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Post-transcriptional mechanisms controlling neurogenesis and direct neuronal reprogramming

Neural Regeneration research 2024年第9期19卷 1929-1939页

作者： Elsa Papadimitriou Dimitra Thomaidou department of neurobiology Hellenic Pasteur InstituteAthensGreece

Neurogenesis is a tightly regulated process in time and space both in the developing embryo and in adult neurogenic niches.A drastic change in the transcriptome and proteome of radial glial cells or neural stem cells towards the neuronal state is achieved due to sophisticated mechanisms of epigenetic,transcriptional,and post-transcriptional *** these neurogenic mechanisms is of major importance,not only for shedding light on very complex and crucial developmental processes,but also for the identification of putative reprogramming factors,that harbor hierarchically central regulatory roles in the course of neurogenesis and bare thus the capacity to drive direct reprogramming towards the neuronal *** major transcriptional programs that orchestrate the neurogenic process have been the focus of research for many years and key neurogenic transcription factors,as well as repressor complexes,have been identified and employed in direct reprogramming protocols to convert non-neuronal cells,into functional *** post-transcriptional regulation of gene expression during nervous system development has emerged as another important and intricate regulatory layer,strongly contributing to the complexity of the mechanisms controlling neurogenesis and neuronal *** particular,recent advances are highlighting the importance of specific RNA binding proteins that control major steps of mRNA life cycle during neurogenesis,such as alternative splicing,polyadenylation,stability,and *** from the RNA binding proteins,microRNAs,a class of small non-coding RNAs that block the translation of their target mRNAs,have also been shown to play crucial roles in all the stages of the neurogenic process,from neural stem/progenitor cell proliferation,neuronal differentiation and migration,to functional ***,we provide an overview of the most prominent post-transcriptional mechanisms mediated by RNA binding proteins and microRNAs during the

关键词： direct neuronal reprogramming in vivo glia-to-neuron conversion microRNAs neurogenesis post-transcriptional regulation RNA binding proteins

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Pathology of pain and its implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2851-2899页

作者： Bo Cao Qixuan Xu Yajiao Shi Ruiyang Zhao Hanghang Li Jie Zheng Fengyu Liu You Wan Bo Wei department of General Surgery First Medical CenterChinese PLA General HospitalBeijing 100853China Medical School of Chinese PLA Beijing 100853China neuroscience research institute and department of neurobiology School of Basic Medical SciencesKey Laboratory for NeuroscienceMinistry of Education/National Health CommissionPeking UniversityBeijing 100191China

Pain is estimated to affect more than 20%of the global population,imposing incalculable health and economic *** pain management is crucial for individuals suffering from ***,the current methods for pain assessment and treatment fall short of clinical *** from advances in neuroscience and biotechnology,the neuronal circuits and molecular mechanisms critically involved in pain modulation have been *** research achievements have incited progress in identifying new diagnostic and therapeutic *** this review,we first introduce fundamental knowledge about pain,setting the stage for the subsequent *** review next delves into the molecular mechanisms underlying pain disorders,including gene mutation,epigenetic modification,posttranslational modification,inflammasome,signaling pathways and *** better present a comprehensive view of pain research,two prominent issues,sexual dimorphism and pain comorbidities,are discussed in detail based on current *** status quo of pain evaluation and manipulation is summarized.A series of improved and innovative pain management strategies,such as gene therapy,monoclonal antibody,brain-computer interface and microbial intervention,are making strides towards clinical *** highlight existing limitations and future directions for enhancing the quality of preclinical and clinical *** to decipher the complexities of pain pathology will be instrumental in translating scientific discoveries into clinical practice,thereby improving pain management from bench to bedside.

关键词： pain thereby summarized

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Distributions of Visual Receptive Fields from Retinotopic to Craniotopic Coordinates in the Lateral Intraparietal Area and Frontal Eye Fields of the Macaque

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neuroscience Bulletin 2024年第2期40卷 171-181页

作者： Lin Yang Min Jin Cong Zhang Ning Qian Mingsha Zhang Key Laboratory of Cognitive neuroscience and Learning Division of PsychologyBeijing Normal UniversityBeijing 100875China institute of neuroscience Key Laboratory of Primate NeurobiologyCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China department of neuroscience and Zuckerman institute Columbia UniversityNew York 10027USA

Even though retinal images of objects change their locations following each eye movement,we perceive a stable and continuous *** possible mechanism by which the brain achieves such visual stability is to construct a craniotopic coordinate by integrating retinal and extraretinal *** have been several proposals on how this may be done,including eye-position modulation(gain fields)of retinotopic receptive fields(RFs)and craniotopic *** the present study,we investigated coordinate systems used by RFs in the lateral intraparietal(LIP)cortex and frontal eye fields(FEF)and compared the two *** mapped the two-dimensional RFs of neurons in detail under two eye fixations and analyzed how the RF of a given neuron changes with eye position to determine its coordinate *** same recording and analysis procedures were applied to the two brain *** found that,in both areas,RFs were distributed from retinotopic to craniotopic *** was no significant difference between the distributions in the LIP and *** a small fraction of neurons was fully craniotopic,whereas most neurons were between the retinotopic and craniotopic *** distributions were strongly biased toward the retinotopic side but with significant craniotopic *** results suggest that there is only weak evidence for craniotopic RFs in the LIP and FEF,and that transformation from retinotopic to craniotopic coordinates in these areas must rely on other factors such as gain fields.

关键词： Reference frames Eye-centered Headcentered Visual stability

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Cell replacement with stem cell-derived retinal ganglion cells from different protocols

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Neural Regeneration research 2024年第4期19卷 807-810页

作者： Ziming Luo Kun-Che Chang Spencer Center for Vision research Byers Eye InstituteStanford University School of Medicine department of Ophthalmology Louis J.Fox Center for Vision RestorationUniversity of Pittsburgh School of Medicine department of neurobiology Center of NeuroscienceUniversity of Pittsburgh School of Medicine

Glaucoma,characterized by a degenerative loss of retinal ganglion cells,is the second leading cause of blindness *** is currently no cure for vision loss in glaucoma because retinal ganglion cells do not regenerate and are not replaced after *** stem cell-derived retinal ganglion cell transplant is a potential therapeutic strategy for retinal ganglion cell degenerative *** this review,we first discuss a 2D protocol for retinal ganglion cell differentiation from human stem cell culture,including a rapid protocol that can generate retinal ganglion cells in less than two weeks and focus on their transplantation ***,we discuss using 3D retinal organoids for retinal ganglion cell transplantation,comparing cell suspensions and *** review provides insight into current knowledge on human stem cell-derived retinal ganglion cell differentiation and transplantation,with an impact on the field of regenerative medicine and especially retinal ganglion cell degenerative diseases such as glaucoma and other optic neuropathies.

关键词： cell clumps cell suspension cell transplantation differentiation direct-induced protocol glaucoma optic neuropathy regenerative medicine retinal ganglion cell retinal organoids stem cells

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Neuroimmune interactions and their roles in neurodegenerative diseases

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Fundamental research 2024年第2期4卷 251-261页

作者： Bai-Rong Chen Ting Wu Ting-Hui Chen Yun Wang neuroscience research institute and department of neurobiology School of Basic Medical SciencesKey Laboratory for NeuroscienceMinistry of Education/National Health Commission and State Key Laboratory of Natural and Biomimetic DrugsPeking UniversityBeijing 100083China PKU-IDG/McGovern institute for Brain research Peking UniversityBeijing 100871China

The nervous system possesses bidirectional,sophisticated and delicate communications with the immune *** neuroimmune interactions play a vitally important role in the initiation and development of many disorders,especially neurodegenerative *** scientific advancements have made tremendous progress in this field during the last few years,neuroimmune communications are still far from being *** organizing recent research,in this review,we discuss the local and intersystem neuroimmune interactions and their roles in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral *** these will help us gain a better understanding of the process of interplay inside the body and how the organism maintains *** will also facilitate a view of the diseases from a holistic,pluralistic and interconnected perspective,thus providing a basis of developing novel and effective methods to diagnose,intervene and treat diseases.

关键词： Nervous system Immune system Neuroimmune interactions Alzheimer’s disease Parkinson’s disease Amyotrophic lateral sclerosis

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The physiological role of the unfolded protein response in the nervous system

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Neural Regeneration research 2024年第11期19卷 2411-2420页

作者： Shuangchan Wu Wensheng Lin department of neuroscience University of MinnesotaMinneapolisMNUSA institute for Translational neuroscience University of MinnesotaMinneapolisMNUSA

The unfolded protein response(UPR)is a cellular stress response pathway activated when the endoplasmic reticulum,a crucial organelle for protein folding and modification,encounters an accumulation of unfolded or misfolded *** UPR aims to restore endoplasmic reticulum homeostasis by enhancing protein folding capacity,reducing protein biosynthesis,and promoting protein *** also plays a pivotal role in coordinating signaling cascades to determine cell fate and function in response to endoplasmic reticulum *** research has highlighted the significance of the UPR not only in maintaining endoplasmic reticulum homeostasis but also in influencing various physiological processes in the nervous ***,we provide an overview of recent findings that underscore the UPR’s involvement in preserving the function and viability of neuronal and myelinating cells under physiological conditions,and highlight the critical role of the UPR in brain development,memory storage,retinal cone development,myelination,and maintenance of myelin thickness.

关键词： myelin neuron oligodendrocyte Schwann cell unfolded protein response

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Migratory mode transition of astrocyte progenitors in the cerebral cortex: an intrinsic or extrinsic cell process?

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Neural Regeneration research 2024年第3期19卷 471-472页

作者： Michio Miyajima Hidenori Tabata Kazunori Nakajima department of Anatomy Keio University School of MedicineShinjuku-kuTokyoJapan department of Molecular neurobiology Institute for Developmental ResearchAichi Developmental Disability CenterKasugaiAichiJapan

The cerebral cortex is comprised of properly localized cell types that exert their specific *** the developing brain,cells migrate from the germinal region to their functional locations(Silva et al.,2019;Cossart and Garel,2022).For example,neocortical excitatory neurons are generated in the cerebral ventricular and subventricular zones,move to the developing cortical plate via radial migration,and reside in a radial array of six neuronal layers(Oishi and Nakajima,2018).On the other hand,cortical interneurons are mainly generated in ganglionic eminences,migrate tangentially across the cerebral cortex,and reach their final destinations in the cortex(Lim et al.,2018).The failure of neuronal migration leads to defects in cortical layer *** the mechanisms of neuronal distribution have been well examined,how astrocytes are diffusely distributed in the cortex is still *** are glial cells in the cerebral cortex with several functions,including metabolic support and synapse formation(Abbott et al.,2006;Bosworth and Allen,2017;Allen and Lyons,2018).For example,astrocytes establish synaptic connectivity in the developing brain while they contact numerous synapses and maintain optimal neuronal activity in the adult *** the developing brain,astrocytes are primarily generated from radial glia after the neurogenic *** a certain type of astrocyte called fibrous astrocytes populates the white matter,protoplasmic astrocytes migrate to the cortical plate during neural network formation.

关键词： cerebral migrate Abbott

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TET1 Participates in Complete Freund’s Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model

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neuroscience Bulletin 2024年第6期40卷 707-718页

作者： Dengcheng Zhan Jingjing Zhang Songxue Su Xiuhua Ren Sen Zhao Weidong Zang Jing Cao department of Human Anatomy School of Basic Medical SciencesZhengzhou UniversityZhengzhou450001China neuroscience research institute Zhengzhou UniversityZhengzhou450001China

Trigeminal inflammatory pain is one of the most severe pain-related disorders in humans;however,the underlying mechanisms remain largely *** this study,we investigated the possible contribution of interaction between ten-eleven translocation methylcytosine dioxygenase 1(TET1)and the voltage-gated K^(+)channel Kv7.2(encoded by Kcnq2)to orofacial inflammatory pain in *** found that complete Freund’s adjuvant(CFA)injection reduced the expression of Kcnq2/Kv7.2 in the trigeminal ganglion(TG)and induced orofacial inflammatory *** involvement of Kv7.2 in CFA-induced orofacial pain was further confirmed by Kv7.2 knockdown or ***,TET1 knockdown in Tet1^(flox/flox)mice significantly reduced the expression of Kv7.2 and M currents in the TG and led to pain-like ***,TET1 overexpression by lentivirus rescued the CFA-induced decreases of Kcnq2 and M currents and alleviated mechanical *** data suggest that TET1 is implicated in CFA-induced trigeminal inflammatory pain by positively regulating Kv7.2 in TG neurons.

关键词： Facial pain KCNQ2 potassium channel TET1 protein

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Beyond functional MRI signals:molecular and cellular modifiers of the functional connectome and cognition

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Neural Regeneration research 2024年第5期19卷 937-938页

作者： Lorenzo Pini Alessandro Salvalaggio Maurizio Corbetta Padova neuroscience Center University of PadovaItaly Veneto institute of Molecular Medicine VIMMPadovaItaly department of neuroscience University of PadovaItaly

Our brain is constantly *** at rest,the brain carries out essential functions such as maintenance of resting potentials,subthreshold synaptic activity,and spiking activity related to information *** resting activity can be assessed with several in vivo tools,such as resting-state functional magnetic resonance *** technique measures subtle changes in blood flow,volume,and oxygenation that occur over *** vascular in nature,resting-state functional magnetic resonance imaging is considered a reliable proxy of neural activity and several studies have shown that the brain is functionally divided into interacting neural networks called the“functional connectome”.

关键词： functional neural measures

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Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

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Neural Regeneration research 2024年第3期19卷 493-494页

作者： Melissa Schepers Tim Vanmierlo department of neuroscience Biomedical Research InstituteFaculty of Medicine and Life SciencesHasselt UniversityHasseltBelgium department of Psychiatry and Neuropsychology School for Mental Health and NeuroscienceMaastricht UniversityMaastrichtNetherlands University MS Center(UMSC)Hasselt-Pelt HasseltBelgium

In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is ***,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon *** to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in ***,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.

关键词： impaired inflammation Marie

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