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Neuroanatomical changes observed over the course of a human pregnancy 在人类怀孕期间观察到的神经解剖学变化
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-16 DOI: 10.1038/s41593-024-01741-0
Laura Pritschet, Caitlin M. Taylor, Daniela Cossio, Joshua Faskowitz, Tyler Santander, Daniel A. Handwerker, Hannah Grotzinger, Evan Layher, Elizabeth R. Chrastil, Emily G. Jacobs
Pregnancy is a period of profound hormonal and physiological changes experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation are not well studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through 2 years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, standing in contrast to increases in white matter microstructural integrity, ventricle volume and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as a comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to further explore and understand the maternal brain. Neural changes in pregnancy are not well understood. Here Pritschet et al. present an open-access precision brain imaging resource, mapping neuroanatomical change in an individual from preconception through postpartum.
每年都有数百万妇女在怀孕期间经历深刻的荷尔蒙和生理变化,但人类对整个妊娠期母体大脑神经变化的研究还不够深入。利用精确成像技术,我们绘制了一个人从怀孕前到产后两年的神经解剖变化图。整个大脑的灰质体积和皮质厚度明显减少,与之形成鲜明对比的是白质微结构完整性、脑室体积和脑脊液的增加,很少有区域在向母亲过渡时没有受到影响。该数据集是整个妊娠期人类大脑的综合地图,为大脑成像界进一步探索和了解孕产妇大脑提供了一个开放访问的资源。
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引用次数: 0
Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning 迷走神经刺激可调动中枢胆碱能系统增强知觉学习能力
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-16 DOI: 10.1038/s41593-024-01767-4
Kathleen A. Martin, Eleni S. Papadoyannis, Jennifer K. Schiavo, Saba Shokat Fadaei, Habon A. Issa, Soomin C. Song, Sofia Orrey Valencia, Nesibe Z. Temiz, Matthew J. McGinley, David A. McCormick, Robert C. Froemke
Perception can be refined by experience, up to certain limits. It is unclear whether perceptual limits are absolute or could be partially overcome via enhanced neuromodulation and/or plasticity. Recent studies suggest that peripheral nerve stimulation, specifically vagus nerve stimulation (VNS), can alter neural activity and augment experience-dependent plasticity, although little is known about central mechanisms recruited by VNS. Here we developed an auditory discrimination task for mice implanted with a VNS electrode. VNS applied during behavior gradually improved discrimination abilities beyond the level achieved by training alone. Two-photon imaging revealed VNS induced changes to auditory cortical responses and activated cortically projecting cholinergic axons. Anatomical and optogenetic experiments indicated that VNS can enhance task performance through activation of the central cholinergic system. These results highlight the importance of cholinergic modulation for the efficacy of VNS and may contribute to further refinement of VNS methodology for clinical conditions. Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.
感知可以在一定限度内通过经验得到完善。目前还不清楚知觉极限是绝对的,还是可以通过增强神经调节和/或可塑性来部分克服。最近的研究表明,外周神经刺激,特别是迷走神经刺激(VNS),可以改变神经活动并增强依赖经验的可塑性,但人们对 VNS 的中枢机制知之甚少。在此,我们为植入 VNS 电极的小鼠开发了一种听觉辨别任务。在行为过程中应用 VNS 可逐渐提高辨别能力,超过单独训练所能达到的水平。双光子成像显示,VNS诱导了听觉皮层反应的变化,并激活了皮层投射的胆碱能轴突。解剖学和光遗传学实验表明,VNS可通过激活中枢胆碱能系统提高任务表现。这些结果凸显了胆碱能调节对 VNS 疗效的重要性,可能有助于进一步完善 VNS 临床治疗方法。
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引用次数: 0
DOR activation in mature oligodendrocytes regulates α-ketoglutarate metabolism leading to enhanced remyelination in aged mice 激活成熟少突胶质细胞中的 DOR 可调节α-酮戊二酸代谢,从而增强老龄小鼠的髓鞘再形成能力
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-12 DOI: 10.1038/s41593-024-01754-9
Guojiao Huang, Zhidan Li, Xuezhao Liu, Menglong Guan, Songlin Zhou, Xiaowen Zhong, Tao Zheng, Dazhuan Xin, Xiaosong Gu, Dezhi Mu, Yingkun Guo, Lin Zhang, Liguo Zhang, Q. Richard Lu, Xuelian He
The decreased ability of mature oligodendrocytes to produce myelin negatively affects remyelination in demyelinating diseases and aging, but the underlying mechanisms are incompletely understood. In the present study, we identify a mature oligodendrocyte-enriched transcriptional coregulator diabetes- and obesity-related gene (DOR)/tumor protein p53-inducible nuclear protein 2 (TP53INP2), downregulated in demyelinated lesions of donors with multiple sclerosis and in aged oligodendrocyte-lineage cells. Dor ablation in mice of both sexes results in defective myelinogenesis and remyelination. Genomic occupancy in oligodendrocytes and transcriptome profiling of the optic nerves of wild-type and Dor conditional knockout mice reveal that DOR and SOX10 co-occupy enhancers of critical myelinogenesis-associated genes including Prr18, encoding an oligodendrocyte-enriched, proline-rich factor. We show that DOR targets regulatory elements of genes responsible for α-ketoglutarate biosynthesis in mature oligodendrocytes and is essential for α-ketoglutarate production and lipid biosynthesis. Supplementation with α-ketoglutarate restores oligodendrocyte-maturation defects in Dor-deficient adult mice and improves remyelination after lysolecithin-induced demyelination and cognitive function in 17-month-old wild-type mice. Our data suggest that activation of α-ketoglutarate metabolism in mature oligodendrocytes can promote myelin production during demyelination and aging. The mechanisms underlying the ability to remyelinate in aging and disease are unclear. Here, the authors show that DOR-mediated activation of α-ketoglutarate in mature oligodendrocytes can promote myelin production in mice during demyelination and aging.
成熟少突胶质细胞产生髓鞘的能力下降会对脱髓鞘疾病和衰老中的再髓鞘化产生负面影响,但其潜在机制尚不完全清楚。在本研究中,我们发现了一个成熟少突胶质细胞富集的转录核心调节因子糖尿病和肥胖相关基因(DOR)/肿瘤蛋白 p53 诱导核蛋白 2(TP53INP2),它在多发性硬化症供体的脱髓鞘病变和衰老的少突胶质细胞系细胞中下调。小鼠(雌雄均可)的髓鞘消融导致髓鞘生成和再髓鞘化缺陷。野生型小鼠和 Dor 条件性基因敲除小鼠视神经中的少突胶质细胞基因组占位和转录组图谱分析表明,DOR 和 SOX10 共同占据了关键的髓鞘生成相关基因的增强子,包括 Prr18(编码一种富含脯氨酸的少突胶质细胞因子)。我们的研究表明,DOR靶向成熟少突胶质细胞中负责α-酮戊二酸生物合成的基因的调控元件,并且对α-酮戊二酸的产生和脂质的生物合成至关重要。补充α-酮戊二酸可恢复Dor缺陷成年小鼠少突胶质细胞成熟缺陷,并改善溶血卵磷脂诱导脱髓鞘后的再髓鞘化和17个月大野生型小鼠的认知功能。我们的数据表明,激活成熟少突胶质细胞中的α-酮戊二酸代谢可促进脱髓鞘和衰老过程中的髓鞘生成。
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引用次数: 0
Myelin lipid metabolism can provide energy for starved axons 髓鞘脂质代谢可为饥饿的轴突提供能量
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-12 DOI: 10.1038/s41593-024-01750-z
We reveal that lipid turnover in the myelin sheath generates a fatty acid pool in oligodendrocytes that can contribute to the energy balance of white matter tracts. We also demonstrate that when glucose levels are limiting, fatty acid metabolism can support glial cell survival and the basic functional integrity of myelinated axons.
我们揭示了髓鞘中的脂质周转会在少突胶质细胞中产生一个脂肪酸池,从而有助于白质束的能量平衡。我们还证明,当葡萄糖水平受到限制时,脂肪酸代谢可以支持胶质细胞的生存和有髓鞘轴突的基本功能完整性。
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引用次数: 0
VEGF-A-mediated venous endothelial cell proliferation results in neoangiogenesis during neuroinflammation VEGF-A 介导的静脉内皮细胞增殖导致神经炎症期间的新血管生成
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-10 DOI: 10.1038/s41593-024-01746-9
Sanjid Shahriar, Saptarshi Biswas, Kaitao Zhao, Uğur Akcan, Mary Claire Tuohy, Michael D. Glendinning, Ali Kurt, Charlotte R. Wayne, Grace Prochilo, Maxwell Z. Price, Heidi Stuhlmann, Rolf A. Brekken, Vilas Menon, Dritan Agalliu
Newly formed leaky vessels and blood–brain barrier (BBB) damage are present in demyelinating acute and chronic lesions in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). However, the endothelial cell subtypes and signaling pathways contributing to these leaky neovessels are unclear. Here, using single-cell transcriptional profiling and in vivo validation studies, we show that venous endothelial cells express neoangiogenesis gene signatures and show increased proliferation resulting in enlarged veins and higher venous coverage in acute and chronic EAE lesions in female adult mice. These changes correlate with the upregulation of vascular endothelial growth factor A (VEGF-A) signaling. We also confirmed increased expression of neoangiogenic markers in acute and chronic human MS lesions. Treatment with a VEGF-A blocking antibody diminishes the neoangiogenic transcriptomic signatures and vascular proliferation in female adult mice with EAE, but it does not restore BBB function or ameliorate EAE pathology. Our data demonstrate that venous endothelial cells contribute to neoangiogenesis in demyelinating neuroinflammatory conditions. Defective neoangiogenesis and blood–brain barrier leakiness are pathological hallmarks of neuroinflammation. Here the authors show that vascular endothelial growth factor A (VEGF-A) promotes venous endothelial cell proliferation, resulting in the formation of leaky vessels around demyelinating lesions in multiple sclerosis and experimental autoimmune encephalomyelitis.
多发性硬化症(MS)和实验性自身免疫性脑脊髓炎(EAE)的脱髓鞘急慢性病变中存在新形成的渗漏血管和血脑屏障(BBB)损伤。然而,导致这些新血管渗漏的内皮细胞亚型和信号通路尚不清楚。在这里,我们利用单细胞转录谱分析和体内验证研究表明,在雌性成年小鼠的急性和慢性 EAE 病变中,静脉内皮细胞表达新血管生成基因特征,并显示出增殖增加,导致静脉扩大和静脉覆盖率升高。这些变化与血管内皮生长因子 A(VEGF-A)信号的上调有关。我们还证实了新血管生成标记物在急性和慢性人类多发性硬化病变中的表达增加。用 VEGF-A 阻断抗体治疗可减少 EAE 雌性成年小鼠的新血管生成转录组特征和血管增殖,但不能恢复 BBB 功能或改善 EAE 病理。我们的数据证明,静脉内皮细胞有助于脱髓鞘神经炎病症中的新血管生成。
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引用次数: 0
Oligodendroglial fatty acid metabolism as a central nervous system energy reserve 作为中枢神经系统能量储备的少突胶质细胞脂肪酸代谢
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-09 DOI: 10.1038/s41593-024-01749-6
Ebrahim Asadollahi, Andrea Trevisiol, Aiman S. Saab, Zoe J. Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S. Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E. Dale Abel, Andrea Ballabio, Brian Popko, Celia M. Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave
Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial peroxisomes protects axons from conduction blocks when glucose is limiting. Disruption of the glucose transporter GLUT1 expression in oligodendrocytes of adult mice perturbs myelin homeostasis in vivo and causes gradual demyelination without behavioral signs. This further suggests that the imbalance of myelin synthesis and degradation can underlie myelin thinning in aging and disease. Brain functions require a constant supply of glucose. However, the brain energy stores are unclear. Here, the authors show that oligodendroglial fatty acid metabolism can be an energy reserve for white matter axons, supporting their function.
大脑功能需要葡萄糖的持续供应。然而,除了星形胶质细胞中的糖原颗粒外,大脑没有已知的能量储备。在本研究中,我们报告了持续的少突胶质细胞脂质代谢为白质束提供了能量储备。在离体的成年雌雄小鼠视神经中,少突胶质细胞比星形胶质细胞更能在葡萄糖剥夺中存活。在低葡萄糖条件下,轴突的 ATP 水平和动作电位都依赖于脂肪酸的β-氧化。重要的是,持续的少突胶质细胞脂质降解会迅速影响白质的能量代谢。线粒体和少突胶质细胞过氧体中的脂肪酸β-氧化虽然不能支持高频尖峰脉冲,但却能在葡萄糖受限时保护轴突免受传导阻滞。成年小鼠少突胶质细胞中葡萄糖转运体 GLUT1 的表达中断会扰乱体内髓鞘的稳态,并导致逐渐脱髓鞘而无行为症状。这进一步表明,髓鞘合成和降解的失衡可能是衰老和疾病导致髓鞘变薄的原因。
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引用次数: 0
Dissociative and prioritized modeling of behaviorally relevant neural dynamics using recurrent neural networks 利用递归神经网络建立行为相关神经动态的分离和优先模型
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-06 DOI: 10.1038/s41593-024-01731-2
Omid G. Sani, Bijan Pesaran, Maryam M. Shanechi
Understanding the dynamical transformation of neural activity to behavior requires new capabilities to nonlinearly model, dissociate and prioritize behaviorally relevant neural dynamics and test hypotheses about the origin of nonlinearity. We present dissociative prioritized analysis of dynamics (DPAD), a nonlinear dynamical modeling approach that enables these capabilities with a multisection neural network architecture and training approach. Analyzing cortical spiking and local field potential activity across four movement tasks, we demonstrate five use-cases. DPAD enabled more accurate neural–behavioral prediction. It identified nonlinear dynamical transformations of local field potentials that were more behavior predictive than traditional power features. Further, DPAD achieved behavior-predictive nonlinear neural dimensionality reduction. It enabled hypothesis testing regarding nonlinearities in neural–behavioral transformation, revealing that, in our datasets, nonlinearities could largely be isolated to the mapping from latent cortical dynamics to behavior. Finally, DPAD extended across continuous, intermittently sampled and categorical behaviors. DPAD provides a powerful tool for nonlinear dynamical modeling and investigation of neural–behavioral data. The authors present DPAD, a deep learning method, for dynamical neural–behavioral modeling. It dissociates behaviorally relevant neural dynamics, better predicts neural–behavioral data and reveals insight into where their nonlinearities can be isolated.
要了解神经活动向行为的动态转化,就必须具备新的能力,对与行为相关的神经动态进行非线性建模、解离和优先排序,并测试有关非线性起源的假设。我们介绍了一种非线性动力学建模方法--动力学优先分解分析(DPAD),它通过多节神经网络架构和训练方法实现了这些功能。通过分析四种运动任务中的皮层尖峰和局部场电位活动,我们展示了五个使用案例。DPAD 能够进行更准确的神经行为预测。它能识别局部场电位的非线性动态变换,比传统的功率特征更能预测行为。此外,DPAD 还实现了行为预测性非线性神经降维。它能够对神经-行为转换中的非线性进行假设检验,揭示出在我们的数据集中,非线性在很大程度上可以被隔离到从潜在皮层动力学到行为的映射中。最后,DPAD 可以扩展到连续、间歇采样和分类行为。DPAD 为神经行为数据的非线性动力学建模和研究提供了强大的工具。
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引用次数: 0
The brain heals the heart 大脑能治愈心脏
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-05 DOI: 10.1038/s41593-024-01761-w
Leonie Welberg
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引用次数: 0
Molecular architecture of the human brain vasculature 人类脑血管的分子结构。
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-05 DOI: 10.1038/s41593-024-01759-4
Elisa Floriddia
{"title":"Molecular architecture of the human brain vasculature","authors":"Elisa Floriddia","doi":"10.1038/s41593-024-01759-4","DOIUrl":"10.1038/s41593-024-01759-4","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":21.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142140625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Reducing publication bias with Registered Reports 利用注册报告减少出版偏差。
IF 21.2 1区 医学 Q1 NEUROSCIENCES Pub Date : 2024-09-05 DOI: 10.1038/s41593-024-01762-9
Nature Neuroscience now welcomes Registered Reports — a publishing format designed to prioritize methodological rigor.
自然-神经科学》现在欢迎注册报告--一种旨在优先考虑方法严谨性的出版格式。
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引用次数: 0
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Nature neuroscience
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