因子：
8.8
通讯作者：
Allen NJ
中科院分区：
文献类型：
--
作者：
Boisvert MM;Erikson GA;Shokhirev MN;Allen NJ
衰老的大脑经历认知能力下降，与神经元突触数量和功能减少以及代谢改变有关。星形胶质细胞在发育和成年期调节神经元突触的形成和功能，但这些特性是否在衰老过程中发生变化，导致神经元功能障碍，目前尚不清楚。我们通过从多个小鼠大脑区域产生老年和成年星形胶质细胞转录组来解决这个问题。这些数据提供了一个全面的成人和老年星形胶质细胞基因表达的RNA-seq数据库，可在线作为资源。我们确定了星形胶质细胞基因的改变，通过大脑区域的老化和区域独特的老化变化。老化的星形胶质细胞显示出体内平衡和神经传递调节基因的微小改变。然而，老化的星形胶质细胞上调消除突触的基因，部分类似于反应性星形胶质细胞。我们进一步确定了不同皮质区域星形胶质细胞之间突触调节基因的异质性表达。我们发现，老化过程中星形胶质细胞的改变创造了一个允许突触消除和神经元损伤的环境，可能导致与衰老相关的认知能力下降。衰老的大脑减少了突触数量，神经元活动减少，功能由邻近的星形胶质细胞调节。Boisvert等人研究了老化的星形胶质细胞是否对这些变化有贡献，发现老化的星形胶质细胞显示炎症和突触消除途径的基因表达增加，胆固醇合成酶减少。
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. The aging brain has reduced synapse number and decreased neuronal activity, functions regulated by neighboring astrocytes. Boisvert et al. investigated if aging astrocytes are contributing to these changes and found that aged astrocytes show increased expression of genes for inflammatory and synapse elimination pathways and decreased cholesterol synthesis enzymes.
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影响因子：
4.3
作者：
Goodman T;Hajihosseini MK
通讯作者：
Hajihosseini MK
影响因子：
9.3
作者：
Cribbs DH;Berchtold NC;Perreau V;Coleman PD;Rogers J;Tenner AJ;Cotman CW
通讯作者：
Cotman CW
影响因子：
4.2
作者：
Pelvig, D. P.;Pakkenberg, H.;Pakkenberg, B.
通讯作者：
Pakkenberg, B.
影响因子：
56.9
作者：
Huh, GS;Boulanger, LM;Shatz, CJ
通讯作者：
Shatz, CJ
DOI：
10.1007/s00018-017-2572-3
发表时间：
2017-11
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Peek SL;Mah KM;Weiner JA
通讯作者：
Weiner JA