摘要

Recent studies have suggested that cortical astroglia play an important role in depressive-like behaviors. Potential astroglial contributions have been proposed based on their known neuroplastic functions, such as glutamate recycling and synaptic plasticity. However, the specific mechanisms by which astroglial cells may contribute or protect against a depressive phenotype remain unknown. To delineate astroglial changes that accompany depressive-like behavior, we used astroglial-specific bacTRAP mice exposed to chronic variable stress (CVS) and profiled the astroglial translatome using translating ribosome affinity purification (TRAP) in conjunction with RNAseq. As expected, CVS significantly increased anxiety- and depressive-like behaviors and corticosterone levels and decreased GFAP expression in astroglia, although this did not reflect a change in the total number of astroglial cells. TRAPseq results showed that CVS decreased genes associated with astroglial plasticity: RhoGTPases, growth factor signaling, and transcription regulation, and increased genes associated with the formation of extracellular matrices such as perineuronal nets (PNNs). PNNs inhibit neuroplasticity and astroglia contribute to the formation, organization, and maintenance of PNNs. To validate our TRAPseq findings, we showed an increase in PNNs following CVS. Degradation of PNNs in the prefrontal cortex of mice exposed to CVS reversed the CVS-induced behavioral phenotype in the forced swim test. These data lend further support to the neuroplasticity hypothesis of depressive behaviors and, in particular, extend this hypothesis beyond neuronal plasticity to include an overall decrease in genes associated with cortical astroglial plasticity following CVS. Further studies will be needed to assess the antidepressant potential of directly targeting astroglial cell function in models of depression.

译文

最近的研究表明,皮质星形胶质细胞在抑郁样行为中发挥重要作用。基于它们已知的神经可塑性功能,如谷氨酸再循环和突触可塑性,已经提出了潜在的星形胶质细胞贡献。然而,星形胶质细胞可能有助于或保护对抗抑郁表型的具体机制仍然未知。为了描绘伴随抑郁样行为的星形胶质细胞变化,我们使用了暴露于慢性可变压力 (CVS) 的星形胶质细胞特异性 bacTRAP 小鼠,并使用翻译核糖体亲和纯化 (TRAP) 对星形胶质细胞转体进行了描述结合 RNAseq。不出所料,CVS 显著增加焦虑和抑郁样行为以及皮质酮水平,并降低星形胶质细胞中 GFAP 的表达,尽管这并没有反映星形胶质细胞总数的变化。TRAPseq 结果显示,CVS 减少了与星形胶质可塑性相关的基因: RhoGTPases 、生长因子信号传导和转录调控,并增加了与细胞外基质如神经周围网 (PNNs) 形成相关的基因。PNNs 抑制神经可塑性,星形胶质细胞有助于 PNNs 的形成、组织和维持。为了验证我们的 TRAPseq 发现,我们展示了在 CVS 之后 PNNs 的增加。暴露于 CVS 的小鼠前额皮质中 PNNs 的降解逆转了强迫游泳试验中 CVS 诱导的行为表型。这些数据进一步支持抑郁行为的神经可塑性假说,特别是,将这一假说扩展到神经元可塑性之外,包括 CVS 后与皮质星形胶质可塑性相关的基因总体下降。需要进一步的研究来评估抑郁症模型中直接靶向星形胶质细胞功能的抗抑郁潜力。

Astroglial

内分泌 细胞 临床研究术语
概述  :  

星形胶质细胞是在脑和脊髓中的特性星形胶质细胞。大脑中星形胶质细胞的比例尚不明确。根据所使用的计数技术,研究发现星形胶质细胞的比例随区域而异,占所有神经胶质细胞的 20%至40%。它们执行许多功能,包括形成内皮细胞、血脑屏障,为神经组织提供营养,维持细胞外离子平衡,以及在创伤后脑和脊髓的修复和瘢痕形成过程中发挥作用。结构星形胶质细胞是中枢神经系统中神经胶质细胞的一种亚型,呈星形,它们的许多过程都包裹着神经元产生的突触。传统上使用组织学分析鉴定星形胶质细胞。这些细胞中的许多表达中间丝状神经胶质原

astroglial

释    义   n. 星状胶质细胞

例    句   Astroglial cells or astrocytes are specialized cells that support neuron function with nutrients and protective buffering.星形胶质细胞是一种特殊细胞,它能够通过释放营养素和缓冲保护作用支持神经元的功能。

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