The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predomina...The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to provide a critical overview about neuroplasticity, depression and antidepressant drugs, a detailed Pubmed/Medline, Scopus, Psyc Lit, and Psyc Info search to identify all papers and book chapters during the period between 1980 and 2011 was performed. Pathological stress and depression determine relevant brain changes such as loss of dendritic spines and synapses, dendritic atrophy as well as reduction of glial cells(both in number and size) in specific areas such as the hippocampus and prefrontal cortex. An increased dendritic arborisation and synaptogenesis may instead be observed in the amygdala as a consequence of depression and stress-related disorders. While hippocampal and prefrontal functioning was impaired, amygdala functioning was abnormally amplified. Most of molecular abnormalities and biological changes of aberrant neuroplasticity may be explained by the action of glutamate. Antidepressant treatment is associated with neurogenesis, gliogenesis, dendritic arborisation, new synapse formation and cell survival both in the hippocampus and prefrontal cortex. Antidepressants(ADs) induce neuroplasticity mechanisms reversing the pathological effects of depression and stress-related disorders. The neuroplasticity hypothesis may explain the therapeutic and prophylactic action of ADs representing a new innovative approach to the pathophysiology of depression and stress-related disorders.展开更多
Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with com...Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).展开更多
Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led ...Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants.One such novel antidepressant is ketamine,which has demonstrated both clinically promising results and contributed to new explanatory models of depression,including the potential role of neuroplasticity in depression.Early clinical trials are now showing promising results of serotonergic psychedelics for depression;however,their mechanism of action remains poorly understood.This paper seeks to review the effect of depression,classic antidepressants,ketamine,and serotonergic psychedelics on markers of neuroplasticity at a cellular,molecular,electrophysiological,functional,structural,and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.展开更多
Exploratory studies developed at several neurosciences laboratories at universities around the world show us through the experience that there is a biological process called neuroplasticity. Because of this oldest con...Exploratory studies developed at several neurosciences laboratories at universities around the world show us through the experience that there is a biological process called neuroplasticity. Because of this oldest concept about the neuronal formation, scientists also thought that if a particular area of the adult brain was damaged, the nerve cells could not form new connections and the functions controlled by this field of the brain would be permanently lost or could not be regenerate. However, studies have overturned this old view, and currently, scientists recognize that the brain continues to reorganize itself by forming new neural connections during the life. This phenomenon is called neuroplasticity that refers to the potential which the brain should be reorganized by creating new neural pathways to adapt, as it needs.展开更多
Neuroplasticity is a condition that is present from birth, being found in the central and peripheral nervous system, in both physiological and pathological terms. Based on the findings, therapeutic and non-therapeutic...Neuroplasticity is a condition that is present from birth, being found in the central and peripheral nervous system, in both physiological and pathological terms. Based on the findings, therapeutic and non-therapeutic attempts were tested on spinal cord trauma to recover locomotor function below the level of the injury. The work defined and showed other forms of the term neuroplasticity, talk about some pathological and non-pathological conditions, and, finally, show neuroplasticity and some of its treatments in the spinal cord injury process. A narrative literature review from 2000 to 2020 of the PubMed platform was conducted and analysis of two books for the elaboration of this <span>work. Animal/human studies were included that addressed pathologies,</span> forms of treatment for spinal trauma, and qualis from B1 to A1. Pre-2000 articles, which addressed neuroplasticity only to understand the molecular mechanisms and articles that were not in English, were excluded. As a result, the main molecules and structures that inhibit neuroplasticity were found, and, based on their knowledge, forms of treatments were developed to inhibit these molecules and structures to assist in neuroplasticity and assist in possible functional recovery. It can be concluded that the physiological barriers are already being overcome by the most recent forms of treatment and that soon new studies may propose a form of treatment that is protocoled for all patients.展开更多
Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition.The clinical picture is dominated by upper and lower motor neuron degeneration,but extra-motor pathology is increasingly recognized,in...Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition.The clinical picture is dominated by upper and lower motor neuron degeneration,but extra-motor pathology is increasingly recognized,including cerebellar pathology.Post-mortem and neuroimaging studies primarily focus on the chara cterization of supratentorial disease,des pite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis.Cardinal clinical features of amyotrophic lateral sclerosis,such as dysarthria,dysphagia,cognitive and behavioral deficits,saccade abnormalities,gait impairment,respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar pathology.This review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral scle rosis.Structural imaging studies consistently capture cerebellar grey matter volume reductions,diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alte rations and functional imaging studies commonly report increased functional connectivity with supratentorial regions.Increased functional connectivity is commonly interpreted as evidence of neuro plasticity representing compensatory processes despite the lack of post-mortem validation.There is a scarcity of post-mortem studies focusing on cerebellar alte rations,but these detect pTDP-43 in cerebellar nuclei.Ce rebellar pathology is an overloo ked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms,wides p read connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.展开更多
The rehabilitation of musculoskeletal dysfunctions(MSD)such as osteoarthritis,anterior cruciate ligament injuries and low back pain focuses on symptomatic management of pain followed by stretching and strengthening.Ho...The rehabilitation of musculoskeletal dysfunctions(MSD)such as osteoarthritis,anterior cruciate ligament injuries and low back pain focuses on symptomatic management of pain followed by stretching and strengthening.However,these interventions focus just on symptomatic pain management and addressing musculoskeletal impairments.But it has been found that neuroplastic changes continue to occur throughout these pathologies and sometimes even are persistent,as conventional rehabilitation doesn’t focus on these changes therefore chances of reinjury increase.Therefore this article discusses underlying neuroplastic changes associated with MSD and neuroplasticity-based interventions for better clinical outcomes.展开更多
The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regenerati...The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regeneration in response to brain diseases and injury. The occurrence of adult neurogenesis has unequivocally been witnessed in human subjects, experimental and wildlife research including rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in which generation of neuroblasts namely, neuroblastosis appears to be an integral process that occur in the limbic system and basal ganglia in addition to the canonical neurogenic niches. Neuroblastosis can be regulated by various factors and contributes to different functions of the brain. The characteristics and fate of neuroblasts have been found to be different among mammals regardless of their cognitive functions. Recently, regulation of neuroblastosis has been proposed for the sensorimotor interface and regenerative neuroplasticity of the adult brain. Hence, the understanding of adult neurogenesis at the functional level of neuroblasts requires a great scientific attention. Therefore, this mini-review provides a glimpse into the conceptual development of neuroplasticity, discusses the possible role of different types of neuroblasts and signifies neuroregenerative failure as a potential cause of dementia.展开更多
Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neu...Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cognitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.展开更多
Gait disorders drastically affect the quality of life of stroke survivors,making post-stroke rehabilitation an important research focus.Noninvasive brain stimulation has potential in facilitating neuroplasticity and i...Gait disorders drastically affect the quality of life of stroke survivors,making post-stroke rehabilitation an important research focus.Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment.However,a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized.We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery,and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery.While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity,it evolves over time,is idiosyncratic,and may develop maladaptive elements.Furthermore,noninvasive brain stimulation has limited reach capability and is facilitative-only in nature.Therefore,we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques.Additionally,when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors,stimulation montages should be customized according to the specific types of neuroplasticity found in each individual.This could be done using multiple mapping techniques.展开更多
In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible ...In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.展开更多
Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injur...Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.展开更多
Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the ...Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.展开更多
BACKGROUND Anosmia was one of the main symptoms of coronavirus disease 2019(COVID-19).A psychiatric history(i.e.,depression)may be an independent contributor to the risk of COVID-19 diagnosis,and COVID-19 survivors ap...BACKGROUND Anosmia was one of the main symptoms of coronavirus disease 2019(COVID-19).A psychiatric history(i.e.,depression)may be an independent contributor to the risk of COVID-19 diagnosis,and COVID-19 survivors appear to have an increased risk of neuropsychiatric sequelae(bidirectional association).AIM To compare the rate of psychiatric disorder among post-COVID patients without anosmia vs patients with persistent olfactory complaints.METHODS We conducted a prospective case control study from March 2020 to May 2021.Patients recruited at the ENT department of Nice University Hospital had a subjective olfactory complaint(visual analogue scale)for over 6 wk and a molecular or CT-proven severe acute respiratory syndrome coronavirus 2 diagnosis confirmed by serology.Post-COVID patients without persistent olfactory disorders were recruited at the university hospital infectiology department.Psychiatric medical histories were collected by a psychiatrist during the assessments.RESULTS Thirty-four patients with post-COVID-19 olfactory complaints were included in the first group of the study.Fifty percent of the patients were female(n=17).The group’s mean age was 40.5±12.9 years.The control group included 32 participants,of which 34.4%were female(n=11),and had a mean age of 61.2±12.2 years.The rate of psychiatric disorder among post-COVID patients with olfactory complaints was significatively higher(41.7%)than among patients without(18.8%)(χ2=5.9,P=0.015).CONCLUSION The presence of a psychiatric history may constitute a potential risk factor for the development of long COVID due to persistent anosmia.It therefore seems important to establish reinforced health monitoring after a COVID 19 infection in at-risk patients.Further prospective,translational,and collaborative studies are needed to extrapolate these results to the general population.展开更多
背景:抑制控制和药物渴求是评估甲基苯丙胺成瘾者药物戒断的核心要素,备受学界关注。众所周知,要彻底实现对药物成瘾的戒断,恢复吸毒者受损的抑制控制功能,有效降低对药物的渴求是关键。目的:旨在通过系统分析运动与甲基苯丙胺戒断者抑...背景:抑制控制和药物渴求是评估甲基苯丙胺成瘾者药物戒断的核心要素,备受学界关注。众所周知,要彻底实现对药物成瘾的戒断,恢复吸毒者受损的抑制控制功能,有效降低对药物的渴求是关键。目的:旨在通过系统分析运动与甲基苯丙胺戒断者抑制控制和药物渴求的关系,找出促进甲基苯丙胺成瘾戒断的有效运动干预方案,并进一步探究运动作用的内在机制,以期为未来运动运用于毒品戒断提供理论上的支持和应用上的参考。方法:通过检索中国知网、万方、维普、Web of Science及PubMed数据库,中文检索词为“运动,体育锻炼,甲基苯丙胺,抑制功能,渴求度,成瘾”等,英文检索词为“Sport*,Exercise,Methamphetamine,Drug craving,Executive function,Addiction”等,依据纳入和排除标准对文献进行筛选,最终获得目标文献65篇进行综述分析。结果与结论:①运动对甲基苯丙胺戒断者抑制控制方面,急性和长期中等强度有氧运动或急性中高强度间歇训练均能够显著提升甲基苯丙胺戒断者抑制控制能力,对于长期有氧运动而言,有氧操课练习或全身性的综合练习效果更佳,若运动形式为功率自行车,建议增加运动干预频次。②运动对甲基苯丙戒断者药物渴求度方面,急性中等强度有氧运动和抗阻力训练或长期中等强度、高强度或递增负荷的有氧及抗阻力训练均能够有效降低甲基苯丙胺戒断者的药物渴求度。③运动对甲基苯丙胺介导的机体成瘾具有内在调控作用,首先,运动可通过影响大脑腹侧被盖区酪氨酸羟化酶的表达,进而刺激多巴胺受体偶联蛋白的表达,促进大脑奖赏区域多巴胺的合成,弥补由于甲基苯丙胺成瘾导致的多巴胺耗竭;其次,运动也可通过调控蛋白激酶A抑制剂,影响多巴胺D1受体介导的蛋白激酶A信号通路,通过抑制蛋白激酶A从而影响环磷酸腺苷反应结合蛋白,实现对甲基苯丙胺成瘾的调控;最后,运动也可在基因水平上通过影响大脑红核区细胞c-fos基因的表达,激活该区域谷氨酸神经元亚群,产生奖赏效应,实现对甲基苯丙胺成瘾的改善。④虽然目前研究已证实运动与甲基苯丙胺成瘾的关系,且已明晰运动作用的脑内机制,但是否还存在运动作用的其他脑内调控途径有待通过设计更为科学、严谨的动物或人体实验,从细胞或分子学水平出发进行深入探究。展开更多
Background:The role of neuroplasticity in epilepsy has been widely studied in experimental models and human brain samples.However,the results are contradictory and it remains unclear if neuroplasticity is more related...Background:The role of neuroplasticity in epilepsy has been widely studied in experimental models and human brain samples.However,the results are contradictory and it remains unclear if neuroplasticity is more related to the cause or the consequence of epileptic seizures.Clarifying this issue can provide insights into epilepsy therapies that target the disease mechanism and etiology rather than symptoms.Therefore,this study was aimed to investigate the dynamic changes of structural plasticity in a pilocarpine rat model of epilepsy.Methods:A single acute dose of pilocarpine(380 mg/kg,i.p.)was injected into adult male Wistar rats to induce status epilepticus(SE).Animal behavior was monitored for 2 h.Immunohistochemical staining was performed to evaluate neurogenesis in the CA3 and dentate gyrus(DG)regions of hippocampus using biomarkers Ki67 and doublecortin(DCX).The Golgi-Cox method was performed to analyze dendritic length and complexity.All experiments were performed in control rats(baseline),at 24 h after SE,on day 20 after SE(latent phase),after the first and 10th spontaneous recurrent seizures(SRS;chronic phase),and in non-epileptic rats(which did not manifest SRS 36 days after pilocarpine injection).Results:SE significantly increased the number of Ki67 and DCX-positive cells,suggesting neurogenesis during the latent phase.The dendritic complexity monitoring showed that plasticity was altered differently during epilepsy and epileptogenesis,suggesting that the two processes are completely separate at molecular and physiological levels.The numbers of spines and mushroom-type spines were increased in the latent phase.However,the dendritogenesis and spine numbers did not increase in rats that were unable to manifest spontaneous seizures after SE.Conclusion:All parameters of structural plasticity that increase during epileptogenesis,are reduced by spontaneous seizure occurrence,which suggests that the development of epilepsy involves maladaptive plastic changes.Therefore,the maladaptive plasticity biomarkers can be used to predict epilepsy before development of SRS in the cases of serious brain injury.展开更多
文摘The pathophysiology of depression has been traditionally attributed to a chemical imbalance and critical interactions between genetic and environmental risk factors, and antidepressant drugs suggested to act predominantly amplifying monoaminergic neurotransmission. This conceptualization may be currently considered reductive. The current literature about the pathophysiological mechanisms underlying depression, stress-related disorders and antidepressant treatment was examined. In order to provide a critical overview about neuroplasticity, depression and antidepressant drugs, a detailed Pubmed/Medline, Scopus, Psyc Lit, and Psyc Info search to identify all papers and book chapters during the period between 1980 and 2011 was performed. Pathological stress and depression determine relevant brain changes such as loss of dendritic spines and synapses, dendritic atrophy as well as reduction of glial cells(both in number and size) in specific areas such as the hippocampus and prefrontal cortex. An increased dendritic arborisation and synaptogenesis may instead be observed in the amygdala as a consequence of depression and stress-related disorders. While hippocampal and prefrontal functioning was impaired, amygdala functioning was abnormally amplified. Most of molecular abnormalities and biological changes of aberrant neuroplasticity may be explained by the action of glutamate. Antidepressant treatment is associated with neurogenesis, gliogenesis, dendritic arborisation, new synapse formation and cell survival both in the hippocampus and prefrontal cortex. Antidepressants(ADs) induce neuroplasticity mechanisms reversing the pathological effects of depression and stress-related disorders. The neuroplasticity hypothesis may explain the therapeutic and prophylactic action of ADs representing a new innovative approach to the pathophysiology of depression and stress-related disorders.
基金supported by grants from Edith Cowan Universitythe McCusker Alzheimer’s Research Foundationthe National Health and Medical Research Council
文摘Dear editors,Neurodegenerative diseases are now associated with the global obesity and diabetes epidemic in the developing and developed world.Neurodegenerative diseases are a heterogeneous group of disorders with complex factors such as neurohumoral,endocrine and environmental factors involved in induction of these neurodegenerative diseases.The future of science and medicine in neurodegenerative diseases is now dependent on nutritional genomics with insulin resistance a major factor in the induction of neurodegenerative diseases.Nutritional genomics now involves the anti-aging gene Sirtuin 1(Sirt 1)that is important to the prevention of insulin resistance with its critical involvement in the immune system(Martins,2018a,b).Sirt 1 inactivation leads to toxic immune reactions connected to the acceleration of neuron death in various communities.Appetite control with relevance to immunometabolism has become of critical importance to the treatment of neurodegeneration(Figure 1).Nutritional diets activate the heat shock gene Sirt 1 to prevent the increase in heat shock proteins connected to autoimmune disease,mitophagy(Martins,2018a,b)and irreversible programmed cell death in global populations(Figure 1).
文摘Depression is a common mental disorder and one of the leading causes of disability around the world.Monoaminergic antidepressants often take weeks to months to work and are not effective for all patients.This has led to a search for a better understanding of the pathogenesis of depression as well as to the development of novel antidepressants.One such novel antidepressant is ketamine,which has demonstrated both clinically promising results and contributed to new explanatory models of depression,including the potential role of neuroplasticity in depression.Early clinical trials are now showing promising results of serotonergic psychedelics for depression;however,their mechanism of action remains poorly understood.This paper seeks to review the effect of depression,classic antidepressants,ketamine,and serotonergic psychedelics on markers of neuroplasticity at a cellular,molecular,electrophysiological,functional,structural,and psychological level to explore the potential role that neuroplasticity plays in the treatment response of serotonergic psychedelics.
文摘Exploratory studies developed at several neurosciences laboratories at universities around the world show us through the experience that there is a biological process called neuroplasticity. Because of this oldest concept about the neuronal formation, scientists also thought that if a particular area of the adult brain was damaged, the nerve cells could not form new connections and the functions controlled by this field of the brain would be permanently lost or could not be regenerate. However, studies have overturned this old view, and currently, scientists recognize that the brain continues to reorganize itself by forming new neural connections during the life. This phenomenon is called neuroplasticity that refers to the potential which the brain should be reorganized by creating new neural pathways to adapt, as it needs.
文摘Neuroplasticity is a condition that is present from birth, being found in the central and peripheral nervous system, in both physiological and pathological terms. Based on the findings, therapeutic and non-therapeutic attempts were tested on spinal cord trauma to recover locomotor function below the level of the injury. The work defined and showed other forms of the term neuroplasticity, talk about some pathological and non-pathological conditions, and, finally, show neuroplasticity and some of its treatments in the spinal cord injury process. A narrative literature review from 2000 to 2020 of the PubMed platform was conducted and analysis of two books for the elaboration of this <span>work. Animal/human studies were included that addressed pathologies,</span> forms of treatment for spinal trauma, and qualis from B1 to A1. Pre-2000 articles, which addressed neuroplasticity only to understand the molecular mechanisms and articles that were not in English, were excluded. As a result, the main molecules and structures that inhibit neuroplasticity were found, and, based on their knowledge, forms of treatments were developed to inhibit these molecules and structures to assist in neuroplasticity and assist in possible functional recovery. It can be concluded that the physiological barriers are already being overcome by the most recent forms of treatment and that soon new studies may propose a form of treatment that is protocoled for all patients.
基金the Spastic Paraplegia Foundation(SPF)Professor Peter Bede and the Computational Neuroimaging Group are also the Health Research Board(HRB EIA-2017-019)+3 种基金the Irish Institute of Clinical Neuroscience(IICN)the EU Joint Programme-Neurodegenerative Disease Research(JPND)the Andrew Lydon scholarshipthe Iris O'Brien Foundation。
文摘Amyotrophic lateral sclerosis is a relentlessly progressive multi-system condition.The clinical picture is dominated by upper and lower motor neuron degeneration,but extra-motor pathology is increasingly recognized,including cerebellar pathology.Post-mortem and neuroimaging studies primarily focus on the chara cterization of supratentorial disease,des pite emerging evidence of cerebellar degeneration in amyotrophic lateral sclerosis.Cardinal clinical features of amyotrophic lateral sclerosis,such as dysarthria,dysphagia,cognitive and behavioral deficits,saccade abnormalities,gait impairment,respiratory weakness and pseudobulbar affect are likely to be exacerbated by co-existing cerebellar pathology.This review summarizes in vivo and post mortem evidence for cerebellar degeneration in amyotrophic lateral scle rosis.Structural imaging studies consistently capture cerebellar grey matter volume reductions,diffusivity studies readily detect both intra-cerebellar and cerebellar peduncle white matter alte rations and functional imaging studies commonly report increased functional connectivity with supratentorial regions.Increased functional connectivity is commonly interpreted as evidence of neuro plasticity representing compensatory processes despite the lack of post-mortem validation.There is a scarcity of post-mortem studies focusing on cerebellar alte rations,but these detect pTDP-43 in cerebellar nuclei.Ce rebellar pathology is an overloo ked facet of neurodegeneration in amyotrophic lateral sclerosis despite its contribution to a multitude of clinical symptoms,wides p read connectivity to spinal and supratentorial regions and putative role in compensating for the degeneration of primary motor regions.
文摘The rehabilitation of musculoskeletal dysfunctions(MSD)such as osteoarthritis,anterior cruciate ligament injuries and low back pain focuses on symptomatic management of pain followed by stretching and strengthening.However,these interventions focus just on symptomatic pain management and addressing musculoskeletal impairments.But it has been found that neuroplastic changes continue to occur throughout these pathologies and sometimes even are persistent,as conventional rehabilitation doesn’t focus on these changes therefore chances of reinjury increase.Therefore this article discusses underlying neuroplastic changes associated with MSD and neuroplasticity-based interventions for better clinical outcomes.
基金supported by the FWF Special Research Program(SFB)F44(F4413-B23)"Cell Signaling in Chronic CNS Disorders",and through funding from the European Union’s Seventh Framework Program(FP7/2007-2013)under grant agreements n°HEALTH-F2-2011-278850(INMi ND),n°HEALTH-F2-2011-279288(IDEA),n°FP7-REGPOT-316120(Glow Brain)a startup grant from the Faculty Recharge Programme,University Grants Commission(UGC-FRP),New Delhi,India(to MK)+1 种基金a research grant from DST-SERB,New Delhi,India(EEQ/2016/000639)(to MK)an Early Career Research Award(ECR/2016/000741)(to MK)
文摘The brain is a dynamic organ of the biological renaissance due to the existence of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity in the intact brain and contributes to neural regeneration in response to brain diseases and injury. The occurrence of adult neurogenesis has unequivocally been witnessed in human subjects, experimental and wildlife research including rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in which generation of neuroblasts namely, neuroblastosis appears to be an integral process that occur in the limbic system and basal ganglia in addition to the canonical neurogenic niches. Neuroblastosis can be regulated by various factors and contributes to different functions of the brain. The characteristics and fate of neuroblasts have been found to be different among mammals regardless of their cognitive functions. Recently, regulation of neuroblastosis has been proposed for the sensorimotor interface and regenerative neuroplasticity of the adult brain. Hence, the understanding of adult neurogenesis at the functional level of neuroblasts requires a great scientific attention. Therefore, this mini-review provides a glimpse into the conceptual development of neuroplasticity, discusses the possible role of different types of neuroblasts and signifies neuroregenerative failure as a potential cause of dementia.
基金supported by a grant from the National Natural Science Foundation of China,No.30873390
文摘Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cognitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.
基金supported by the National Natural Science Foundation of China,No.30973165,81372108a grant from Clinical Research 5010 Program Mission Statement of Sun Yat-Sen University,China,No.2014001
文摘Gait disorders drastically affect the quality of life of stroke survivors,making post-stroke rehabilitation an important research focus.Noninvasive brain stimulation has potential in facilitating neuroplasticity and improving post-stroke gait impairment.However,a large inter-individual variability in the response to noninvasive brain stimulation interventions has been increasingly recognized.We first review the neurophysiology of human gait and post-stroke neuroplasticity for gait recovery,and then discuss how noninvasive brain stimulation techniques could be utilized to enhance gait recovery.While post-stroke neuroplasticity for gait recovery is characterized by use-dependent plasticity,it evolves over time,is idiosyncratic,and may develop maladaptive elements.Furthermore,noninvasive brain stimulation has limited reach capability and is facilitative-only in nature.Therefore,we recommend that noninvasive brain stimulation be used adjunctively with rehabilitation training and other concurrent neuroplasticity facilitation techniques.Additionally,when noninvasive brain stimulation is applied for the rehabilitation of gait impairment in stroke survivors,stimulation montages should be customized according to the specific types of neuroplasticity found in each individual.This could be done using multiple mapping techniques.
文摘In multiple sclerosis,only immunomodulato ry and immunosuppressive drugs are recognized as disease-modifying therapies.Howeve r,in recent years,several data from pre-clinical and clinical studies suggested a possible role of physical exe rcise as disease-modifying therapy in multiple sclerosis.Current evidence is sparse and often conflicting,and the mechanisms underlying the neuroprotective and antinflammatory role of exercise in multiple sclerosis have not been fully elucidated.Data,mainly derived from pre-clinical studies,suggest that exe rcise could enhance longterm potentiation and thus neuroplasticity,could reduce neuroinflammation and synaptopathy,and dampen astrogliosis and microgliosis.In humans,most trials focused on direct clinical and MRI outcomes,as investigating synaptic,neuroinflammato ry,and pathological changes is not straightfo rward compared to animal models.The present review analyzed current evidence and limitations in research concerning the potential disease-modifying therapy effects of exercise in multiple sclerosis in animal models and human studies.
基金supported by Notional Institutes of Health Grant,No.1R01NS100710-01A1(to YX)。
文摘Traumatic brain injury is a serious and complex neurological condition that affects millions of people worldwide.Despite significant advancements in the field of medicine,effective treatments for traumatic brain injury remain limited.Recently,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain injury.Extracellular vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and microRNAs.When administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional outcomes.In preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor recovery.While further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain injury.In this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.
基金supported by the Natural Science Foundation of Hubei Province,No.2022CBF680Independent Scientific Research Project of Wuhan University,No.2042022kf1119(both to LD)。
文摘Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of life.Many stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic impact.Currently,poststroke brain dysfunction is a major and difficult area of treatment.Vagus nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s disease.It is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro ns.In animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and neurogenesis.At present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve stimulation.Clinical studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke patients.Further clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same effect.In this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic stroke.We go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve stimulation.Finally,we provide a more comprehensive evaluation of the advantages and disadvantages of different types of vagus nerve stimulation in the treatment of cerebral ischemia and provide an outlook on the developmental trends.We believe that vagus nerve stimulation,as an effective treatment for stroke,will be widely used in clinical practice to promote the recovery of stroke patients and reduce the incidence of disability.
文摘BACKGROUND Anosmia was one of the main symptoms of coronavirus disease 2019(COVID-19).A psychiatric history(i.e.,depression)may be an independent contributor to the risk of COVID-19 diagnosis,and COVID-19 survivors appear to have an increased risk of neuropsychiatric sequelae(bidirectional association).AIM To compare the rate of psychiatric disorder among post-COVID patients without anosmia vs patients with persistent olfactory complaints.METHODS We conducted a prospective case control study from March 2020 to May 2021.Patients recruited at the ENT department of Nice University Hospital had a subjective olfactory complaint(visual analogue scale)for over 6 wk and a molecular or CT-proven severe acute respiratory syndrome coronavirus 2 diagnosis confirmed by serology.Post-COVID patients without persistent olfactory disorders were recruited at the university hospital infectiology department.Psychiatric medical histories were collected by a psychiatrist during the assessments.RESULTS Thirty-four patients with post-COVID-19 olfactory complaints were included in the first group of the study.Fifty percent of the patients were female(n=17).The group’s mean age was 40.5±12.9 years.The control group included 32 participants,of which 34.4%were female(n=11),and had a mean age of 61.2±12.2 years.The rate of psychiatric disorder among post-COVID patients with olfactory complaints was significatively higher(41.7%)than among patients without(18.8%)(χ2=5.9,P=0.015).CONCLUSION The presence of a psychiatric history may constitute a potential risk factor for the development of long COVID due to persistent anosmia.It therefore seems important to establish reinforced health monitoring after a COVID 19 infection in at-risk patients.Further prospective,translational,and collaborative studies are needed to extrapolate these results to the general population.
文摘背景:抑制控制和药物渴求是评估甲基苯丙胺成瘾者药物戒断的核心要素,备受学界关注。众所周知,要彻底实现对药物成瘾的戒断,恢复吸毒者受损的抑制控制功能,有效降低对药物的渴求是关键。目的:旨在通过系统分析运动与甲基苯丙胺戒断者抑制控制和药物渴求的关系,找出促进甲基苯丙胺成瘾戒断的有效运动干预方案,并进一步探究运动作用的内在机制,以期为未来运动运用于毒品戒断提供理论上的支持和应用上的参考。方法:通过检索中国知网、万方、维普、Web of Science及PubMed数据库,中文检索词为“运动,体育锻炼,甲基苯丙胺,抑制功能,渴求度,成瘾”等,英文检索词为“Sport*,Exercise,Methamphetamine,Drug craving,Executive function,Addiction”等,依据纳入和排除标准对文献进行筛选,最终获得目标文献65篇进行综述分析。结果与结论:①运动对甲基苯丙胺戒断者抑制控制方面,急性和长期中等强度有氧运动或急性中高强度间歇训练均能够显著提升甲基苯丙胺戒断者抑制控制能力,对于长期有氧运动而言,有氧操课练习或全身性的综合练习效果更佳,若运动形式为功率自行车,建议增加运动干预频次。②运动对甲基苯丙戒断者药物渴求度方面,急性中等强度有氧运动和抗阻力训练或长期中等强度、高强度或递增负荷的有氧及抗阻力训练均能够有效降低甲基苯丙胺戒断者的药物渴求度。③运动对甲基苯丙胺介导的机体成瘾具有内在调控作用,首先,运动可通过影响大脑腹侧被盖区酪氨酸羟化酶的表达,进而刺激多巴胺受体偶联蛋白的表达,促进大脑奖赏区域多巴胺的合成,弥补由于甲基苯丙胺成瘾导致的多巴胺耗竭;其次,运动也可通过调控蛋白激酶A抑制剂,影响多巴胺D1受体介导的蛋白激酶A信号通路,通过抑制蛋白激酶A从而影响环磷酸腺苷反应结合蛋白,实现对甲基苯丙胺成瘾的调控;最后,运动也可在基因水平上通过影响大脑红核区细胞c-fos基因的表达,激活该区域谷氨酸神经元亚群,产生奖赏效应,实现对甲基苯丙胺成瘾的改善。④虽然目前研究已证实运动与甲基苯丙胺成瘾的关系,且已明晰运动作用的脑内机制,但是否还存在运动作用的其他脑内调控途径有待通过设计更为科学、严谨的动物或人体实验,从细胞或分子学水平出发进行深入探究。
文摘Background:The role of neuroplasticity in epilepsy has been widely studied in experimental models and human brain samples.However,the results are contradictory and it remains unclear if neuroplasticity is more related to the cause or the consequence of epileptic seizures.Clarifying this issue can provide insights into epilepsy therapies that target the disease mechanism and etiology rather than symptoms.Therefore,this study was aimed to investigate the dynamic changes of structural plasticity in a pilocarpine rat model of epilepsy.Methods:A single acute dose of pilocarpine(380 mg/kg,i.p.)was injected into adult male Wistar rats to induce status epilepticus(SE).Animal behavior was monitored for 2 h.Immunohistochemical staining was performed to evaluate neurogenesis in the CA3 and dentate gyrus(DG)regions of hippocampus using biomarkers Ki67 and doublecortin(DCX).The Golgi-Cox method was performed to analyze dendritic length and complexity.All experiments were performed in control rats(baseline),at 24 h after SE,on day 20 after SE(latent phase),after the first and 10th spontaneous recurrent seizures(SRS;chronic phase),and in non-epileptic rats(which did not manifest SRS 36 days after pilocarpine injection).Results:SE significantly increased the number of Ki67 and DCX-positive cells,suggesting neurogenesis during the latent phase.The dendritic complexity monitoring showed that plasticity was altered differently during epilepsy and epileptogenesis,suggesting that the two processes are completely separate at molecular and physiological levels.The numbers of spines and mushroom-type spines were increased in the latent phase.However,the dendritogenesis and spine numbers did not increase in rats that were unable to manifest spontaneous seizures after SE.Conclusion:All parameters of structural plasticity that increase during epileptogenesis,are reduced by spontaneous seizure occurrence,which suggests that the development of epilepsy involves maladaptive plastic changes.Therefore,the maladaptive plasticity biomarkers can be used to predict epilepsy before development of SRS in the cases of serious brain injury.
