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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina state key laboratory of medical neurobiology and MOE Frontiers Center for brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1147-1164页

作者： Yan Guo Pan Xiang Xiaojiao Sun Wei Liu Jiafeng Zhou Bin Yin Lin Hou Boqin Qiang Huiliang Li Pengcheng Shu Xiaozhong Peng Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina state key laboratory of Common Mechanism Research for Major Diseases Beijing 100005China Wolfson institute for Biomedical Research University College LondonGower StreetLondon WC1E 6BTUK Chinese institute for brain Research Beijing 102206China state key laboratory of Respiratory Health and Multimorbidity Beijing 100005China institute of laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream ***,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and ***,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal ***,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and ***6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and *** finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

关键词： impaired restrain peripheral

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MAL2 DNA methylation serves as a biomarker for the diagnosis and prognosis of glioma

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Genes & Diseases 2024年第5期11卷 36-39页

作者： Hao Luo Xing Xiao Weiliang Hou Jing Cai Ming Chen Qisheng Tang Yusheng Tong Zengxin Qi Kaicheng Li Liang Chen Department of Neurosurgery Huashan HospitalShanghai Medical CollegeState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain Science and Institutes of Brain ScienceFudan UniversityShanghai 200040China National Center for Neurological Disorders Shanghai 200040China Shanghai key laboratory of brain Function and Restoration and Neural Regeneration Shanghai 200040China Tianqiao and Chrissy Chen institute Clinical Translational Research Center Shanghai 200040China Shanghai QuietD Biotechnology Co. Ltd.Shanghai 201210China

Glioma is a common and malignant brain tumor,and molecular diagnostics for glioma have received increasing attention.1,2 Previous studies have suggested that the MAL2 gene may be involved in the transcytosis of various cancers.3 This study aimed to investigate the potential of MAL2 as a biomarker for *** candidate MAL2 CpG sites were validated by pyrosequencing and used to construct a diagnostic model for *** analysis was also conducted to determine the relationship between highly methylated MAL2-specific CpG sites and the prognosis of *** findings also showed that MAL2 was more highly methylated in glioma than in other *** constructed diagnostic model can distinguish glioma from other cancers with high sensitivity(93.3%)and specificity(86.5%).Additionally,a risk score model was built based on MAL2 methylation to assess the prognosis of glioma。

关键词： glioma diagnosis MAL

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Timp1 Deletion Induces Anxiety-like Behavior in Mice

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Neuroscience Bulletin 2024年第6期40卷 732-742页

作者： Xiaotong Wang Wei Zheng Ziyi Zhu Biyu Xing Weijie Yan Ke Zhu Lingli Xiao Chaojuan Yang Mengping Wei Lei Yang Zi-Bing Jin Xueyun Bi Chen Zhang state key laboratory of Neurology and Oncology Drug Development Nanjing210000China School of Basic medical sciences Wenzhou Medical UniversityWenzhou325035China School of Basic medical sciences Beijing Key Laboratory of Neural Regeneration and RepairAdvanced Innovation Center for Human Brain ProtectionBeijing Laboratory of Oral HealthCapital Medical UniversityBeijing100069China Beijing institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing100005China Chinese institute for brain Research Beijing102206China key laboratory for Biomechanics and Mechanobiology of the Ministry of Education Beijing Advanced Innovation Center for Biomedical EngineeringSchool of Engineering MedicineBeihang UniversityBeijing100191China

The hippocampus is essential for learning and memory,but it also plays an important role in regulating emotional behavior,as hippocampal excitability and plasticity affect anxiety and *** synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1(TIMP1),a known protein inhibitor of extracellular matrix(ECM),and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various ***,the involvement of Timp1 in fear learning,anxiety,and hippocampal synaptic function remains to be *** study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear *** results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region,but the basic synaptic transmission and plasticity were normal in the Schaffer collateral *** together,our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors,but that Timp1 is not crucial for fear learning.

关键词： Timp1 Anxiety Fear Synaptic transmission Synaptic plasticity

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Longitudinal associations of cardiovascular health and vascular events with incident dementia

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Stroke & Vascular Neurology 2024年第4期9卷 418-428,I0066-I0130页

作者： Ya-Nan Ou Kevin Kuo Liu Yang Ya-Ru Zhang Shu-Yi Huang Shi-Dong Chen Yue-Ting Deng Yu Guo Rui-Qi Zhang Bang-Sheng Wu Lan Tan Qiang Dong Jian-Feng Feng Wei Cheng Jin-Tai Yu Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdaoShandongPeople's Republic of China Department of Neurology and National Center for Neurological Disorders Huashan HospitalState Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiPeople's Republic of China institute of Science and Technology for brain-inspired Intelligence Fudan UniversityShanghaiPeople's Republic of China key laboratory of Computational Neuroscience and brain-Inspired Intelligence Fudan UniversityMinistry of EducationShanghaiPeople's Republic of China

Introduction Evidence supporting cardiovascular diseases could increase the risk of dementia remains fragmented.A comprehensive study to illuminate the distinctive associations across different dementia types is still *** study is sought to:(1)determine the clinical validity of Framingham General Cardiovascular Risk Score(FGCRS)for dementia assessment and(2)examine the associations between cardiovascular diseases and the risk of *** A total of 432079 dementia-free individuals at baseline from UK Biobank were *** Cox proportional hazard models were used to investigate the prospective associations for FGCRS and a series of cardiovascular diseases with all-cause dementia(ACD)and its major components,Alzheimer’s disease(AD)and vascular dementia(VaD).Results During a median follow-up of 110.1 months,4711 individuals were diagnosed with *** was associated with increased risks across the dementia *** stratification analysis,high-risk groups have demonstrated the greatest dementia burdens,particularly to *** 74 traits,9 adverse associations,such as chronic ischaemic heart disease(ACD:HR=1.354;AD:HR=1.269;VaD:HR=1.768),atrioventricular block(ACD:HR=1.562;AD:HR=1.556;VaD:HR=2.069),heart failure(ACD:HR=1.639;AD:HR=1.543;VaD:HR=2.141)and hypotension(ACD:HR=2.912;AD:HR=2.361;VaD:HR=3.315)were *** distinctions were also found,with atrial fibrillation,cerebral infarction,and haemorrhage only associated with greater risks of ACD and *** By identifying distinctive associations between cardiovascular diseases and dementia,this study has established a comprehensive‘mapping’that may untangle the long-standing *** has demonstrated its predictivity beyond cardiovascular diseases burdens,suggesting potential opportunities for implantation.

关键词： cardiovascular diseases supporting

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Functional dissection of parabrachial substrates in processing nociceptive information

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Zoological Research 2024年第3期45卷 633-647页

作者： Jin Ke Wei-Cheng Lu Hai-Yang Jing Shen Qian Sun-Wook Moon Guang-Fu Cui Wei-Xin Qian Xiao-Jing Che Qian Zhang Shi-Shi Lai Ling Zhang Ying-Jie Zhu Jing-Dun Xie Tian-Wen Huang Shenzhen key laboratory of Drug Addiction Shenzhen-Hong Kong Institute of Brain ScienceBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China CAS key laboratory of brain Connectome and Manipulation Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of sciences Beijing 100049China Department of Anesthesiology State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China University of Science and Technology of China HefeiAnhui 230027China Department of Anesthesiology Shenzhen University General Hospital and Shenzhen University Academy of Clinical Medical SciencesShenzhen UniversityShenzhenGuangdong 518055China School of Medicine Yunnan UniversityKunmingYunnan 650091China

Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of *** lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity ***,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain *** this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such ***,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external ***,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive *** results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.

关键词： Lateral parabrachial nucleus Substance P receptor Pain affect Defensive reaction Somatosensory

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A comparison of statistical learning of naturalistic textures between DCNNs and the human visual hierarchy

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Science China(Technological sciences) 2024年第8期67卷 2310-2318页

作者： LU XinCheng YUAN ZiQi ZHANG YiChi AI HaiLin CHENG SiYuan GE YiRan FANG Fang CHEN NiHong Department of Psychological and Cognitive sciences Tsinghua UniversityBeijing 100084China IDG/McGovern institute for brain Research Tsinghua UniversityBeijing 100084China Department of Computer Science and Technology Tsinghua UniversityBeijing 100084China School of Psychological and Cognitive sciences and Beijing key laboratory of Behavior and Mental Health Peking UniversityBeijing 100871China key laboratory of Machine Perception(Ministry of Education) Peking UniversityBeijing 100871China Peking-Tsinghua Center for Life sciences Peking UniversityBeijing 100871China IDG/McGovern institute for brain Research Peking UniversityBeijing 100871China state key laboratory of brain and Cognitive Science Institute of PsychologyChinese Academy of SciencesBeijing 100101China

The visual system continuously adapts to the statistical properties of the environment. Existing evidence shows a close resemblance between deep convolutional neural networks(CNNs) and primate visual stream in neural selectivity to naturalistic textures above the primary visual processing stage. This study delves into the mechanisms of perceptual learning in CNNs,focusing on how they assimilate the high-order statistics of natural textures. Our results show that a CNN model achieves a similar performance improvement as humans, as manifested in the learning pattern across different types of high-order image statistics. While L2 was the first stage exhibiting texture selectivity, we found that stages beyond L2 were critically involved in learning. The significant contribution of L4 to learning was manifested both in the modulations of texture-selective responses and in the consequences of training with frozen connection weights. Our findings highlight learning-dependent plasticity in the mid-to-high-level areas of the visual hierarchy. This research introduces an AI-inspired approach for studying learning-induced cortical plasticity, utilizing DCNNs as an experimental framework to formulate testable predictions for empirical brain studies.

关键词： CNN perceptual learning naturalistic texture psychophysics

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Structures and ion transport mechanisms of plant high-affinity potassium transporters

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Molecular Plant 2024年第3期17卷 409-422页

作者： Jiangqin Wang Yanping Luo Fan Ye Zhong Jie Ding Shao Jian Zheng Shuai Qiao Yong Wang Jiangtao Guo Wei Yang Nannan Su international institutes of Medicine the Fourth Affiliated HospitalZhejang University School of MedicineYiwuZhejiang 322000China Department of Biophysics and Department of Neurology of the Fourth Affiliated Hospital Zhejiang University School of MedicineHangzhouZhejang 310058China state key laboratory of Plant Environmental Resilience College of Life SciencesZhejang UniversityHangzhouZhejang 310058China College of Life sciences Zhejiang UniversityHangzhouZhejiang 310058China NHC and CAMS key laboratory of medical neurobiology MOE Frontier Science Center for Brain Science and Brain-machine IntegrationSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhouZhejiang 310058China Nanhu brain-computer Interface institute Hangzhou.Zheiang 311100.China

Plant high-affinity K^(+) transporters(HKTs)mediate Na^(+) and K^(+) uptake,maintain Na^(+)/K^(+) homeostasis,and therefore play crucial roles in plant salt *** this study,we present cryoelectron microscopy structures of HKTs from two classes,classI HKT1;1 from Arabidopsis thaliana(AtHKT1;1)and class II HKT2;1 from Triticum aestivum(TaHKT2;1),in both Na^(+) -and K^(+) -bound states at 2.6-to 3.0-A ***1;1and TaHKT2;1function *** HKT subunit consists of four tan-dem domain units(D1-D4)with a repeated K^(+) -channel-like M-P-M *** each subunit,D1-D4 assemble into an ion conduction pore with a pseudo-four-fold *** both TaHKT2;1and AtHKT1;1 have only one putative Na^(+) ion bound in the selectivity filter with a similar coordination pattern,the two HKTs display different K^(+) binding modes in the ***2;1 has three K^(+) ions bound in the selec-tivity filter,but AtHKT1;1 has only two K^(+) ions bound in the filter,which has a narrowed external entrance due to the presence of a Ser residue in the first filter *** structures,along with compu-tational,mutational,and electrophysiological analyses,enable us to pinpoint key residues that are critical for the ion selectivity of *** findings provide new insights into the ion selectivity and ion transport mechanisms of plant HKTs and improve our understanding about how HKTs mediate plant salt tolerance and enhance crop growth.

关键词： HKTs structure ion selectivity mechanism salt tolerance

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Paracrine function amplifies pro-tumor electrochemical signal within neuron-glioma synapses

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Science China(Life sciences) 2024年第6期67卷 1318-1320页

作者： Yan Hu Peishan Hu Xiaozhong Peng key laboratory of Birth Defects and Related Diseases of Women and Children of MOE State Key Laboratory of BiotherapyWest China Second University HospitalSichuan UniversityChengdu 610041China Guangdong institute of Gastroenterology Department of General SurgeryGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor DiseasesThe Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100730China state key laboratory of Respiratory Health and Multimorbidity Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100730China institute of laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Neuronal activity plays a pivotal role in various physiological processes,including tissue development,homeostasis,and *** in recent years have improved our understanding of neuronal activity in brain cancers,such as glioblastoma(GBM)and diffuse midline gliomas(DMG),which are among the most prevalent and lethal cancers affecting children and ***,the neurons regulate brain cancers via two routes.

关键词： glioma homeostasis function

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DNA bridging of FOXP3 ladder-like multimer: Unveiling a novel transcriptional regulation paradigm

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The Innovation 2024年第3期5卷 15-16页

作者： Ying Lu Lanfang Li Hanting Yang Bin Li Zuoyun Wang key laboratory of Metabolism and Molecular Medicine of the Ministry of Education Shanghai Xuhui Central Hospital and School of Basic Medical SciencesFudan UniversityShanghai 200032China institute for Translational brain Research State Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceDepartment of NeurologyZhongshan HospitalFudan UniversityShanghai 200032China Center for Immune-Related Diseases at Shanghai institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China

In the latest issue of Nature,Zhang et *** a novel ladder-like structure of FOXP3-DNA interaction involving FOXP3 multimerization and remote DNA bridging through a combination of biochemistry,structural biology,cell biology,and bioinformatics analyses.1 In this commentary,we highlight their key findings and provide our insights into the research paradigm for further exploration of a novel transcriptional regulation mode as well as a therapeutic strategy from the structural aspects of the FOXP3 complex(Figure 1).

关键词： FOXP3 bridging

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