Mirror neuron system （MNS） represents one past decade, and it has been found to involve in multiple of the most important discoveries of cognitive neuroscience in the aspects of brain functions including action unde...Mirror neuron system （MNS） represents one past decade, and it has been found to involve in multiple of the most important discoveries of cognitive neuroscience in the aspects of brain functions including action understanding, imitation, language understanding, empathy, action prediction and speech evolution. This manuscript reviewed the function of MNS in action understanding as well as language evolution, and specifically assessed its roles as the bridge from body language to fluent speeches. Then we discussed the speech defects of autism patients due to the disruption of MNS. Finally, given that MNS is plastic in adult brain, we proposed MNS targeted therapy provides an efficient rehabilitation approach for brain damages conditions as well as autism patients.展开更多
The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent f...The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.展开更多
Previous studies have demonstrated that hand shadows may activate the motor cortex associated with the mirror neuron system in human brain. However, there is no evidence of activity of the human mirror neuron system d...Previous studies have demonstrated that hand shadows may activate the motor cortex associated with the mirror neuron system in human brain. However, there is no evidence of activity of the human mirror neuron system during the observation of intransitive movements by shadows and line drawings of hands. This study examined the suppression of electroencephalography mu waves （8-13 Hz） induced by observation of stimuli in 18 healthy students. Three stimuli were used： real hand actions, hand shadow actions and actions made by line drawings of hands. The results showed significant desynchronization of the mu rhythm （＂mu suppression＂） across the sensodmotor cortex （recorded at C3, Cz and C4）, the frontal cortex （recorded at F3, Fz and F4） and the central and right posterior parietal cortex （recorded at Pz and P4） under all three conditions. Our experimental findings suggest that the observation of ＂impoverished hand actions＂, such as intransitive movements of shadows and line drawings of hands, is able to activate widespread cortical areas related to the putative human mirror neuron system.展开更多
With the rapid development of computer science and artificial intelligence technology, the complexity and intelligence of the neural network models constructed by people have been greatly improved. When the complex ne...With the rapid development of computer science and artificial intelligence technology, the complexity and intelligence of the neural network models constructed by people have been greatly improved. When the complex neuron system is subjected to the impact of ＂catastrophic＂, its original characteristics may be changed, and the consequences are difficult to predict. Catastrophe dynamics mainly studies the source of the sudden violent change of nature and human society and its evolution. The impact of the system can be divided into endogenous and exogenous shocks. In this article, catastrophe theory is used to study the neuron system. Based on the mean field model of Hurst and Sornette, introducing the weight parameters, mathematical models are constructed to study the response characteristics of the neuron system in face of exogenous shocks, endogenous shocks, and integrated shocks. The time characteristics of the shock response of the neuron system are discussed too, such as the instantaneous and long-term response of the system in face of shocks, the different response forms according to the weight or linear superposition, and the influence of adjusting parameters on the neuron system. The research result shows that the authoritarian coefficient and weight coefficient have a very important influence on the response of neuron system; By adjusting the two coefficients, the purpose of disaster prevention, self-healing protection and response reducing can be well achieved.展开更多
Using the model of Hindmarsh Rose neurons, we study the synchronous behavior of the firing patterns in an uncoupled cell system. In this work, the membrane current Iext is selected as a controllable parameter, whose i...Using the model of Hindmarsh Rose neurons, we study the synchronous behavior of the firing patterns in an uncoupled cell system. In this work, the membrane current Iext is selected as a controllable parameter, whose initial values for all N cells are set to be near one of the bifurcation points randomly. It is found that the system will show un-synchronous state when the external stimuli is absent, otherwise, full synchrony will appear, even though without any coupling connection among these N neurons, indicating the occurrence of uncoupled synchrony. Moreover, similar behavior could also be observed when these neurons are set to be near other bifurcation points. The synchronous error is calculated for discussing this uncoupled synehrony behavior. Finally, we find that such synchrony may have some inherent relevance with the decrease of phase difference between different cells. Our results suggest that biological neuron systems may achieve an effective response to external feeble stimulus by the mode of uncoupled synchrony instead of only by the coupled scheme.展开更多
Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into ad...Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into adulthood, negatively impacting daily life in school, work, and social domains. A better understanding of the neural correlates of motor and imitation impairments in DCD holds the potential for informing development of treatment approaches to address these impairments. Although the disorder is assumed to be of neurological origin, little is known of the brain-based etiology of DCD. In recent years the discovery of a fronto-parietal circuit—known as the mirror neuron system—has enabled researchers to better understand imitation, general motor functions, and aspects of social cognition. Given its involvement in imitation and other motor functions, we propose that dysfunction in the mirror neuron system may underlie the characteristic impairments of DCD. We review literature pertaining to the mirror neuron system and develop a theory of disordered mirror neuron functioning in DCD. Finally, we review the limited neuroimaging literature available on neural correlates of DCD and show that the findings from those investigations are congruent with a mirror neuron system theory of DCD. Future research in this population should be designed to investigate specifically mirror neuron regions in individuals with DCD during skilled motor tasks and imitation in particular.展开更多
The reliability of the AI systems to the harsh space radiation is of great concerns with the increasing application in aerospace.Because of its neuromorphic device architecture and operation mode,low-power neuron chip...The reliability of the AI systems to the harsh space radiation is of great concerns with the increasing application in aerospace.Because of its neuromorphic device architecture and operation mode,low-power neuron chips have enormous potentials in resistance of single event effect,which is one of the most important failures of spacecraft caused by space radiation.In this work,a mixed-signal spiking neuron chip,named PAVLOV^([1]),has been studied at circuit and chip level with respect to its response to single event errors.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
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
Neuropathic pain,often featuring allodynia,imposes significant physical and psychological burdens on patients,with limited treatments due to unclear central mechanisms.Addressing this challenge remains a crucial unsol...Neuropathic pain,often featuring allodynia,imposes significant physical and psychological burdens on patients,with limited treatments due to unclear central mechanisms.Addressing this challenge remains a crucial unsolved issue in pain medicine.Our previous study,using protein kinase C gamma(PKCγ)-tdTomato mice,highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia.However,the regulatory mechanisms governing this circuit necessitate further elucidation.We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin(5-HT)facilitation system on spinal PKCγ neurons.Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_(2C) receptors,disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia.Inhibiting spinal 5-HT_(2C) receptors restored the feedforward inhibitory circuit,effectively preventing neuropathic allodynia.These insights offer promising therapeutic targets for neuropathic allodynia management,emphasizing the potential of spinal 5-HT_(2C) receptors as a novel avenue for intervention.展开更多
Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord ...Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.展开更多
Unwarranted death of neurons is a major cause of neurodegenerative diseases.Since mature neurons are postmitotic and do not replicate,their death usually constitutes an irreversible step in pathology.A logical strateg...Unwarranted death of neurons is a major cause of neurodegenerative diseases.Since mature neurons are postmitotic and do not replicate,their death usually constitutes an irreversible step in pathology.A logical strategy to prevent neurodegeneration would then be to save all neurons that are still alive,i.e.protecting the ones that are still healthy as well as trying to rescue the ones that are damaged and in the process of dying.Regarding the latter,recent experiments have indicated that the possibility of reversing the cell death process and rescuing dying cells is more significant than previously anticipated.In many situations,the elimination of the cell death trigger alone enables dying cells to spontaneously repair their damage,recover,and survive.In this review,we explore the factors,which determine the fate of neurons engaged in the cell death process.A deeper insight into cell death mechanisms and the intrinsic capacity of cells to recover could pave the way for novel therapeutic approaches to neurodegenerative diseases.展开更多
Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor...Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).展开更多
Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute cour...Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.展开更多
The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and...The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and single-cell transcriptomics of human medial ganglionic eminence(hMGE),a pivotal source of cortical and subpallial INs,and built the trajectories of hMGE-derived cells during brain development.We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types.展开更多
Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial ...Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial cells,mainly microglia and astrocytes.Microglia are the resident immune cells of the central nervous system,while astrocytes are the main support cells for neuronal functions but can also participate in neuroimmune responses.Both these glial cell types can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances;these can be pathology-associated abnormal structures,such as amyloidβproteins,or damage-associated molecular patterns released from injured cells,including their mitochondria.Once in the extracellular space,damage-associated molecular patterns act as ligands for specific pattern recognition receptors expressed by glia inducing their reactivity and neuroimmune responses.This review considers the following mitochondrial damage-associated molecular patterns:heme,cytochrome c,cardiolipin,adenosine triphosphate,mitochondrial DNA,mitochondrial transcription factor A,N-formyl peptides,and the tricarboxylic acid cycle metabolites:succinate,fumarate,and itaconate.We describe their well-established functions as damage-associated molecular patterns of the peripheral tissues before summarizing available evidence indicating these molecules may also play significant roles in the neuroimmune processes of the central nervous system.We highlight the pattern recognition receptors that mitochondrial damage-associated molecular patterns interact with and the cellular signaling mechanisms they modulate.Our review demonstrates that some mitochondrial damage-associated molecular patterns,such as cytochrome c,adenosine triphosphate,and mitochondrial transcription factor A,have already demonstrated significant effects on the central nervous system.In contrast,others including cardiolipin,mitochondrial DNA,N-formyl peptides,succinate,fumarate,and itaconate,will require additional studies corroborating their roles as damageassociated molecular patterns in the central nervous system.For all of the reviewed mitochondrial damage-associated molecular patterns,there is a shortage of studies using human cells and tissues,which is identified as a significant knowledge gap.We also assess the need for targeted research on the effects of mitochondrial damage-associated molecular patterns in the central nervous system pathologies where their roles are understudied.Such studies could identify novel treatment strategies for multiple neurodegenerative diseases,which are characterized by chronic neuroinflammation and currently lack effective therapies.展开更多
Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the ...Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.展开更多
V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating ene...V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.展开更多
Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinso...Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.展开更多
Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammat...Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.展开更多
基金Sci-ence Foundation of Ministry of Education of China (No.FBB011469)
文摘Mirror neuron system （MNS） represents one past decade, and it has been found to involve in multiple of the most important discoveries of cognitive neuroscience in the aspects of brain functions including action understanding, imitation, language understanding, empathy, action prediction and speech evolution. This manuscript reviewed the function of MNS in action understanding as well as language evolution, and specifically assessed its roles as the bridge from body language to fluent speeches. Then we discussed the speech defects of autism patients due to the disruption of MNS. Finally, given that MNS is plastic in adult brain, we proposed MNS targeted therapy provides an efficient rehabilitation approach for brain damages conditions as well as autism patients.
基金Science Foundation of Ministry of Education of China,No.FBB011469Hangzhou Municipal Natural Science Foundation, No.0737XP39Foundation of Hong Kong Special Administrative Region(RGC)
文摘The mirror neuron system （MNS） was first discovered in non-human primates; these neurons fire when a monkey performs an action or observes another monkey （or even some people） performing that same action. Recent findings have suggested that neural rehabilitation might be achieved through the activation of the MNS in patients after stroke. We propose two major mechanisms （one involving adult neurogenesis and another involving brain-derived neurotrophic factor） that may underlie the activation, modulation and experience-dependent plasticity in the MNS, for further study on promoting central nerve functional reconstruction and rehabilitation of patients with central nervous system injury.
基金supported by the grants from the National Natural Science Foundation of China,No.60775019,60970062 and 61173116the Research Fund for the Doctoral Program of Higher Education of China,No.201100702110014
文摘Previous studies have demonstrated that hand shadows may activate the motor cortex associated with the mirror neuron system in human brain. However, there is no evidence of activity of the human mirror neuron system during the observation of intransitive movements by shadows and line drawings of hands. This study examined the suppression of electroencephalography mu waves （8-13 Hz） induced by observation of stimuli in 18 healthy students. Three stimuli were used： real hand actions, hand shadow actions and actions made by line drawings of hands. The results showed significant desynchronization of the mu rhythm （＂mu suppression＂） across the sensodmotor cortex （recorded at C3, Cz and C4）, the frontal cortex （recorded at F3, Fz and F4） and the central and right posterior parietal cortex （recorded at Pz and P4） under all three conditions. Our experimental findings suggest that the observation of ＂impoverished hand actions＂, such as intransitive movements of shadows and line drawings of hands, is able to activate widespread cortical areas related to the putative human mirror neuron system.
基金Project(CX2016B142)supported by the Hunan Provincial Innovation Foundation for Postgraduate,China
文摘With the rapid development of computer science and artificial intelligence technology, the complexity and intelligence of the neural network models constructed by people have been greatly improved. When the complex neuron system is subjected to the impact of ＂catastrophic＂, its original characteristics may be changed, and the consequences are difficult to predict. Catastrophe dynamics mainly studies the source of the sudden violent change of nature and human society and its evolution. The impact of the system can be divided into endogenous and exogenous shocks. In this article, catastrophe theory is used to study the neuron system. Based on the mean field model of Hurst and Sornette, introducing the weight parameters, mathematical models are constructed to study the response characteristics of the neuron system in face of exogenous shocks, endogenous shocks, and integrated shocks. The time characteristics of the shock response of the neuron system are discussed too, such as the instantaneous and long-term response of the system in face of shocks, the different response forms according to the weight or linear superposition, and the influence of adjusting parameters on the neuron system. The research result shows that the authoritarian coefficient and weight coefficient have a very important influence on the response of neuron system; By adjusting the two coefficients, the purpose of disaster prevention, self-healing protection and response reducing can be well achieved.
基金Supported by the National Natural Science Foundation of China under Grant No 11047017the Natural Science Funds of Anhui Province under Grant No 1508085MA15
文摘Using the model of Hindmarsh Rose neurons, we study the synchronous behavior of the firing patterns in an uncoupled cell system. In this work, the membrane current Iext is selected as a controllable parameter, whose initial values for all N cells are set to be near one of the bifurcation points randomly. It is found that the system will show un-synchronous state when the external stimuli is absent, otherwise, full synchrony will appear, even though without any coupling connection among these N neurons, indicating the occurrence of uncoupled synchrony. Moreover, similar behavior could also be observed when these neurons are set to be near other bifurcation points. The synchronous error is calculated for discussing this uncoupled synehrony behavior. Finally, we find that such synchrony may have some inherent relevance with the decrease of phase difference between different cells. Our results suggest that biological neuron systems may achieve an effective response to external feeble stimulus by the mode of uncoupled synchrony instead of only by the coupled scheme.
文摘Primary impairments of developmental coordination disorder (DCD) include impairments in motor skill, motor learning, and imitation. Such difficulties present challenges for individuals with DCD and may persist into adulthood, negatively impacting daily life in school, work, and social domains. A better understanding of the neural correlates of motor and imitation impairments in DCD holds the potential for informing development of treatment approaches to address these impairments. Although the disorder is assumed to be of neurological origin, little is known of the brain-based etiology of DCD. In recent years the discovery of a fronto-parietal circuit—known as the mirror neuron system—has enabled researchers to better understand imitation, general motor functions, and aspects of social cognition. Given its involvement in imitation and other motor functions, we propose that dysfunction in the mirror neuron system may underlie the characteristic impairments of DCD. We review literature pertaining to the mirror neuron system and develop a theory of disordered mirror neuron functioning in DCD. Finally, we review the limited neuroimaging literature available on neural correlates of DCD and show that the findings from those investigations are congruent with a mirror neuron system theory of DCD. Future research in this population should be designed to investigate specifically mirror neuron regions in individuals with DCD during skilled motor tasks and imitation in particular.
文摘The reliability of the AI systems to the harsh space radiation is of great concerns with the increasing application in aerospace.Because of its neuromorphic device architecture and operation mode,low-power neuron chips have enormous potentials in resistance of single event effect,which is one of the most important failures of spacecraft caused by space radiation.In this work,a mixed-signal spiking neuron chip,named PAVLOV^([1]),has been studied at circuit and chip level with respect to its response to single event errors.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
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 the National Natural Science Foundation of China(81971058,82371226,82101295,82301398)the National Funded Postdoctoral Researcher Program(GZC20233585)The Boost Plan of Xijing Hospital(XJZT24QN25,XJZT25CX22).
文摘Neuropathic pain,often featuring allodynia,imposes significant physical and psychological burdens on patients,with limited treatments due to unclear central mechanisms.Addressing this challenge remains a crucial unsolved issue in pain medicine.Our previous study,using protein kinase C gamma(PKCγ)-tdTomato mice,highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia.However,the regulatory mechanisms governing this circuit necessitate further elucidation.We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin(5-HT)facilitation system on spinal PKCγ neurons.Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_(2C) receptors,disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia.Inhibiting spinal 5-HT_(2C) receptors restored the feedforward inhibitory circuit,effectively preventing neuropathic allodynia.These insights offer promising therapeutic targets for neuropathic allodynia management,emphasizing the potential of spinal 5-HT_(2C) receptors as a novel avenue for intervention.
基金supported by a grant from Ministry of Science and Technology China,No.2022ZD0204704(to WW)the National Natural Science Foundation of China,No.82301572(to XZ)the China Postdoctoral Science Foundation,No.2023M731202(to XZ)。
文摘Nonhuman primates are increasingly being used as animal models in neuroscience research.However,efficient neuronal tracing techniques for labeling motor neurons and primary sensory afferents in the monkey spinal cord are lacking.Here,by injecting the cholera toxin B subunit into the sciatic nerve of a rhesus monkey,we successfully labeled the motor neurons and primary sensory afferents in the lumbar and sacralspinal cord.Labeled alpha motor neurons were located in lamina IX of the L6–S1 segments,which innervate both flexors and extensors.The labeled primary sensory afferents were mainly myelinated Aβfibers that terminated mostly in laminae I and II of the L4–L7 segments.Together with the labeled proprioceptive afferents,the primary sensory afferents formed excitatory synapses with multiple types of spinal neurons.In summary,our methods successfully traced neuronal connections in the monkey spinal cord and can be used in spinal cord studies when nonhuman primates are used.
基金supported by the following foundations:“Stichting Oogfonds Nederland(No.2023-26)”the“Landelijke Stichting voor Blinden en Slechtzienden(No.2023-24)”that contributed through UitZicht,ZonMw grant(No.435005020)a grant of the Chinese Scholarship Council(No.201809110169)(to TGMFG,CPMR,and WY).
文摘Unwarranted death of neurons is a major cause of neurodegenerative diseases.Since mature neurons are postmitotic and do not replicate,their death usually constitutes an irreversible step in pathology.A logical strategy to prevent neurodegeneration would then be to save all neurons that are still alive,i.e.protecting the ones that are still healthy as well as trying to rescue the ones that are damaged and in the process of dying.Regarding the latter,recent experiments have indicated that the possibility of reversing the cell death process and rescuing dying cells is more significant than previously anticipated.In many situations,the elimination of the cell death trigger alone enables dying cells to spontaneously repair their damage,recover,and survive.In this review,we explore the factors,which determine the fate of neurons engaged in the cell death process.A deeper insight into cell death mechanisms and the intrinsic capacity of cells to recover could pave the way for novel therapeutic approaches to neurodegenerative diseases.
基金supported by the DGIST start-up funds from the Ministry of Science and ICT(2024010330)a National Research Foundation of Korea(NRF)grant funded by the Korea Government(MSIT)(No.RS-2024-00351442)(to TWK).
文摘Parkinson’s disease(PD)is the second most common neurodegenerative disorder.The progressive degeneration of dopamine(DA)producing neurons in the midbrain is the pathological hallmark,which leads to debilitating motor symptoms,including tremors,rigidity,and bradykinesia.Drug treatments,such as levodopa,provide symptomatic relief.However,they do not halt disease progression,and their effectiveness diminishes over time(reviewed in Poewe et al.,2017).
基金supported by the National Key Research and Development Program of China,No.2022YFC2703101(to YC)the National Natural Science Fundation of China,No.82371422(to YC)+1 种基金the National Innovation and Entrepreneurship Training Program for College Students,No.202310611408(to XW)the 1·3·5 Project for Disciplines of Excellence Clinical Research Fund,West China Hospital,Sichuan University,No.2023HXFH032(to YC)。
文摘Motor neuron diseases are sporadic or inherited fatal neurodegenerative conditions.They selectively affect the upper and/or lower motor neurons in the brain and spinal cord and feature a slow onset and a subacute course contingent upon the site of damage.The main types include amyotrophic lateral sclerosis,progressive muscular atrophy,primary lateral sclerosis,and progressive bulbar palsy,the pathological processes of which are largely identical,with the main disparity lying in the location of the lesions.Amyotrophic lateral sclerosis is the representative condition in this group of diseases,while other types are its variants.Hence,this article mainly focuses on the advancements and challenges in drug research for amyotrophic lateral sclerosis but also briefly addresses several other important degenerative motor neuron diseases.Although the precise pathogenesis remains elusive,recent advancements have shed light on various theories,including gene mutation,excitatory amino acid toxicity,autoimmunology,and neurotrophic factors.The US Food and Drug Administration has approved four drugs for use in delaying the progression of amyotrophic lateral sclerosis:riluzole,edaravone,AMX0035,and tofersen,with the latter being the most recent to receive approval.However,following several phaseⅢtrials that failed to yield favorable outcomes,AMX0035 has been voluntarily withdrawn from both the US and Canadian markets.This article presents a comprehensive summary of drug trials primarily completed between January 1,2023,and June 30,2024,based on data sourced from clinicaltrials.gov.Among these trials,five are currently in phaseⅠ,seventeen are in phaseⅡ,and eleven are undergoing phaseⅢevaluation.Notably,24 clinical trials are now investigating potential disease-modifying therapy drugs,accounting for the majority of the drugs included in this review.Some promising drugs being investigated in preclinical studies,such as ATH-1105,are included in our analysis,and another review in frontiers in gene therapy and immunotherapy has demonstrated their therapeutic potential for motor neuron diseases.This article was written to be an overview of research trends and treatment prospects related to motor neuron disease drugs,with the aim of highlighting the latest potentialities for clinical therapy.
文摘The number and diversity of inhibitory neurons(INs)increased substantially during mammalian brain evolution.However,the generative mechanisms of the vast repertoire of human INs remain elusive.We performed spatial and single-cell transcriptomics of human medial ganglionic eminence(hMGE),a pivotal source of cortical and subpallial INs,and built the trajectories of hMGE-derived cells during brain development.We identified spatiotemporally and molecularly segregated progenitor cell populations fated to produce distinct IN types.
基金supported by grants from the Jack Brown and Family Alzheimer’s Disease Research Foundationthe Natural Sciences and Engineering Research Council of Canada(No.2020-04407)+1 种基金the University of British Columbia Okanagan CampusThe authors also thank Gentmed SIA for financial assistance。
文摘Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial cells,mainly microglia and astrocytes.Microglia are the resident immune cells of the central nervous system,while astrocytes are the main support cells for neuronal functions but can also participate in neuroimmune responses.Both these glial cell types can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances;these can be pathology-associated abnormal structures,such as amyloidβproteins,or damage-associated molecular patterns released from injured cells,including their mitochondria.Once in the extracellular space,damage-associated molecular patterns act as ligands for specific pattern recognition receptors expressed by glia inducing their reactivity and neuroimmune responses.This review considers the following mitochondrial damage-associated molecular patterns:heme,cytochrome c,cardiolipin,adenosine triphosphate,mitochondrial DNA,mitochondrial transcription factor A,N-formyl peptides,and the tricarboxylic acid cycle metabolites:succinate,fumarate,and itaconate.We describe their well-established functions as damage-associated molecular patterns of the peripheral tissues before summarizing available evidence indicating these molecules may also play significant roles in the neuroimmune processes of the central nervous system.We highlight the pattern recognition receptors that mitochondrial damage-associated molecular patterns interact with and the cellular signaling mechanisms they modulate.Our review demonstrates that some mitochondrial damage-associated molecular patterns,such as cytochrome c,adenosine triphosphate,and mitochondrial transcription factor A,have already demonstrated significant effects on the central nervous system.In contrast,others including cardiolipin,mitochondrial DNA,N-formyl peptides,succinate,fumarate,and itaconate,will require additional studies corroborating their roles as damageassociated molecular patterns in the central nervous system.For all of the reviewed mitochondrial damage-associated molecular patterns,there is a shortage of studies using human cells and tissues,which is identified as a significant knowledge gap.We also assess the need for targeted research on the effects of mitochondrial damage-associated molecular patterns in the central nervous system pathologies where their roles are understudied.Such studies could identify novel treatment strategies for multiple neurodegenerative diseases,which are characterized by chronic neuroinflammation and currently lack effective therapies.
基金supported by the National Key Research and Development Program of China,No. 2023YFF0714200 (to CW)the National Natural Science Foundation of China,Nos. 82472038 and 82202224 (both to CW)+3 种基金the Shanghai Rising-Star Program,No. 23QA1407700 (to CW)the Construction Project of Shanghai Key Laboratory of Molecular Imaging,No. 18DZ2260400 (to CW)the National Science Foundation for Distinguished Young Scholars,No. 82025019 (to CL)the Greater Bay Area Institute of Precision Medicine (Guangzhou)(to CW)。
文摘Epilepsy is a leading cause of disability and mortality worldwide. However, despite the availability of more than 20 antiseizure medications, more than one-third of patients continue to experience seizures. Given the urgent need to explore new treatment strategies for epilepsy, recent research has highlighted the potential of targeting gliosis, metabolic disturbances, and neural circuit abnormalities as therapeutic strategies. Astrocytes, the largest group of nonneuronal cells in the central nervous system, play several crucial roles in maintaining ionic and energy metabolic homeostasis in neurons, regulating neurotransmitter levels, and modulating synaptic plasticity. This article briefly reviews the critical role of astrocytes in maintaining balance within the central nervous system. Building on previous research, we discuss how astrocyte dysfunction contributes to the onset and progression of epilepsy through four key aspects: the imbalance between excitatory and inhibitory neuronal signaling, dysregulation of metabolic homeostasis in the neuronal microenvironment, neuroinflammation, and the formation of abnormal neural circuits. We summarize relevant basic research conducted over the past 5 years that has focused on modulating astrocytes as a therapeutic approach for epilepsy. We categorize the therapeutic targets proposed by these studies into four areas: restoration of the excitation–inhibition balance, reestablishment of metabolic homeostasis, modulation of immune and inflammatory responses, and reconstruction of abnormal neural circuits. These targets correspond to the pathophysiological mechanisms by which astrocytes contribute to epilepsy. Additionally, we need to consider the potential challenges and limitations of translating these identified therapeutic targets into clinical treatments. These limitations arise from interspecies differences between humans and animal models, as well as the complex comorbidities associated with epilepsy in humans. We also highlight valuable future research directions worth exploring in the treatment of epilepsy and the regulation of astrocytes, such as gene therapy and imaging strategies. The findings presented in this review may help open new therapeutic avenues for patients with drugresistant epilepsy and for those suffering from other central nervous system disorders associated with astrocytic dysfunction.
基金support from various sources,including the National Natural Science Foundation of China(Grant Nos.81570774,82070872,92049118,and 82370854)the Junior Thousand Talents Program of China,and the Nanjing Medical University Startup Fund(All awarded to J.L.)support provided by Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(Grant No.JSSCTD2021)(All awarded to J.L.).
文摘V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.
基金financially supported by King Abdulaziz University,Deanship of Scientific Research(DSR)。
文摘Neuronal plasticity,the brain's ability to adapt structurally and functionally,is essential for learning,memory,and recovery from injuries.In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease,this plasticity is disrupted,leading to cognitive and motor deficits.This review explores the mechanisms of neuronal plasticity and its effect on Alzheimer's disease and Parkinson's disease.Alzheimer's disease features amyloid-beta plaques and tau tangles that impair synaptic function,while Parkinson's disease involves the loss of dopaminergic neurons affecting motor control.Enhancing neuronal plasticity offers therapeutic potential for these diseases.A systematic literature review was conducted using databases such as PubMed,Scopus,and Google Scholar,focusing on studies of neuronal plasticity in Alzheimer's disease and Parkinson's disease.Data synthesis identified key themes such as synaptic mechanisms,neurogenesis,and therapeutic strategies,linking molecular insights to clinical applications.Results highlight that targeting synaptic plasticity mechanisms,such as long-term potentiation and long-term depression,shows promise.Neurotrophic factors,advanced imaging techniques,and molecular tools(e.g.,clustered regularly interspaced short palindromic repeats and optogenetics)are crucial in understanding and enhancing plasticity.Current therapies,including dopamine replacement,deep brain stimulation,and lifestyle interventions,demonstrate the potential to alleviate symptoms and improve outcomes.In conclusion,enhancing neuronal plasticity through targeted therapies holds significant promise for treating neurodegenerative diseases.Future research should integrate multidisciplinary approaches to fully harness the therapeutic potential of neuronal plasticity in Alzheimer's disease and Parkinson's disease.
基金supported by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior-Brasil(CAPES)[Finance Code 001](to MGS)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico(CNPq)fellowship[research grants 309840/2022-8]。
文摘Neuroinflammation is an inflammatory response in the central nervous system associated with various neurological conditions.The inflammatory process is typically treated with non-steroidal and steroidal anti-inflammatory drugs,which have a range of serious adverse effects.As an alternative,naturally derived molecules such as quercetin and its derivatives show promising anti-inflammatory properties and beneficial effects on various physiological functions.Our objective was to synthesize the evidence on the anti-inflammatory effect of quercetin and its derivatives in in vivo models,in the face of neuroinflammatory insults induced by lipopolysaccharide,through a systematic review and meta-analysis.A search of the preclinical literature was conducted across four databases(Pub Med,Web of Science,Scielo,and Google Scholar).Studies were selected based on inclusion and exclusion criteria,assessed for methodological quality using CAMARADES,and risk of bias using the SYRCLE tool,and data were extracted from the studies.The quantitative assessment of quercetin effects on the expression of pro-inflammatory cytokines and microgliosis was performed through a meta-analysis.A total of 384 potentially relevant articles were identified,of which 11 studies were included in the analysis.The methodological quality was assessed,resulting in an average score of 5.8/10,and the overall risk of bias analysis revealed a lack of methodological clarity in most studies.Furthermore,through the meta-analysis,it was observed that treatment with quercetin statistically reduces pro-inflammatory cytokines,such as tumor necrosis factor alpha,interleukin 6,interleukin 1β(n=89;SMD=–2.00;95%CI:–3.29 to–0.71),and microgliosis(n=33;SMD=–2.56;95%CI:–4.07 to–1.10).In terms of underlying mechanisms,quercetin and its derivatives exhibit antioxidant and anti-apoptotic properties,possibly through the nuclear factor erythroid 2-related factor 2(Nrf2)/HO-1 pathways,increasing the expression of antioxidant enzymes and reducing reactive species,and modulating the caspase pathway,increasing levels of anti-apoptotic proteins and decreasing proapoptotic proteins.Quercetin and its derivatives exhibit highly pleiotropic actions that simultaneously contribute to preventing neuroinflammation.However,despite promising results in animal models,future directions should focus on well-designed clinical studies to assess the safety,bioavailability,and efficacy of quercetin and its derivatives in humans.Additionally,standardization of methods and dosages in studies is crucial to ensure consistency of findings and optimize their application in clinical settings.
