内侧前额叶皮层中的成熟星形胶质细胞是删除后星形胶质细胞再填充的来源:对抑郁症的启示

IF 5.4 2区 医学 Q1 NEUROSCIENCES Glia Pub Date : 2024-05-27 DOI:10.1002/glia.24573
Yi-Wen Fu, Shi-Yang Jin, Jing-Ting Li, Xiao-Wen Li, Tian-Ming Gao, Jian-Ming Yang
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引用次数: 0

摘要

成人大脑中的星形胶质细胞在缺失后仍具有很高的再填充能力,新皮质中的成熟星形胶质细胞和神经源区域的神经干细胞都具有生成星形胶质细胞的潜能。然而,缺失后重新增殖的星形胶质细胞的来源和增殖动态在很大程度上仍不清楚。抑郁症患者内侧前额叶皮层(mPFC)中的星形胶质细胞数量减少,选择性地消除 mPFC 星形胶质细胞足以诱发啮齿类动物的抑郁样行为。然而,抑郁症患者的星形胶质细胞再填充能力是否受损尚不清楚。在这项研究中,我们利用不同的转基因小鼠品系对不同类型的细胞进行了基因标记,结果表明,在正常成年雌雄小鼠的 mPFC 中,成熟的星形胶质细胞是星形胶质细胞特异性毒素 L-α-氨基己二酸(L-AAA)诱导的急性缺失后星形胶质细胞再填充的主要来源,并且星形胶质细胞在两周内完成再生,并伴随着抑郁样行为的逆转。此外,重新填充后的 mPFC 星形胶质细胞再消融也会导致抑郁样行为再次出现。对成年雄性小鼠进行为期14天的慢性束缚应激(这是一种经过验证的抑郁症小鼠模型)后,mPFC星形胶质细胞的数量会减少;然而,在L-AAA诱导的删除后,mPFC星形胶质细胞的再增殖能力基本没有改变。我们的研究强调了星形胶质细胞再增殖在抑郁症中的潜在有益作用,并为增强抑郁症局部成熟星形胶质细胞的生成提供了新的治疗见解。
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Mature astrocytes as source for astrocyte repopulation after deletion in the medial prefrontal cortex: Implications for depression

The adult brain retains a high repopulation capacity of astrocytes after deletion, and both mature astrocytes in the neocortex and neural stem cells in neurogenic regions possess the potential to generate astrocytes. However, the origin and the repopulation dynamics of the repopulating astrocytes after deletion remain largely unclear. The number of astrocytes is reduced in the medial prefrontal cortex (mPFC) of patients with depression, and selective elimination of mPFC astrocytes is sufficient to induce depression-like behaviors in rodents. However, whether astrocyte repopulation capacity is impaired in depression is unknown. In this study, we used different transgenic mouse lines to genetically label different cell types and demonstrated that in the mPFC of normal adult mice of both sexes, mature astrocytes were a major source of the repopulating astrocytes after acute deletion induced by an astrocyte-specific toxin, L-alpha-aminoadipic acid (L-AAA), and astrocyte regeneration was accomplished within two weeks accompanied by reversal of depression-like behaviors. Furthermore, re-ablation of mPFC astrocytes post repopulation led to reappearance of depression-like behaviors. In adult male mice subjected to 14-day chronic restraint stress, a well-validated mouse model of depression, the number of mPFC astrocytes was reduced; however, the ability of mPFC astrocytes to repopulate after L-AAA-induced deletion was largely unaltered. Our study highlights a potentially beneficial role for repopulating astrocytes in depression and provides novel therapeutic insights into enhancing local mature astrocyte generation in depression.

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来源期刊
Glia
Glia 医学-神经科学
CiteScore
13.10
自引率
4.80%
发文量
162
审稿时长
3-8 weeks
期刊介绍: GLIA is a peer-reviewed journal, which publishes articles dealing with all aspects of glial structure and function. This includes all aspects of glial cell biology in health and disease.
期刊最新文献
All the single cells: Single-cell transcriptomics/epigenomics experimental design and analysis considerations for glial biologists. R-Ras1 and R-Ras2 regulate mature oligodendrocyte subpopulations. Astrocytic NHERF-1 Increases Seizure Susceptibility by Inhibiting Surface Expression of TREK-1. Aquaporin-4 activation facilitates glymphatic system function and hematoma clearance post-intracerebral hemorrhage. The E3 ubiquitin ligase Nedd4 fosters developmental myelination in the mouse central and peripheral nervous system.
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