Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzh...The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.展开更多
The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiot...The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).展开更多
Microglia have been recognized as a unique cell population in the central nervous system(CNS)for more than a century[1].However,it was not until 2010 that their developmental origin was clarified.Rather than arising f...Microglia have been recognized as a unique cell population in the central nervous system(CNS)for more than a century[1].However,it was not until 2010 that their developmental origin was clarified.Rather than arising from the neuroectoderm,microglia are derived from erythromyeloid progenitors in the embryonic yolk sac[2].展开更多
The global aging crisis has increased the prevalence of skeletal disorders,necessitating innovative therapeutic strategies.This review employs the brain-bone axis(BBA)framework to examine the role of the sympathetic n...The global aging crisis has increased the prevalence of skeletal disorders,necessitating innovative therapeutic strategies.This review employs the brain-bone axis(BBA)framework to examine the role of the sympathetic nervous system(SNS)in bone metabolism.The research systematically elucidates the molecular mechanisms by which the SNS mediates signaling pathways through neurofibers and neurotransmitters,such as norepinephrine,dopamine,neuropeptide Y,and leptin,regulating interactions between bone-related cells to maintain skeletal homeostasis.It also identifies the pathological associations between the dysregulation of these pathways and the progression of bone-related conditions,such as osteoporosis,osteoarthritis,and intervertebral disc degeneration.By integrating current evidence,we identify novel therapeutic targets within the BBA and propose neuro-centric intervention strategies to mitigate skeletal diseases.This review deepens the understanding of neuro-skeletal interactions and lays a foundation for innovative treatments for bone-related pathologies.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central ne...Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
Acupuncture,a therapeutic practice rooted in traditional Chinese medicine and integrated with modern neuroscience,achieves its effects by stimulating sensory nerves at specific anatomical points known as acupoints.Thi...Acupuncture,a therapeutic practice rooted in traditional Chinese medicine and integrated with modern neuroscience,achieves its effects by stimulating sensory nerves at specific anatomical points known as acupoints.This review systematically explores the therapeutic components of acupuncture,emphasizing the interplay between sensory nerve characteristics and neural signaling pathways.Key factors such as acupoint location,needling depth,stimulation intensity,retention time,and the induction of sensations(e.g.,Deqi)are analyzed for their roles in neural activation and clinical outcomes.The review highlights how variations in spinal segment targeting,tissue-specific receptor activation,and stimulation modalities(e.g.,manual acupuncture,electroacupuncture,moxibustion)influence therapeutic effects.Emerging evidence underscores the significance of ion channels,dermatomes,myotomes,and genespecific pathways in mediating systemic effects.Additionally,the differential roles of mechanical,thermal and nociceptive stimuli and the temporal dynamics of sensory and immune responses are addressed.While insights from animal models have advanced our understanding,their translation to clinical practice requires further investigation.This comprehensive review identifies critical parameters for optimizing acupuncture therapy,advocating for individualized treatment strategies informed by neuroanatomical and neurophysiological principles,ultimately enhancing its precision and efficacy in modern medicine.展开更多
The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals i...The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated,the intimate relationship between the central nervous system and bone remains less understood,yet it has emerged as a hot topic in the bone field.In this review,we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism,either intact or after injury.First,we explored mechanistic studies linking specific brain nuclei with bone homeostasis,including the ventromedial hypothalamus,arcuate nucleus,paraventricular hypothalamic nucleus,amygdala,and locus coeruleus.We then focused on the characteristics of bone innervation and nerve subtypes,such as sensory,sympathetic,and parasympathetic nerves.Moreover,we summarized the molecular features and regulatory functions of these nerves.Finally,we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration.Therefore,considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process,ultimately benefiting future clinical translation.展开更多
Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic...Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the c...In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Physiology is an important basic course for medical majors.The content of the nervous system is abstract,the theories are profound,the knowledge is updated rapidly,and it is most closely connected with clinical practi...Physiology is an important basic course for medical majors.The content of the nervous system is abstract,the theories are profound,the knowledge is updated rapidly,and it is most closely connected with clinical practice.Students generally report difficulties in understanding,resulting in low learning interest.To improve teaching quality,this study has attempted to organically integrate clinical cases,scientific research methods and classroom teaching in the teaching of the nervous system,and constructed a“clinical-research-teaching”trinity teaching model.With“clinical problem-driven,scientific research thinking-driven,teaching scenario reconstruction”as the main line,real cases,scientific research examples and cutting-edge research progress in neuroscience were introduced to stimulate students’learning interest and cultivate their scientific thinking and clinical application abilities.Practice has shown that this model can effectively improve teaching effectiveness and students’comprehensive quality.Compared with the traditional teaching model,this teaching model significantly improved students’final exam scores(p<0.01),scores of the Critical Thinking Disposition Inventory(p<0.01),and the number of approved college students’innovation and entrepreneurship projects.It is proved that the“trinity”teaching model can stimulate learning interest,cultivate integrated medical talents,and is an effective way to achieve in-depth connection between basic medicine and clinical practice.展开更多
The nervous system is the dominant regulatory system in the human body.The traditional theory is that tumors lack innervation.However,an increasing number of studies have shown complex bidirectional interactions betwe...The nervous system is the dominant regulatory system in the human body.The traditional theory is that tumors lack innervation.However,an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system.Globally,colorectal cancer(CRC)is the third most common cancer.With the rise of tumor neuroscience,the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention.However,there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC.This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC,focusing on the following areas:(1)Effects of the nervous system on colon cancer.(2)Effects of CRC on the nervous system.(3)Treatment of CRC associated with the nervous system.展开更多
Myelin formation is considered the last true“invention”in the evolution of vertebrate nervous system cell structure.The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is th...Myelin formation is considered the last true“invention”in the evolution of vertebrate nervous system cell structure.The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement,sensation,and cognitive function.As a key structure in the brain,white matter is the gathering place of myelin.However,with age,white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes,causing serious neurological and cognitive disorders.Despite the extensive time and effort invested in exploring myelination and its functions,numerous unresolved issues and challenges persist.In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system(CNS)diseases and even mental illnesses.In this study,we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS,delving into its formation process.Specifically,we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension.The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.展开更多
Casein kinase 1(CK1)is an important member of the serine/threonine protein kinase family,playing a crucial role in various cellular processes,including cell cycle regulation,signal transduction,DNA repair,and circadia...Casein kinase 1(CK1)is an important member of the serine/threonine protein kinase family,playing a crucial role in various cellular processes,including cell cycle regulation,signal transduction,DNA repair,and circadian rhythm control.CK1 is also essential in the nervous system,where it regulates neuronal growth,differentiation,and synaptic plasticity.Studies have shown that CK1δ phosphorylates neuron-specific proteins to regulate axonal growth and synaptogenesis.Primary cilia are non-motile microtubule structures present on the surface of most mammalian cells.Recent studies have revealed their multiple roles in cellular physiology and development,and dysfunction of cilia can impact the development and function of the nervous system.CK1 has an important role in the formation and function of primary cilia.By regulating various signaling pathways and the phosphorylation status of proteins,CK1 affects the generation,maintenance,and signaling transduction of cilia.In this review,the relationship between CK1,primary cilia,and the nervous system was explored,focusing on how CK1 influences cilia to regulate the structure and function of the nervous system.展开更多
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by ANR(ANR-21CE16-0008-01)ANR(ANR-21-CE16-0008-02 and ANR-23CE52-0007)+1 种基金UNADEV(A22018CS)(to HN)UNADEV(A22020CS)(to SB)。
文摘The mature central nervous system(CNS,composed of the brain,spinal cord,olfactory and optic nerves)is unable to regenerate spontaneously after an insult,both in the cases of neurodegenerative diseases(for example Alzheimer's or Parkinson's disease)or traumatic injuries(such as spinal cord lesions).In the last 20 years,the field has made significant progress in unlocking axon regrowth.
基金supported by the European Union-Next Generation EU,Mission 4 Component 1,Project Title:“Gut and Neuro Muscular system:investigating the impact of microbiota on nerve regeneration and muscle reinnervation after peripheral nerve injury”,CUP D53D23007770006,MUR:20227YB93W,to GR。
文摘The gut microbiota:The human body is colonized by a diverse and complex microbial community–including bacteria,viruses,archaea,and unicellular eukaryotes–that plays a central role in human wellbeing.Indeed,microbiota is crucial for several functions,including host metabolism,physiology,maintenance of the intestinal epithelial integrity,nutrition,and immune function,earning it the designation of a“vital organ”(Guinane and Cotter,2013).
基金supported in part by National Science and Technology Major Project of National Health Commission of China(2023ZD0520300)the National Natural Science Foundation of China(32130037 and 32370953)the Tsinghua University Initiative Scientific Research Program,SXMU-Tsinghua Collaborative Innovation Center for Frontier Medicine and the Research Fund of Vanke School of Public Health,Tsinghua University.H.Q.is a New Cornerstone Investigator.
文摘Microglia have been recognized as a unique cell population in the central nervous system(CNS)for more than a century[1].However,it was not until 2010 that their developmental origin was clarified.Rather than arising from the neuroectoderm,microglia are derived from erythromyeloid progenitors in the embryonic yolk sac[2].
基金funded by Shaoxing University’s enterprise important horizontal topic(No.2024USXH287)the Graduate research project of Shaoxing University(Nos.Y20240280)。
文摘The global aging crisis has increased the prevalence of skeletal disorders,necessitating innovative therapeutic strategies.This review employs the brain-bone axis(BBA)framework to examine the role of the sympathetic nervous system(SNS)in bone metabolism.The research systematically elucidates the molecular mechanisms by which the SNS mediates signaling pathways through neurofibers and neurotransmitters,such as norepinephrine,dopamine,neuropeptide Y,and leptin,regulating interactions between bone-related cells to maintain skeletal homeostasis.It also identifies the pathological associations between the dysregulation of these pathways and the progression of bone-related conditions,such as osteoporosis,osteoarthritis,and intervertebral disc degeneration.By integrating current evidence,we identify novel therapeutic targets within the BBA and propose neuro-centric intervention strategies to mitigate skeletal diseases.This review deepens the understanding of neuro-skeletal interactions and lays a foundation for innovative treatments for bone-related pathologies.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘Copper is a transition metal and an essential element for the organism,as alterations in its homeostasis leading to metal accumulation or deficiency have pathological effects in several organs,including the central nervous system.Central copper dysregulations have been evidenced in two genetic disorders characterized by mutations in the copper-ATPases ATP7A and ATP7B,Menkes disease and Wilson’s disease,respectively,and also in multifactorial neurological disorders such as Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and multiple sclerosis.This review summarizes current knowledge about the role of copper in central nervous system physiology and pathology,reports about unbalances in copper levels and/or distribution under disease,describes relevant animal models for human disorders where copper metabolism genes are dysregulated,and discusses relevant therapeutic approaches modulating copper availability.Overall,alterations in copper metabolism may contribute to the etiology of central nervous system disorders and represent relevant therapeutic targets to restore tissue homeostasis.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Korea government(MSIT)(No.NRF-2020R1C1C1004107)。
文摘Acupuncture,a therapeutic practice rooted in traditional Chinese medicine and integrated with modern neuroscience,achieves its effects by stimulating sensory nerves at specific anatomical points known as acupoints.This review systematically explores the therapeutic components of acupuncture,emphasizing the interplay between sensory nerve characteristics and neural signaling pathways.Key factors such as acupoint location,needling depth,stimulation intensity,retention time,and the induction of sensations(e.g.,Deqi)are analyzed for their roles in neural activation and clinical outcomes.The review highlights how variations in spinal segment targeting,tissue-specific receptor activation,and stimulation modalities(e.g.,manual acupuncture,electroacupuncture,moxibustion)influence therapeutic effects.Emerging evidence underscores the significance of ion channels,dermatomes,myotomes,and genespecific pathways in mediating systemic effects.Additionally,the differential roles of mechanical,thermal and nociceptive stimuli and the temporal dynamics of sensory and immune responses are addressed.While insights from animal models have advanced our understanding,their translation to clinical practice requires further investigation.This comprehensive review identifies critical parameters for optimizing acupuncture therapy,advocating for individualized treatment strategies informed by neuroanatomical and neurophysiological principles,ultimately enhancing its precision and efficacy in modern medicine.
基金supported by the Health&Medical Research Fund(18190481)the General Research Fund(14120520).
文摘The skeleton is innervated by different types of nerves and receives signaling from the nervous system to maintain homeostasis and facilitate regeneration or repair.Although the role of peripheral nerves and signals in regulating bone homeostasis has been extensively investigated,the intimate relationship between the central nervous system and bone remains less understood,yet it has emerged as a hot topic in the bone field.In this review,we discussed clinical observations and animal studies that elucidate the connection between the nervous system and bone metabolism,either intact or after injury.First,we explored mechanistic studies linking specific brain nuclei with bone homeostasis,including the ventromedial hypothalamus,arcuate nucleus,paraventricular hypothalamic nucleus,amygdala,and locus coeruleus.We then focused on the characteristics of bone innervation and nerve subtypes,such as sensory,sympathetic,and parasympathetic nerves.Moreover,we summarized the molecular features and regulatory functions of these nerves.Finally,we included available translational approaches that utilize nerve function to improve bone homeostasis and promote bone regeneration.Therefore,considering the nervous system within the context of neuromusculoskeletal interactions can deepen our understanding of skeletal homeostasis and repair process,ultimately benefiting future clinical translation.
基金funded by Basic Research Program of Shanghai,No.20JC1412200(to JW)the National Key Research and Development Program of China,No.2020YFA0113000(to RCZ)。
文摘Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous system.Lipid droplet formation begins with the synthesis of neutral lipids in the endoplasmic reticulum.Previously,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous system.In addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress responses.Furthermore,lipid droplets exhibit specific functions in neurons and glial cells.Dysregulation of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system diseases.This review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and functions.Additionally,it will explore the association between lipid droplets and neurodegenerative disorders.Understanding the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
基金supported by Ohio State Start Up FundNational Institutes of Health(NIH)+12 种基金Department of Defense(DoD)Wings for Life Spinal Cord Research Foundation,Wings for Life Spinal Cord Research Foundation(Austria)California Institute of Regenerative Medicine(CIRM)International Spinal Research Trust(United Kingdom)Stanford University Bio-X Program Interdisciplinary Initiatives Seed Grant IIP-7Dennis Chan FoundationKlein Family FundLucile Packard Foundation for Children's HealthStanford Institute for Neuro-Innovation and Translational Neurosciences(SINTN)Saunders Family Neuroscience FundJames Doty Neurosurgery FundHearst Neuroscience FundEileen Bond Research Fund(to GP)。
文摘In recent years,the progression of stem cell therapies has shown great promise in advancing the nascent field of regenerative medicine.Considering the non-regenerative nature of the mature central nervous system,the concept that“blank”cells could be reprogrammed and functionally integrated into host neural networks remained intriguing.Previous work has also demonstrated the ability of such cells to stimulate intrinsic growth programs in post-mitotic cells,such as neurons.While embryonic stem cells demonstrated great potential in treating central nervous system pathologies,ethical and technical concerns remained.These barriers,along with the clear necessity for this type of treatment,ultimately prompted the advent of induced pluripotent stem cells.The advantage of pluripotent cells in central nervous system regeneration is multifaceted,permitting differentiation into neural stem cells,neural progenitor cells,glia,and various neuronal subpopulations.The precise spatiotemporal application of extrinsic growth factors in vitro,in addition to microenvironmental signaling in vivo,influences the efficiency of this directed differentiation.While the pluri-or multipotency of these cells is appealing,it also poses the risk of unregulated differentiation and teratoma formation.Cells of the neuroectodermal lineage,such as neuronal subpopulations and glia,have been explored with varying degrees of success.Although the risk of cancer or teratoma formation is greatly reduced,each subpopulation varies in effectiveness and is influenced by a myriad of factors,such as the timing of the transplant,pathology type,and the ratio of accompanying progenitor cells.Furthermore,successful transplantation requires innovative approaches to develop delivery vectors that can mitigate cell death and support integration.Lastly,host immune responses to allogeneic grafts must be thoroughly characterized and further developed to reduce the need for immunosuppression.Translation to a clinical setting will involve careful consideration when assessing both physiologic and functional outcomes.This review will highlight both successes and challenges faced when using human induced pluripotent stem cell-derived cell transplantation therapies to promote endogenous regeneration.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
基金General Program of Guangdong Provincial Natural Science Foundation(Project No.:2214050002848)College Students’Innovation and Entrepreneurship Projects(Project No.:202310582018,622A0243,S202410582051)+2 种基金Key Teaching Reform Project of Jiaying University(Project No.:423A0613)2025 Teaching Quality and Teaching Reform Project of Jiaying University(Project No.:27)2023 University-level Teaching Quality and Teaching Reform Project(Project No.:ZLGC2023101)。
文摘Physiology is an important basic course for medical majors.The content of the nervous system is abstract,the theories are profound,the knowledge is updated rapidly,and it is most closely connected with clinical practice.Students generally report difficulties in understanding,resulting in low learning interest.To improve teaching quality,this study has attempted to organically integrate clinical cases,scientific research methods and classroom teaching in the teaching of the nervous system,and constructed a“clinical-research-teaching”trinity teaching model.With“clinical problem-driven,scientific research thinking-driven,teaching scenario reconstruction”as the main line,real cases,scientific research examples and cutting-edge research progress in neuroscience were introduced to stimulate students’learning interest and cultivate their scientific thinking and clinical application abilities.Practice has shown that this model can effectively improve teaching effectiveness and students’comprehensive quality.Compared with the traditional teaching model,this teaching model significantly improved students’final exam scores(p<0.01),scores of the Critical Thinking Disposition Inventory(p<0.01),and the number of approved college students’innovation and entrepreneurship projects.It is proved that the“trinity”teaching model can stimulate learning interest,cultivate integrated medical talents,and is an effective way to achieve in-depth connection between basic medicine and clinical practice.
基金supported by the National Natural Science Foundation of China(81901324)the Youth Innovation Technology Project of Higher School in Shandong Province(2023KJ261).
文摘The nervous system is the dominant regulatory system in the human body.The traditional theory is that tumors lack innervation.However,an increasing number of studies have shown complex bidirectional interactions between tumors and the nervous system.Globally,colorectal cancer(CRC)is the third most common cancer.With the rise of tumor neuroscience,the role of nervous system imbalances in the occurrence and development of CRC has attracted increasing amounts of attention.However,there are still many gaps in the research on the interactions and mechanisms involved in the nervous system in CRC.This article systematically reviews emerging research on the bidirectional relationships between the nervous system and CRC,focusing on the following areas:(1)Effects of the nervous system on colon cancer.(2)Effects of CRC on the nervous system.(3)Treatment of CRC associated with the nervous system.
基金supported by the National Natural Science Foundation of China(No.U21A20400)the Natural Science Foundation of Beijing(No.8217153264)the Key Project of Beijing University of Chinese Medicine(No.2022-JYB-JBZR-004),China.
文摘Myelin formation is considered the last true“invention”in the evolution of vertebrate nervous system cell structure.The rapid jumping pulse propagation achieved by myelin enables the high conduction speed that is the basis of human movement,sensation,and cognitive function.As a key structure in the brain,white matter is the gathering place of myelin.However,with age,white matter-associated functions become abnormal and a large number of myelin sheaths undergo degenerative changes,causing serious neurological and cognitive disorders.Despite the extensive time and effort invested in exploring myelination and its functions,numerous unresolved issues and challenges persist.In-depth exploration of the functional role of myelin may bring new inspiration for the treatment of central nervous system(CNS)diseases and even mental illnesses.In this study,we conducted a comprehensive examination of the structure and key molecules of the myelin in the CNS,delving into its formation process.Specifically,we propose a new hypothesis regarding the source of power for myelin expansion in which membrane compaction may serve as a driving force for myelin extension.The implications of this hypothesis could provide valuable insights into the pathophysiology of diseases involving myelin malfunction and open new avenues for therapeutic intervention in myelin-related disorders.
文摘Casein kinase 1(CK1)is an important member of the serine/threonine protein kinase family,playing a crucial role in various cellular processes,including cell cycle regulation,signal transduction,DNA repair,and circadian rhythm control.CK1 is also essential in the nervous system,where it regulates neuronal growth,differentiation,and synaptic plasticity.Studies have shown that CK1δ phosphorylates neuron-specific proteins to regulate axonal growth and synaptogenesis.Primary cilia are non-motile microtubule structures present on the surface of most mammalian cells.Recent studies have revealed their multiple roles in cellular physiology and development,and dysfunction of cilia can impact the development and function of the nervous system.CK1 has an important role in the formation and function of primary cilia.By regulating various signaling pathways and the phosphorylation status of proteins,CK1 affects the generation,maintenance,and signaling transduction of cilia.In this review,the relationship between CK1,primary cilia,and the nervous system was explored,focusing on how CK1 influences cilia to regulate the structure and function of the nervous system.
