Nature neuroscience最新文献_第4页

Turning back the clock on age-related neurodegeneration 逆转与年龄相关的神经退化

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-13 DOI: 10.1038/s41593-025-02036-8

引用次数: 0

Cross-species analysis of adult hippocampal neurogenesis reveals human-specific features 成人海马神经发生的跨物种分析揭示了人类特有的特征

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-12 DOI: 10.1038/s41593-025-02029-7

引用次数: 0

The brain drain puts aging myelin in deep trouble 人才流失使老化的髓磷脂陷入严重困境

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-12 DOI: 10.1038/s41593-025-02028-8

Ahlem Assali, Nicolas Renier

引用次数: 0

Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons 胚胎运动神经元编程因子重新激活未成熟基因表达并抑制出生后运动神经元的ALS病理

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-12 DOI: 10.1038/s41593-025-02033-x

Emily R. Lowry, Tulsi Patel, Jonathon A. Costa, Elizabeth Chang, Shahroz Tariq, Hranush Melikyan, Ian Davis, Siaresh Aziz, Georgia Ntermentzaki, Francesco Lotti, Hynek Wichterle

{"title":"Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons","authors":"Emily R. Lowry, Tulsi Patel, Jonathon A. Costa, Elizabeth Chang, Shahroz Tariq, Hranush Melikyan, Ian Davis, Siaresh Aziz, Georgia Ntermentzaki, Francesco Lotti, Hynek Wichterle","doi":"10.1038/s41593-025-02033-x","DOIUrl":"10.1038/s41593-025-02033-x","url":null,"abstract":"Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by reexpression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral reexpression of ISL1 and LHX3 selectively in postnatal motor neurons reactivates aspects of their youthful gene expression program and alleviates key disease-relevant phenotypes in the SOD1G93A mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease. Lowry et al. use embryonic motor neuron selector transcription factors to partially rejuvenate the gene expression profile of mature neurons, making them more resistant to an ALS model without compromising their normal function.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 10","pages":"2044-2053"},"PeriodicalIF":20.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819149","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

Impaired capillary–venous drainage contributes to gliosis and demyelination in mouse white matter during aging 在衰老过程中，毛细血管-静脉引流受损导致小鼠白质胶质增生和脱髓鞘

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-12 DOI: 10.1038/s41593-025-02023-z

Stefan Stamenkovic, Franca Schmid, Gokce Gurler, Farzaneh Abolmaali, Nicolas A. Weitermann, Kevin T. Takasaki, Stephanie K. Bonney, Maria J. Sosa, Hannah C. Bennett, Yongsoo Kim, Jack Waters, Andy Y. Shih

{"title":"Impaired capillary–venous drainage contributes to gliosis and demyelination in mouse white matter during aging","authors":"Stefan Stamenkovic, Franca Schmid, Gokce Gurler, Farzaneh Abolmaali, Nicolas A. Weitermann, Kevin T. Takasaki, Stephanie K. Bonney, Maria J. Sosa, Hannah C. Bennett, Yongsoo Kim, Jack Waters, Andy Y. Shih","doi":"10.1038/s41593-025-02023-z","DOIUrl":"10.1038/s41593-025-02023-z","url":null,"abstract":"The progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or a consequence remains debatable. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and the corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical venules, which exclusively drain deep tissues and resemble the vasculature at the human cortex and U-fiber interface. Aging led to selective constriction and rarefaction of capillaries in deep branches of principal cortical venules. This resulted in mild hypoperfusion that was associated with microgliosis, astrogliosis and demyelination in deep tissues, but not the upper cortex. Induction of comparable hypoperfusion in adult mice using carotid artery stenosis triggered a similar tissue pathology specific to layer 6 and the corpus callosum. Thus, impaired capillary–venous drainage is a contributor to hypoperfusion and a potential therapeutic target for preserving blood flow to white matter during aging. How reduced blood flow plays a role in progressive white matter loss during aging and associated cognitive decline is unclear. Here the authors show that selective constriction and rarefaction of capillary–venous networks contribute to age-related hypoperfusion and white matter damage in mice.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 9","pages":"1868-1882"},"PeriodicalIF":20.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02023-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Layer-specific changes in sensory cortex across the lifespan in mice and humans 小鼠和人类一生中感觉皮层的层特异性变化

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-11 DOI: 10.1038/s41593-025-02013-1

Peng Liu, Juliane Doehler, Julia U. Henschke, Alicia Northall, Angela Knaf-Serian, Laura C. Loaiza-Carvajal, Eike Budinger, Dietrich S. Schwarzkopf, Oliver Speck, Janelle M. P. Pakan, Esther Kuehn

{"title":"Layer-specific changes in sensory cortex across the lifespan in mice and humans","authors":"Peng Liu, Juliane Doehler, Julia U. Henschke, Alicia Northall, Angela Knaf-Serian, Laura C. Loaiza-Carvajal, Eike Budinger, Dietrich S. Schwarzkopf, Oliver Speck, Janelle M. P. Pakan, Esther Kuehn","doi":"10.1038/s41593-025-02013-1","DOIUrl":"10.1038/s41593-025-02013-1","url":null,"abstract":"The segregation of processes into cortical layers is a convergent feature in animal evolution. However, how changes in the cortical layer architecture interact with sensory system function and dysfunction remains unclear. Here we conducted functional and structural layer-specific in vivo 7T magnetic resonance imaging of the primary somatosensory cortex in two cohorts of healthy younger and older adults. Input layer IV is enlarged and more myelinated in older adults and is associated with extended sensory input signals. Age-related cortical thinning is driven by deep layers and accompanied by increased myelination, but there is no clear evidence for reduced inhibition. Calcium imaging and histology in younger and older mice revealed increased sensory-evoked neuronal activity accompanied by increased parvalbumin expression as a potential inhibitory balance, with dynamic changes in layer-specific myelination across age groups. Using multimodal imaging, we demonstrate that middle and deep layers show specific sensitivity to aging across species. The principal layer architecture of the sensory cortex is altered with aging. The authors show that overall thinning of the primary somatosensory cortex is driven by deep layer degeneration but that layer IV is more pronounced in old age.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 9","pages":"1978-1989"},"PeriodicalIF":20.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41593-025-02013-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential kinematic coding in sensorimotor striatum across behavioral domains reflects different contributions to movement 不同行为域的感觉运动纹状体的不同运动编码反映了对运动的不同贡献

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-11 DOI: 10.1038/s41593-025-02026-w

Kiah Hardcastle, Jesse D. Marshall, Amanda Gellis, Ugne Klibaite, Cheshta Bhatia, William L. Wang, Selimzhan Chalyshkan, Bence P. Ölveczky

{"title":"Differential kinematic coding in sensorimotor striatum across behavioral domains reflects different contributions to movement","authors":"Kiah Hardcastle, Jesse D. Marshall, Amanda Gellis, Ugne Klibaite, Cheshta Bhatia, William L. Wang, Selimzhan Chalyshkan, Bence P. Ölveczky","doi":"10.1038/s41593-025-02026-w","DOIUrl":"10.1038/s41593-025-02026-w","url":null,"abstract":"The sensorimotor arm of the basal ganglia is a major part of the mammalian motor control network, yet whether it supports all movements or is specialized for task-oriented behaviors remains unclear. To examine this, we probed the contributions of the rat sensorimotor striatum (dorsolateral striatum (DLS)) in two behavioral domains: free exploration, in which naturalistic behaviors are expressed, and during a motor task. In contrast to prior work, which showed the DLS being essential for generating task-specific learned movements, DLS lesions had no effect on naturalistic behaviors like rearing, grooming or walking. To explore the neural basis of this functional dissociation, we compared DLS activity across the two domains. Although neural activity reflected movement kinematics in both, the kinematic codes differed starkly. These findings suggest that sensorimotor basal ganglia are not essential parts of mammalian motor control but, rather, shift their output into a motor-potent space to shape task-specific behaviors. Hardcastle and Marshall et al. show that striatal function is domain specific, required for task-related but not spontaneously expressed movements. This functional distinction is reflected in starkly different kinematic codes across the domains.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 9","pages":"1932-1945"},"PeriodicalIF":20.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812896","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

Cross-species analysis of adult hippocampal neurogenesis reveals human-specific gene expression but convergent biological processes 成人海马神经发生的跨物种分析揭示了人类特异性基因表达，但趋同的生物学过程

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-11 DOI: 10.1038/s41593-025-02027-9

Yi Zhou, Yijing Su, Qian Yang, Jiaqi Li, Yan Hong, Taosha Gao, Yanqing Zhong, Xueting Ma, Mengmeng Jin, Xinglan Liu, Nini Yuan, Benjamin C. Kennedy, Lizhou Wang, Longying Yan, Angela N. Viaene, Ingo Helbig, Sudha K. Kessler, Joel E. Kleinman, Thomas M. Hyde, David W. Nauen, Cirong Liu, Zhen Liu, Zhiming Shen, Chao Li, Shengjin Xu, Jie He, Daniel R. Weinberger, Guo-li Ming, Hongjun Song

{"title":"Cross-species analysis of adult hippocampal neurogenesis reveals human-specific gene expression but convergent biological processes","authors":"Yi Zhou, Yijing Su, Qian Yang, Jiaqi Li, Yan Hong, Taosha Gao, Yanqing Zhong, Xueting Ma, Mengmeng Jin, Xinglan Liu, Nini Yuan, Benjamin C. Kennedy, Lizhou Wang, Longying Yan, Angela N. Viaene, Ingo Helbig, Sudha K. Kessler, Joel E. Kleinman, Thomas M. Hyde, David W. Nauen, Cirong Liu, Zhen Liu, Zhiming Shen, Chao Li, Shengjin Xu, Jie He, Daniel R. Weinberger, Guo-li Ming, Hongjun Song","doi":"10.1038/s41593-025-02027-9","DOIUrl":"10.1038/s41593-025-02027-9","url":null,"abstract":"Immature dentate granule cells (imGCs) arising from adult hippocampal neurogenesis contribute to plasticity, learning and memory, but their evolutionary changes across species and specialized features in humans remain poorly understood. Here we performed machine-learning-augmented analysis of published single-nucleus RNA-sequencing datasets and identified macaque imGCs with transcriptome-wide immature neuronal characteristics. Our cross-species comparisons among humans, monkeys, pigs and mice showed few shared (such as DPYSL5), but mostly species-specific gene expression in imGCs that converged onto common biological processes regulating neuronal development. We further identified human-specific transcriptomic features of imGCs and demonstrated the functional roles of human imGC-enriched expression of a family of proton-transporting vacuolar-type ATPase subtypes in the development of imGCs derived from human pluripotent stem cells. Our study reveals divergent gene expression patterns but convergent biological processes in the molecular characteristics of imGCs across species, highlighting the importance of conducting independent molecular and functional analyses for adult neurogenesis in different species. Machine-learning-augmented single-nucleus transcriptomic analysis compared molecular landscapes of immature neurons in the mammalian hippocampus across species, highlighting human-specific gene expression but convergent biological processes.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 9","pages":"1820-1829"},"PeriodicalIF":20.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812902","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 pancreas–hippocampus feedback mechanism regulates circadian changes in depression-related behaviors 胰腺-海马反馈机制调节抑郁相关行为的昼夜节律变化

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-11 DOI: 10.1038/s41593-025-02040-y

Yao-Nan Liu, Qiu-Wen Wang, Xin-Yu She, Li-Jun Li, Bing Wang, Ruilan Yang, Qian Li, Si-Yao Lu, Ying-Han Wang, Wei Shen, Chong-Lei Fu, Dan Li, Lan Yi, Chun-Xue Wang, Wei Shi, Xin Cheng, Liping Cao, Shuangli Mi, Jun Yao

{"title":"A pancreas–hippocampus feedback mechanism regulates circadian changes in depression-related behaviors","authors":"Yao-Nan Liu, Qiu-Wen Wang, Xin-Yu She, Li-Jun Li, Bing Wang, Ruilan Yang, Qian Li, Si-Yao Lu, Ying-Han Wang, Wei Shen, Chong-Lei Fu, Dan Li, Lan Yi, Chun-Xue Wang, Wei Shi, Xin Cheng, Liping Cao, Shuangli Mi, Jun Yao","doi":"10.1038/s41593-025-02040-y","DOIUrl":"10.1038/s41593-025-02040-y","url":null,"abstract":"Individuals with neuropsychiatric disorders often show metabolic symptoms. However, the mechanisms underlying this co-occurrence remain unclear. Here we show that induced pluripotent stem cell-derived pancreatic islets from individuals with bipolar disorder have insulin secretion deficits caused by increased expression of RORβ, a susceptibility gene for bipolar disorder. Enhancing RORβ expression in mouse pancreatic β cells induced depression-related behaviors in the light phase and mania-like behaviors in the dark phase. Pancreatic RORβ overexpression in the light phase reduced insulin release from islets, inducing hippocampal hyperactivity and depression-like behaviors. Furthermore, this hippocampal hyperactivity in the light phase had the delayed effect of promoting insulin release in the dark phase, resulting in mania-like behaviors and hippocampal neuronal hypoactivity. Our results in mice point to a pancreas–hippocampus feedback mechanism by which metabolic and circadian factors cooperate to generate behavioral fluctuations and which may play a role in bipolar disorder. The mechanisms linking neuropsychiatric and metabolic disorders remain unclear. The authors show a pancreas–hippocampus feedback loop whereby metabolic and circadian factors drive behavioral fluctuations, with potential relevance for bipolar disorder.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 10","pages":"2078-2091"},"PeriodicalIF":20.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812900","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

Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD 异常剪接导致ALS/FTD中C9orf72重复扩增

IF 2 1区医学

Nature neuroscience Pub Date : 2025-08-11 DOI: 10.1038/s41593-025-02039-5

Suzhou Yang, Denethi Wijegunawardana, Udit Sheth, Austin M. Veire, Juliana M. S. Salgado, Tanina Arab, Manasi Agrawal, Jeffrey Zhou, João D. Pereira, Tania F. Gendron, Junjie U. Guo

{"title":"Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD","authors":"Suzhou Yang, Denethi Wijegunawardana, Udit Sheth, Austin M. Veire, Juliana M. S. Salgado, Tanina Arab, Manasi Agrawal, Jeffrey Zhou, João D. Pereira, Tania F. Gendron, Junjie U. Guo","doi":"10.1038/s41593-025-02039-5","DOIUrl":"10.1038/s41593-025-02039-5","url":null,"abstract":"A nucleotide repeat expansion (NRE) (GGGGCC)n within the first annotated intron of the C9orf72 (C9) gene is a common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While previous studies have shown that C9 NRE produces several toxic dipeptide repeat (DPR) proteins, the mechanism by which an intronic RNA segment can access the cytoplasmic translation machinery remains unclear. By selectively capturing and sequencing NRE-containing RNAs (NRE-capture-seq) from patient-derived fibroblasts and neurons, we found that, in contrast to previous models, C9 NRE is retained as part of an extended exon 1 due to the usage of various downstream alternative 5′ splice sites. These aberrant splice isoforms accumulate in C9-ALS/FTD brains, and their production is promoted by serine/arginine-rich splicing factor 1 (SRSF1). Antisense oligonucleotides targeting either SRSF1 or the aberrant C9 splice isoforms reduced the levels of DPR. Together, our findings revealed a crucial role of aberrant splicing in the biogenesis of NRE-containing RNAs and demonstrated potential therapeutic strategies to target these pathogenic transcripts. By selectively isolating and sequencing the rare RNA transcripts containing C9orf72 repeat expansion from ALS–FTD neurons, the authors uncover an alternative splicing mechanism that explains the retention of this intron segment in a translated mRNA.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 10","pages":"2034-2043"},"PeriodicalIF":20.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144812899","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