Nature neuroscience最新文献

Inhibiting Ca2+ channels in Alzheimer’s disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia 抑制阿尔茨海默病模型小鼠的 Ca2+ 通道可松弛周细胞、改善脑血流并减少免疫细胞停滞和缺氧现象

IF 25 1区医学

Nature neuroscience Pub Date : 2024-09-18 DOI: 10.1038/s41593-024-01753-w

Nils Korte, Anna Barkaway, Jack Wells, Felipe Freitas, Huma Sethi, Stephen P. Andrews, John Skidmore, Beth Stevens, David Attwell

{"title":"Inhibiting Ca2+ channels in Alzheimer’s disease model mice relaxes pericytes, improves cerebral blood flow and reduces immune cell stalling and hypoxia","authors":"Nils Korte, Anna Barkaway, Jack Wells, Felipe Freitas, Huma Sethi, Stephen P. Andrews, John Skidmore, Beth Stevens, David Attwell","doi":"10.1038/s41593-024-01753-w","DOIUrl":"https://doi.org/10.1038/s41593-024-01753-w","url":null,"abstract":"Early in Alzheimer’s disease (AD), pericytes constrict capillaries, increasing their hydraulic resistance and trapping of immune cells and, thus, decreasing cerebral blood flow (CBF). Therapeutic approaches to attenuate pericyte-mediated constriction in AD are lacking. Here, using in vivo two-photon imaging with laser Doppler and speckle flowmetry and magnetic resonance imaging, we show that Ca2+ entry via L-type voltage-gated calcium channels (CaVs) controls the contractile tone of pericytes. In AD model mice, we identifed pericytes throughout the capillary bed as key drivers of an immune reactive oxygen species (ROS)-evoked and pericyte intracellular calcium concentration ([Ca2+]i)-mediated decrease in microvascular flow. Blocking CaVs with nimodipine early in disease progression improved CBF, reduced leukocyte stalling at pericyte somata and attenuated brain hypoxia. Amyloid β (Aβ)-evoked pericyte contraction in human cortical tissue was also greatly reduced by CaV block. Lowering pericyte [Ca2+]i early in AD may, thus, offer a therapeutic strategy to enhance brain energy supply and possibly cognitive function in AD.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236288","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

A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury 边界相关巨噬细胞在载脂蛋白E4神经血管功能障碍和白质损伤易感性中的细胞自主作用

IF 25 1区医学

Nature neuroscience Pub Date : 2024-09-18 DOI: 10.1038/s41593-024-01757-6

Antoine Anfray, Samantha Schaeffer, Yorito Hattori, Monica M. Santisteban, Nicole Casey, Gang Wang, Michael Strickland, Ping Zhou, David M. Holtzman, Josef Anrather, Laibaik Park, Costantino Iadecola

{"title":"A cell-autonomous role for border-associated macrophages in ApoE4 neurovascular dysfunction and susceptibility to white matter injury","authors":"Antoine Anfray, Samantha Schaeffer, Yorito Hattori, Monica M. Santisteban, Nicole Casey, Gang Wang, Michael Strickland, Ping Zhou, David M. Holtzman, Josef Anrather, Laibaik Park, Costantino Iadecola","doi":"10.1038/s41593-024-01757-6","DOIUrl":"https://doi.org/10.1038/s41593-024-01757-6","url":null,"abstract":"Apolipoprotein E4 (ApoE4), the strongest genetic risk factor for sporadic Alzheimer’s disease, is also a risk factor for microvascular pathologies leading to cognitive impairment, particularly subcortical white matter injury. These effects have been attributed to alterations in the regulation of the brain blood supply, but the cellular source of ApoE4 and the underlying mechanisms remain unclear. In mice expressing human ApoE3 or ApoE4, we report that border-associated macrophages (BAMs), myeloid cells closely apposed to neocortical microvessels, are both sources and effectors of ApoE4 mediating the neurovascular dysfunction through reactive oxygen species. ApoE4 in BAMs is solely responsible for the increased susceptibility to oligemic white matter damage in ApoE4 mice and is sufficient to enhance damage in ApoE3 mice. The data unveil a new aspect of BAM pathobiology and highlight a previously unrecognized cell-autonomous role of BAM in the neurovascular dysfunction of ApoE4 with potential therapeutic implications.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236283","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

Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults 无症状老年人的 Aβ 和 tau 病理学与皮层神经生理学和认知能力下降之间的协同关系

IF 25 1区医学

Nature neuroscience Pub Date : 2024-09-18 DOI: 10.1038/s41593-024-01763-8

Jonathan Gallego-Rudolf, Alex I. Wiesman, Alexa Pichet Binette, Sylvia Villeneuve, Sylvain Baillet

{"title":"Synergistic association of Aβ and tau pathology with cortical neurophysiology and cognitive decline in asymptomatic older adults","authors":"Jonathan Gallego-Rudolf, Alex I. Wiesman, Alexa Pichet Binette, Sylvia Villeneuve, Sylvain Baillet","doi":"10.1038/s41593-024-01763-8","DOIUrl":"https://doi.org/10.1038/s41593-024-01763-8","url":null,"abstract":"Animal and computational models of Alzheimer’s disease (AD) indicate that early amyloid-β (Aβ) deposits drive neurons into a hyperactive regime, and that subsequent tau depositions manifest an opposite, suppressive effect as behavioral deficits emerge. Here we report analogous changes in macroscopic oscillatory neurophysiology in the human brain. We used positron emission tomography and task-free magnetoencephalography to test the effects of Aβ and tau deposition on cortical neurophysiology in 104 cognitively unimpaired older adults with a family history of sporadic AD. In these asymptomatic individuals, we found that Aβ depositions colocalize with accelerated neurophysiological activity. In those also presenting medial–temporal tau pathology, linear mixed effects of Aβ and tau depositions indicate a shift toward slower neurophysiological activity, which was also linked to cognitive decline. We conclude that early Aβ and tau depositions relate synergistically to human cortical neurophysiology and subsequent cognitive decline. Our findings provide insight into the multifaceted neurophysiological mechanisms engaged in the preclinical phases of AD.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236282","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

Semi-orthogonal subspaces for value mediate a binding and generalization trade-off 价值的半正交子空间介导约束与泛化之间的权衡

IF 25 1区医学

Nature neuroscience Pub Date : 2024-09-17 DOI: 10.1038/s41593-024-01758-5

W. Jeffrey Johnston, Justin M. Fine, Seng Bum Michael Yoo, R. Becket Ebitz, Benjamin Y. Hayden

引用次数: 0

Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy 节律性和猝发样刺激可明显改变整个大脑皮层的网络活动

IF 25 1区医学

Nature neuroscience Pub Date : 2024-09-16 DOI: 10.1038/s41593-024-01755-8

Christina Grimm, Sian N. Duss, Mattia Privitera, Brandon R. Munn, Nikolaos Karalis, Stefan Frässle, Maria Wilhelm, Tommaso Patriarchi, Daniel Razansky, Nicole Wenderoth, James M. Shine, Johannes Bohacek, Valerio Zerbi

{"title":"Tonic and burst-like locus coeruleus stimulation distinctly shift network activity across the cortical hierarchy","authors":"Christina Grimm, Sian N. Duss, Mattia Privitera, Brandon R. Munn, Nikolaos Karalis, Stefan Frässle, Maria Wilhelm, Tommaso Patriarchi, Daniel Razansky, Nicole Wenderoth, James M. Shine, Johannes Bohacek, Valerio Zerbi","doi":"10.1038/s41593-024-01755-8","DOIUrl":"https://doi.org/10.1038/s41593-024-01755-8","url":null,"abstract":"Noradrenaline (NA) release from the locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, modulating multiple behavioral states. NA release is mediated by both tonic and burst-like LC activity. However, it is unknown whether the functional changes in target areas depend on these firing patterns. Using optogenetics, photometry, electrophysiology and functional magnetic resonance imaging in mice, we show that tonic and burst-like LC firing patterns elicit brain responses that hinge on their distinct NA release dynamics. During moderate tonic LC activation, NA release engages regions associated with associative processing, while burst-like stimulation biases the brain toward sensory processing. These activation patterns locally couple with increased astrocytic and inhibitory activity and change the brain’s topological configuration in line with the hierarchical organization of the cerebral cortex. Together, these findings reveal how the LC–NA system achieves a nuanced regulation of global circuit operations.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234451","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

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 25 1区医学

Nature neuroscience 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

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 25 1区医学

Nature neuroscience 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

{"title":"Vagus nerve stimulation recruits the central cholinergic system to enhance perceptual learning","authors":"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","doi":"10.1038/s41593-024-01767-4","DOIUrl":"https://doi.org/10.1038/s41593-024-01767-4","url":null,"abstract":"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.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234504","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

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 25 1区医学

Nature neuroscience 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

{"title":"DOR activation in mature oligodendrocytes regulates α-ketoglutarate metabolism leading to enhanced remyelination in aged mice","authors":"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","doi":"10.1038/s41593-024-01754-9","DOIUrl":"https://doi.org/10.1038/s41593-024-01754-9","url":null,"abstract":"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.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142170841","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

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 25 1区医学

Nature neuroscience Pub Date : 2024-09-12 DOI: 10.1038/s41593-024-01750-z

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 25 1区医学

Nature neuroscience 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

{"title":"VEGF-A-mediated venous endothelial cell proliferation results in neoangiogenesis during neuroinflammation","authors":"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","doi":"10.1038/s41593-024-01746-9","DOIUrl":"https://doi.org/10.1038/s41593-024-01746-9","url":null,"abstract":"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.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":null,"pages":null},"PeriodicalIF":25.0,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142160457","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