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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

Advanced nano-based strategies for mRNA tumor vaccine

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Acta Pharmaceutica Sinica B 2024年第1期14卷 170-189页

作者： Yangqi Qu Jingjing Xu Tong Zhang Qinjun Chen Tao Sun Chen Jiang Key laboratory of Smart Drug Delivery(Ministry of Education) Minhang HospitalState Key Laboratory of Medical NeurobiologyDepartment of PharmaceuticsSchool of PharmacyFudan UniversityShanghai 201203China

Tumor vaccine is a promising strategy for cancer immunotherapy by introducing tumor antigens into the body to activate specific anti-tumor immune *** with the technological breakthroughs in genetic engineering and delivery systems,messenger ribonucleic acid(mRNA)technology has achieved unprecedented development and application over the last few years,especially the emergency use authorizations of two mRNA vaccines during the COVID-19 pandemic,which has saved countless lives and makes the world witness the powerful efficacy of mRNA technology in ***,unlike infectious disease vaccines,which mainly induce humoral immunity,tumor vaccines also need to activate potent cellular immunity to control tumor growth,which creates a higher demand for mRNA delivery to the lymphatic organs and antigen-presenting cells(APCs).Here we review the existing bottlenecks of mRNA tumor vaccines and advanced nano-based strategies to overcome those challenges,as well as future considerations of mRNA tumor vaccines and their delivery systems.

关键词： mRNA vaccine Nanoparticle Tumor vaccine Delivery system Stability Targeting Transfection Immunogenicity

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

BMP7 expression in mammalian cortical radial glial cells increases the length of the neurogenic period

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Protein & Cell 2024年第1期15卷 21-35页

作者： Zhenmeiyu Li Guoping Liu Lin Yang Mengge Sun Zhuangzhi Zhang Zhejun Xu Yanjing Gao Xin Jiang Zihao Su Xiaosu Li Zhengang Yang State Key laboratory of Medical neurobiology and MOE Frontiers Center for Brain Science Institutes of Brain Scienceand Department of NeurologyZhongshan HospitalFudan UniversityShanghai 200433China

The seat of human intelligence is the human cerebral cortex,which is responsible for our exceptional cognitive *** principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so *** remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells,primary neural stem cells in the cortex,generate cortical pyramidal neurons for more than 130 days,whereas the same process takes only about 7 days in *** molecular mechanisms underlying this difference are largely ***,we found that bone morphogenic protein 7(BMP7)is expressed by increasing the number of corti-cal radial glial cells during mammalian evolution(mouse,ferret,monkey,and human).BMP7 expression in cortical radial glial cells promotes neurogenesis,inhibits gliogenesis,and thereby increases the length of the neurogenic period,whereas Sonic Hedgehog(SHH)signaling promotes cortical *** demonstrate that BMP7 sign-aling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor *** propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.

关键词： radial glia cortical neurogenesis cortical gliogenesis cortical evolution BMP7 SHH

Neural Circuitry Involving Substance P in Male Sexual Behavior

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Neuroscience Bulletin 2024年第4期40卷 544-546页

作者： Xinrong Wang Junqiang Zheng Han Xu Department of neurobiology and Department of Neurology of the Second Affiliated Hospital and School of Brain Science and Brain Medicine Zhejiang University School of MedicineHangzhou310058China Nanhu Brain-Computer Interface Institute Hangzhou311100China Liangzhu laboratory MOE Frontier Science Center for Brain Science and Brain-machine IntegrationState Key Laboratory of Brain-Machine IntelligenceZhejiang UniversityHangzhou311121China NHC and CAMS Key laboratory of Medical neurobiology Zhejiang UniversityHangzhou310058China Lingang laboratory Shanghai200031China

Male sexual behavior is an innate social behavior crucial for reproduction[1].Previous studies have identified several brain regions crucial for the control of both sexual and aggressive behaviors in ***,molecularly specified neural circuits that specifically control male sexual behavior remain *** with the inherently rewarding nature of sexual behavior,previous research has implicated the role of the dopamine system in regulating sexual desire[2].However,the interaction between reward and copulation at the circuit level remains largely ***,it is unclear if the associated neural pathways are specific in modulating sexual reward.

关键词： behavior neural specified

Application of total keratometry in ten intraocular lens power calculation formulas in highly myopic eyes

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Eye and Vision 2024年第2期10卷 22-30页

作者： Ling Wei Kaiwen Cheng Wenwen He Xiangjia Zhu Yi Lu Department of Ophthalmology and Eye Institute Eye and ENT Hospital of Fudan UniversityShanghai 200031China Key laboratory of Myopia(Fudan University)Key laboratory of MyopiaShanghai Key laboratory of Visual Impairment and Restoration National Health CommissionChinese Academy of Medical ScienceShanghai 200031China State Key laboratory of Medical neurobiology Fudan UniversityShanghai 200031China

Background:The accuracy of using total keratometry(TK)value in recent IOL power calculation formulas in highly myopic eyes remained ***:Highly myopic patients who underwent uneventful cataract surgery were prospectively enrolled in this prospective comparative *** one month postoperatively,standard deviation(SD)of the prediction errors(PEs),mean and median absolute error(MedAE)of 103 highly myopic eyes were back-calculated and compared among ten formulas,including XGboost,RBF 3.0,Kane,Barrett Universal II,Emmetropia Verifying Optical 2.0,Cooke K6,Haigis,SRK/T,and Wang-Koch modifications of Haigis and SRK/T formulas,using either TK or standard keratometry(K)***:In highly myopic eyes,despite good agreement between TK and K(P>0.05),larger differences between the two were associated with smaller central corneal thickness(P0.05),which both presented smaller MedAEs than others(all P0.05),and statistically larger percentages than the other eight formulas(P<0.05).Conclusions:Highly myopic eyes with thinner corneas tend to have larger differences between TK and *** XGboost enhancement calculator and RBF 3.0 formula using TK showed the most promising outcomes in highly myopic eyes.

关键词： High myopia Total keratometry Cataract surgery IOL power calculation

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

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