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Neural Regeneration research 2024年第8期19卷 1759-1767页

作者： Zihang Zhou Yalong Yan Heng Gu Ruiao Sun Zihan Liao Ke Xue Chuanxi Tang Department of neurobiology Xuzhou Key Laboratory of NeurobiologyXuzhou Medical UniversityXuzhouJiangsu ProvinceChina

Parkinson’s disease can affect not only motor functions but also cognitive abilities,leading to cognitive *** common issue in Parkinson’s disease with cognitive dysfunction is the difficulty in executive *** functions help us plan,organize,and control our actions based on our *** brain area responsible for executive functions is called the prefrontal co *** acts as the command center for the brain,especially when it comes to regulating executive *** role of the prefrontal cortex in cognitive processes is influenced by a chemical messenger called ***,little is known about how dopamine affects the cognitive functions of patients with Parkinson’s *** this article,the authors review the latest research on this *** start by looking at how the dopaminergic syste m,is alte red in Parkinson’s disease with executive ***,they explore how these changes in dopamine impact the synaptic structure,electrical activity,and connection components of the prefrontal *** authors also summarize the relationship between Parkinson’s disease and dopamine-related cognitive *** information may offer valuable insights and directions for further research and improvement in the clinical treatment of cognitive impairment in Parkinson’s disease.

关键词： dopamine dopamine receptor dopamine transporter executive dysfunction neural network neural oscillation prefrontal cortex synaptic plasticity

Fasudil-modified macrophages reduce inflammation and regulate the immune response in experimental autoimmune encephalomyelitis

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Neural Regeneration research 2024年第3期19卷 671-679页

作者： Chunyun Liu Shangde Guo Rong Liu Minfang Guo Qing Wang Zhi Chai Baoguo Xiao Cungen Ma Institute of Brain Science Shanxi Datong UniversityDatongShanxi ProvinceChina The Key research laboratory of Benefiting Qi for Acting Blood Cireulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/research Center of neurobiology Shanxi University of Chinese MedicineTaiyuanShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Multiple sclerosis is characterized by demyelination and neuronal loss caused by inflammatory cell activation and infiltration into the central nervous *** polarization plays an important role in the pathogenesis of experimental autoimmune encephalomyelitis,a traditional experimental model of multiple *** study investigated the effect of Fasudil on macrophages and examined the therapeutic potential of Fasudil-modified macrophages in experimental autoimmune *** found that Fasudil induced the conversion of macrophages from the pro-inflammatory M1 type to the anti-inflammatory M2 type,as shown by reduced expression of inducible nitric oxide synthase/nitric oxide,interleukin-12,and CD16/32 and increased expression of arginase-1,interleukin-10,CD14,and CD206,which was linked to inhibition of Rho kinase activity,decreased expression of toll-like receptors,nuclear factor-κB,and components of the mitogen-activated protein kinase signaling pathway,and generation of the pro-inflammatory cytokines tumor necrosis factor-α,interleukin-1β,and ***,Fasudil-modified macrophages effectively decreased the impact of experimental autoimmune encephalomyelitis,resulting in later onset of disease,lower symptom scores,less weight loss,and reduced demyelination compared with unmodified *** addition,Fasudil-modified macrophages decreased interleukin-17 expression on CD4^(+)T cells and CD16/32,inducible nitric oxide synthase,and interleukin-12 expression on F4/80^(+)macrophages,as well as increasing interleukin-10 expression on CD4^(+)T cells and arginase-1,CD206,and interleukin-10 expression on F4/80^(+)macrophages,which improved immune regulation and reduced *** findings suggest that Fasudil-modified macrophages may help treat experimental autoimmune encephalomyelitis by inducing M2 macrophage polarization and inhibiting the inflammatory response,thereby providing new insight into cell immunotherapy for m

关键词： anti-inflammatory experimental autoimmune encephalomyelitis Fasudil macrophage multiple sclerosis pro-inflammatory Rho kinase

Memory Trace for Fear Extinction:Fragile yet Reinforceable

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Neuroscience Bulletin 2024年第6期40卷 777-794页

作者： Ying Liu Shuai Ye Xin-Ni Li Wei-Guang Li Department of Rehabilitation Medicine State Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai200032China

Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing *** on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear *** brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain *** questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction *** this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.

关键词： Fear extinction memory Memory trace Fear relapse Medial prefrontal cortex Basolateral amygdala Ventral hippocampus Insular cortex Synaptic adaptations

Peripheral Mechanism of Cancer-Induced Bone Pain

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Neuroscience Bulletin 2024年第6期40卷 815-830页

作者： Yachen Yang Wei Yang Ruofan Zhang Yanqing Wang Department of Integrative Medicine and neurobiology School of Basic Medical SciencesShanghai Medical CollegeInstitute of Acupuncture ResearchInstitutes of Integrative MedicineFudan UniversityShanghai200032China Shanghai Key laboratory of Acupuncture Mechanism and Acupoint Function Shanghai Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain ScienceInstitutes of Brain ScienceFudan UniversityShanghai200032China Zhongshan-Fudan Joint Innovation Center Zhongshan528437China

Cancer-induced bone pain(CIBP)is a type of ongoing or breakthrough pain caused by a primary bone tumor or bone *** constitutes a specific pain state with distinct characteristics;however,it shares similarities with inflammatory and neuropathic *** present,although various therapies have been developed for this condition,complete relief from CIBP in patients with cancer is yet to be ***,it is urgent to study the mechanism underlying CIBP to develop efficient analgesic ***,we focused on the peripheral mechanism associated with the initiation of CIBP,which involves tissue injury in the bone and changes in the tumor microenvironment(TME)and dorsal root *** nerve–cancer and cancer–immunocyte cross-talk in the TME creates circumstances that promote tumor growth and metastasis,ultimately leading to *** peripheral mechanism of CIBP and current treatments as well as potential therapeutic targets are discussed in this review.

关键词： Cancer-induced bone pain Peripheral mechanism Tumor microenvironment Sensory nerve Immunocytes

Brain circuits for retching-like behavior

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National Science Review 2024年第1期11卷 145-160页

作者： Lifang Huo Zhimin Ye Meiling Liu Ziqing He Meizhu Huang Dapeng Li Qian Wu Qian Wang Xiaoqun Wang Peng Cao Ji Dong Congping Shang School of Basic Medical Sciences Guangzhou National Laboratory The Fifth Afflliated Hospital Guangzhou Medical University Bioland laboratory (Guangzhou Regenerative Medicine and Health Guangdong laboratory) Department of neurobiology School of Basic Medical Sciences Beijing Key Laboratory of Neural Regeneration and Repair Advanced Innovation Center for Human Brain Protection Capital Medical University State Key laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain Research Beijing Normal University Changping Life Science laboratory National Institute of Biological Sciences

Nausea and vomiting are important defensive responses to cope with pathogens and toxins that invade the body. The nucleus of the solitary tract(NTS) is important for initiating these responses. However, the molecular heterogeneities and cellular diversities of the NTS occlude a better understanding of these defensive responses. Here, we constructed the single-nucleus transcriptomic atlas of NTS cells and found multiple populations of NTS neurons that may be involved in these defensive responses. Among these, we identified Calbindin1-positive(Calb1+) NTS neurons that are molecularly distinct from Tac1+*** Calb1+neurons are critical for nausea and retching induced by cereulide; an emetic toxin secreted by Bacillus Cereus. Strikingly, we found that cereulide can directly modulate vagal sensory neurons that innervate Calb1+NTS neurons, a novel mechanism distinct from that for nausea and retching induced by Staphylococcal enterotoxin A. Together, our transcriptomic atlas of NTS neurons and the functional analyses revealed the neural mechanism for cereulide-induced retching-like behavior. These results demonstrate the molecular and cellular complexities in the brain that underlie defensive responses to the diversities of pathogens and toxins.

关键词： vomiting nausea nucleus of the solitary tract Calbindin1 neural circuits

Effects of acupuncture on hypothalamic–pituitary–adrenal axis:Current status and future perspectives

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Journal of Integrative Medicine 2024年第4期22卷 445-458页

作者： Jia-yuan Zheng Jing Zhu Yu Wang Zhan-zhuang Tian Department of Integrative Medicine and neurobiology School of Basic Medical SciencesState Key Laboratory of Medical Neurobiology and Ministry of Education Frontiers Center for Brain ScienceInstitutes of Brain ScienceInstitute of Acupuncture ResearchAcademy of Integrative MedicineShanghai Key Laboratory for Acupuncture Mechanism and Acupoint FunctionShanghai Medical CollegeFudan UniversityShanghai 200032China Department of Human Anatomy School of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghai 201203China

The hypothalamic–pituitary–adrenal(HPA) axis is a critical component of the neuroendocrine system,playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus,hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA *** review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture.

关键词： Acupuncture Electroacupuncture Hypothalamic-pituitary-adrenal axis Mechanism Neurotransmitter microRNA

Myosin Va‑dependent Transport of NMDA Receptors in Hippocampal Neurons

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Neuroscience Bulletin 2024年第8期40卷 1053-1075页

作者： Ru Gong Linwei Qin Linlin Chen Ning Wang Yifei Bao Wei Lu Ministry of Education(MOE)Key laboratory of Developmental Genes and Human Disease School of Life Science and TechnologySoutheast UniversityNanjing 210096China Department of Neurosurgery State Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceHuashan HospitalInstitute for Translational Brain ResearchFudan UniversityShanghai 200032China Department of neurobiology Nanjing Medical UniversityNanjing 210096China Co‑innovation Center of Neuroregeneration Nantong UniversityNantong 226001China

N-methyl-D-aspartate receptor(NMDAR)trafficking is a key process in the regulation of synaptic efficacy and brain ***,the molecular mechanism underlying the surface transport of NMDARs is largely *** we identified myosin Va(MyoVa)as the specific motor protein that traffics NMDARs in hippocampal *** found that MyoVa associates with NMDARs through its cargo binding *** association was increased during NMDAR surface *** of MyoVa suppressed NMDAR *** further demonstrated that Ca^(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)regulates NMDAR transport through its direct interaction with ***,MyoVa employed Rab11 family-interacting protein 3(Rab11/FIP3)as the adaptor proteins to couple themselves with NMDARs during their ***,the knockdown of FIP3 impairs hippocampal ***,we conclude that in hippocampal neurons,MyoVa conducts active transport of NMDARs in a CaMKII-dependent manner.

关键词： Myosin Va NMDA receptor CaMKⅡ Transport Memory

Pathological and therapeutic effects of extracellular vesicles in neurological and neurodegenerative diseases

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Neural Regeneration research 2024年第1期19卷 55-61页

作者： Paula lzquierdo-Altarejos Victoria Moreno-Manzano Vicente Felipo laboratory of neurobiology Centro Investigación Príncipe FelipeValenciaSpain Neuronal and Tissue Regeneration laboratory Centro Investigación Príncipe FelipeValenciaSpain

Extracellular vesicles are released by all cell types and contain proteins,microRNAs,mRNAs,and other bioactive *** vesicles play an important role in intercellular communication and in the modulation of the immune system and *** cargo of extra cellular vesicles(e.g.,proteins and microRNAs)is altered in pathological *** vesicles contribute to the pathogenesis of many pathologies associated with sustained inflammation and neuroinflammation,including cance r,diabetes,hype rammonemia and hepatic encephalopathy,and other neurological and neurodegenerative *** vesicles may cross the blood-brain barrier and transfer pathological signals from the periphery to the *** contributes to inducing neuroinflammation and cognitive and motor impairment in hyperammonemia and hepatic encephalopathy and in neurodegenerative *** mechanisms involved are beginning to be unde *** example,increased tumor necrosis factor a in extracellular vesicles from plasma of hype rammonemic rats induces neuroinflammation and motor impairment when injected into normal *** the mechanisms by which extracellular vesicles contribute to the pathogenesis of these diseases will help to develop new treatments and diagnostic tools for their easy and early *** contrast,extra cellular vesicles from mesenchymal stem cells have therapeutic utility in many of the above pathologies,by reducing inflammation and neuroinflammation and improving cognitive and motor *** extra cellular vesicles recapitulate the beneficial effects of mesenchymal stem cells and have advantages as therapeutic tools:they are less immunoge nic,may not diffe rentiate to malignant cells,cross the blood-brain barrier,and may reach more easily target *** vesicles from mesenchymal stem cells have beneficial effects in models of ischemic brain injury,Alzheimer's and Parkinson's diseases,hyperammonemia,and

关键词： extracellular vesicles inflammation cognitive function mesenchymal stem cells neurodegenerative diseases neuroinflammation therapy transforming growth factor-β

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis laboratory of Developmental Biology Department of BiologyUniversity of PatrasPatrasGreece laboratory of Cellular and Molecular neurobiology-Stem Cells Hellenic Pasteur InstituteAthensGreece Department of Physiology School of MedicineUniversity of PatrasPatrasGreece

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal ***,we extended our investigation in two clinically-relevant ***,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian ***,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of *** found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian *** agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver ***,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin *** results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by ***,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells(iPSCs) neurotrophic factors Parkinson's disease substantia

Dopamine Switches Affective States Under Acute Sleep Deprivation

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Neuroscience Bulletin 2024年第8期40卷 1205-1208页

作者： Zhou-Cai Luo Tian-Ming Gao State Key laboratory of Organ Failure research Key Laboratory of Mental Health of the Ministry of EducationGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangdong-Hong Kong Joint Laboratory for Psychiatric DisordersGuangdong Province Key Laboratory of Psychiatric DisordersGuangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi DiseasesDepartment of NeurobiologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China

The transition of affective states manifests affective regulation,wherein individuals adaptively adjust their emotional states to cope with changes in the external environment,reflecting their sensitivity and adaptability to environmental *** process of affective state transition is complex,involving both instantaneous and persistent changes influenced by environmental,behavioral,and pharmacological *** underlying neural mechanisms encompass alterations in neurotransmitter release,neural circuit activity,and the plasticity of brain structures[1].

关键词： alterations Dopamine neural