早期资源匮乏导致成年大鼠皮质星形胶质细胞增大和眶额叶皮质转录组的性别特异性变化

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Claire Deckers , Reza Karbalaei , Nylah A. Miles , Eden V. Harder , Emily Witt , Erin P. Harris , Kathryn Reissner , Mathieu E. Wimmer , Debra A. Bangasser
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引用次数: 0

摘要

星形胶质细胞的形态会影响其功能,包括对谷氨酸能信号传导的调控。这种形态会随着环境的变化而发生动态变化。然而,对生命早期的操作如何改变成年皮质星形胶质细胞形态的研究还很欠缺。我们的实验室利用大鼠出生后短暂的资源匮乏,即有限的垫料和筑巢(LBN)操作。我们之前发现,LBN 可促进成年后对成瘾相关行为的恢复能力,减少冲动、风险决策和吗啡自我给药。这些行为依赖于内侧眶额叶(mOFC)和内侧前额叶(mPFC)皮层的谷氨酸能传导。在这里,我们使用一种新颖的病毒方法测试了 LBN 是否会改变成年大鼠 mOFC 和 mPFC 中星形胶质细胞的形态。与对照组大鼠相比,事先暴露于 LBN 会导致成年雄性大鼠和雌性大鼠 mOFC 和 mPFC 中星形胶质细胞的表面积和体积增加。接下来,我们使用 OFC 组织的大量 RNA 测序来评估 LBN 大鼠中可能增加星形胶质细胞体积的转录变化。LBN 主要导致了不同表达基因的性别特异性变化。通路分析表明,LBN 会改变雄性和雌性 OFC 谷氨酸能信号传导,但该通路的基因变化在不同性别间存在差异。这可能代表了一种趋同的性别差异,即影响星形胶质细胞形态的谷氨酸能信号通过性别特异性机制被 LBN 改变。总之,这些研究强调星形胶质细胞可能是介导早期资源匮乏对成年大脑功能影响的重要细胞类型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early resource scarcity causes cortical astrocyte enlargement and sex-specific changes in the orbitofrontal cortex transcriptome in adult rats

Astrocyte morphology affects function, including the regulation of glutamatergic signaling. This morphology changes dynamically in response to the environment. However, how early life manipulations alter adult cortical astrocyte morphology is underexplored. Our lab uses brief postnatal resource scarcity, the limited bedding and nesting (LBN) manipulation, in rats. We previously found that LBN augments maternal behaviors and promotes later resilience to adult addiction-related behaviors, reducing impulsivity, risky decision-making, and morphine self-administration. These behaviors rely on glutamatergic transmission in the medial orbitofrontal (mOFC) and medial prefrontal (mPFC) cortex. Here we tested whether LBN changed astrocyte morphology in the mOFC and mPFC of adult rats using a novel viral approach that, unlike traditional markers, fully labels astrocytes. Prior exposure to LBN causes an increase in the surface area and volume of astrocytes in the mOFC and mPFC of adult males and females relative to control-raised rats. We next used bulk RNA sequencing of OFC tissue to assess transcriptional changes that could increase astrocyte size in LBN rats. LBN caused mainly sex-specific changes in differentially expressed genes. Pathway analysis revealed that OFC glutamatergic signaling is altered by LBN in males and females, but the gene changes in that pathway differed across sex. This may represent a convergent sex difference where glutamatergic signaling, which affects astrocyte morphology, is altered by LBN via sex-specific mechanisms. Collectively, these studies highlight that astrocytes may be an important cell type that mediates the effect of early resource scarcity on adult brain function.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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