Brain asymmetry for processing visual information is widespread in animals.However,it is still unknown how the complexity of the underlying neural network activities represents this asymmetrical pattern in the brain.I...Brain asymmetry for processing visual information is widespread in animals.However,it is still unknown how the complexity of the underlying neural network activities represents this asymmetrical pattern in the brain.In the present study,we investigated this complexity using the approximate entropy(ApEn)protocol for electroencephalogram(EEG)recordings from the forebrain and midbrain while the music frogs(Nidirana daunchina)attacked prey stimulus.The results showed that(1)more significant prey responses were evoked by the prey stimulus presented in the right visual field than that in the left visual field,consistent with the idea that right-eye preferences for predatory behaviors exist in animals including anurans;(2)in general,the ApEn value of the left hemisphere(especially the left mesencephalon)was greatest under various stimulus conditions,suggesting that visual lateralization could be reflected by the dynamics of underlying neural network activities and that the stable left-hemisphere dominance of EEG ApEn may play an important role in maintaining this brain asymmetry.展开更多
BACKGROUND: Previous studies have analyzed cerebral activation and lateralization of cognitive functions, as well as cerebellar function with reference to high-level cognitive processing. However, there has been very...BACKGROUND: Previous studies have analyzed cerebral activation and lateralization of cognitive functions, as well as cerebellar function with reference to high-level cognitive processing. However, there has been very little research on systematization and diversification. In particular, there are no reports on cerebellar lateralization, although reliable results have been reported on cerebral lateralization. OBJECTIVE: This study analyzed cerebellar activation and lateralization in relation to verbal and visuospatial tasks using functional magnetic resonance imaging (fMRI). DESIGN, TIME AND SETTING: A block design for fMRI observation was performed at the fMRI Laboratory, Brain Science Research Center, Korea Advanced Institute of Science and Technology from May 2006 to September 2008. PARTICIPANTS: Sixteen healthy, male, college students, aged (23.3 ± 0.5) years, and 16 healthy, male, college students, aged (21.5 ± 2.3) years, participated in the study, respectively. METHODS: Verbal and visuospatial tasks were presented while functional brain images were acquired using a 3T fMRI system. Verbal analogy testing required the subject to select the word with the same relationship as one of the given words. Verbal antonym testing required the subject to select the word with a different meaning among four words. Visuospatial tasks involved selecting a shape that corresponded to a given figure with four examples, as well as selecting a development figure of a diagram. MAIN OUTCOME MEASURES: Changes in cerebellar activation and lateralization between two cognition tasks. RESULTS: Bilateral hemisphere Iobules VI and IX, right hemisphere Iobule VIII, bilateral hemisphere Iobules Crus I, and vermis Iobule IV, V, and Vl were closely related to verbal tasks in comparison to visuospatial tasks. Conversely, bilateral hemisphere Iobules IV and V, as well as the right hemisphere Iobule VI, were closely related to visuospatial tasks compared to verbal tasks. There was no great difference between the number of activated voxels in the cerebellums during the tasks, and cerebellar lateralization was not observed. CONCLUSION: In the cerebellum, the activation region, but not lateralization, was different between verbal and visuospatial tasks.展开更多
Brain lateralization for language in high-functioning children with autism spectrum conditions (ASC) and sensory processing were explored as a part of a neuropsychological profile. A dichotic listening test and the Lu...Brain lateralization for language in high-functioning children with autism spectrum conditions (ASC) and sensory processing were explored as a part of a neuropsychological profile. A dichotic listening test and the Luria laterality subtest were administered to all participants (including controls) and the sensory profile test only to the ASC group. The usual right ear advantage was not exhibited by children with ASC and anomalies in auditory filtering were found. The sensory profile of 60% of the sample was characterized by hypersensitivity to auditory stimuli, hyposensitivity to vestibular information, high emotional reactions to sensory experiences, poor psychosocial coping strategies, high distractibility and inability to interpret body and facial language. Hyper-responsiveness to environmental auditory stimuli was significantly associated with impaired attention. Similarly, non-adaptive responses to sensory quotidian experiences were strongly connected to poor coping strategies. Our results, although preliminary, contribute to emphasizing the importance of including additional assessment methods such as the dichotic listening and the sensory profile questionnaire in the evaluation of cognitive profile in high-functioning children with ASC to plan an individualized psycho-educative intervention.展开更多
The objective is to study changes in EEG time-domain Kolmogorov entropy and cortical lateralization of brain function areas during complex problem solving mental task in healthy human subjects. EEG data for healthy su...The objective is to study changes in EEG time-domain Kolmogorov entropy and cortical lateralization of brain function areas during complex problem solving mental task in healthy human subjects. EEG data for healthy subjects are acquired during complex problem solving mental task using a net of 6 electrodes. The subject was given a nontrivial multiplication problem to solve and the signals were recorded for 10s during the task. Kolmogorov entropy values during the task were calculated. It was found that Kolmogorov entropy values were obviously greater in P4 channel (right) than ones in P3 channel (left) during complex problem solving task. It indicated that all subjects presented significant left parietal lateralization for the total frequency spectrum. These results suggest that it may be possible to noninvasively lateralize, and even eventually localize, cerebral regions essential for particular mental tasks from scalp EEG data.展开更多
In recent decades, functional magnetic resonance imaging (fMRI) has proven to be more effective than the Wada test in the evaluation of language lateralization in special populations such as epileptic patients and chi...In recent decades, functional magnetic resonance imaging (fMRI) has proven to be more effective than the Wada test in the evaluation of language lateralization in special populations such as epileptic patients and children. However, fMRI requires that subjects remain motionless during data acquisition, making the assessment of receptive and expressive language difficult in young children and population with special needs. Near-Infrared spectroscopy (NIRS) is a non- invasive technique that has proven to be more tolerant to motion artifacts. The aim of the present study was to investigate the use of NIRS to assess receptive language patterns using a story listening paradigm. Four native French-speakers listened to stories read aloud by a bilingual speaker in both French and Arabic. To determine if the signal recorded was affected by episodic memory processes, a familiar story and an unknown story were presented. Results showed that listening to stories in French elicited a significantly higher left lateralized response than listening to stories in Arabic, independently of the familiarity of the story. These results confirm that NIRS is a useful non-invasive technique to assess receptive language in adults and can be used to investigate language lateralization among children and epileptic patients slated for epilepsy surgery.展开更多
This study investigated the effect of transcranial direct current stimulation(t DCS) polarity depending on lateralized function of task property in normal individuals performing visuomotor and simple repetitive task...This study investigated the effect of transcranial direct current stimulation(t DCS) polarity depending on lateralized function of task property in normal individuals performing visuomotor and simple repetitive tasks. Thirty healthy participants with no neurological disorders were recruited to participate in this study. Participants were randomly allocated into active or control condition. For the active condition, t DCS intensity was 2 m A with stimulation applied for 15 minutes to the right hemisphere(t DCS condition). For the sham control, electrodes were placed in the same position, but the stimulator was turned off after 30 seconds(sham condition). The tapping and tracking task tests were performed before and after for both conditions. Univariate analysis revealed significant difference only in the tracking task. For direct comparison of both tasks within each group, the tracking task had significantly higher Z score than the tapping task in the t DCS group(P 〈 0.05). Thus, our study indicates that stimulation of the right hemisphere using t DCS can effectively improve visuomotor(tracking) task over simple repetitive(tapping) task.展开更多
This paper reviews research on hemispheric lateralization.There are neurological evidences for the lateralization of speech and language functions and inter-and intrahemispherical differences between males and females...This paper reviews research on hemispheric lateralization.There are neurological evidences for the lateralization of speech and language functions and inter-and intrahemispherical differences between males and females.The results for the study of lateralization and bilingualism are mixed,proving the complexity and multidimensionality of lateralization.展开更多
Asymmetries in bilateral organisms attract a lot of curiosity given that they are conspicuous departures from the norm.They allow the investigation of the integration at different levels of biological organization.Her...Asymmetries in bilateral organisms attract a lot of curiosity given that they are conspicuous departures from the norm.They allow the investigation of the integration at different levels of biological organization.Here we study whether and how behavioral and asymmetrical anatomical traits coevolved and work together.We ask if asymmetry is determined locally for each trait or at a whole individual level in a species bearing conspicuous asymmetrical genitalia.Asymmetric genitalia evolved in many species;however,in most cases the direction of asymmetry is fixed.Therefore,it has been rarely determined if there is an association between the direction of asymmetry in genitalia and other traits.In onesided livebearer fish of the genus Jenynsia(Cyprinodontiformes,Anablepidae),the anal fin of males is modified into a gonopodium,an intromittent organ that serves to inseminate females.The gonopodium shows a conspicuous asymmetry,with its tip bending either to the left or the right.By surveying 13 natural populations of Jenynsia lineata,we found that both genital morphs are equally common in wild populations.In a series of experiments in a laboratory population,we discovered asymmetry and lateralization for multiple other traits;yet,the degree of integration varied highly among them.Lateralization in exploratory behavior in response to different stimuli was not associated with genital morphology.Interestingly,the direction of genital asymmetry was positively correlated with sidedness of mating preference and the number of neuromasts in the lateral line.This suggests integration of functionally linked asymmetric traits;however,there is no evidence that asymmetry is determined at the whole individual level in our study species.展开更多
The work is to explore the relationship between the levels of cytokines(IL-1β and IL-6)in C57BL/6J mice treated with MPTP and brain lateralization.By using paw preference test,right-pawed,left-pawed mice models were ...The work is to explore the relationship between the levels of cytokines(IL-1β and IL-6)in C57BL/6J mice treated with MPTP and brain lateralization.By using paw preference test,right-pawed,left-pawed mice models were established.Following single injection of 1-methyl-4-phenyl-2,3,6-tetrahydropyrid(MPTP)(40 mg/kg)to impair dopaminergic neuron,enzyme linked immunosorbent assay(ELISA)kits were used for detection of plasma levels of cytokines.The results showed that in saline treated C57BL/6J mice(control),there was no obvious difference observed between left-pawed and right-pawed mice in plasma levels of IL-1β and IL-6.In MPTP treated mice,there was no difference between level of IL-1β in left-pawed mice and that in right-pawed ones in statistics,that is,they were increased on day 1 and day 3,but decreased on day 6.The plasma level of IL-6 was lower in left-pawed than that in right-pawed mice (p<0.005)after MPTP treatment. On day 1 and day 3,the level of IL-6 was almost the same as control;on day 6,it was significantly increased, higher than that of control(p<0.001)in left-pawed mice.While in right-pawed mice,on day 1 and day 3,it was no different from control,too.And on day 6,it significantly increased in compared with control(p<0.005).In conclusion,the level of plasma IL-6 of C57BL/6J mice treated with MPTP increased.The variation of IL-6 was correlated to brain lateralization.Cellular & Molecular Immunology.2004;1(3):219-223.展开更多
Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann c...Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.展开更多
Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is...Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.展开更多
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d...Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.展开更多
Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understan...Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.展开更多
Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–b...Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.展开更多
Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these...Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.展开更多
Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves ...Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.展开更多
The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.展开更多
Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives ...Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.展开更多
Functional asymmetries, for example, the preferential involvement of 1 brain hemisphere to process stimuli, may increase brain efficiency and the capacity to carry out tasks simultaneously. We investigated which hemis...Functional asymmetries, for example, the preferential involvement of 1 brain hemisphere to process stimuli, may increase brain efficiency and the capacity to carry out tasks simultaneously. We investigated which hemisphere was primarily invoIved in processing acoustic stimuli in goats using a headorienting paradigm. Three playbacks using goat vocalizations recorded in different contexts: food anticipation (positive), isolation (negative), food frustration (negative), as well as 1 playback involving dog barks (negative) were presented on the left and right sides of the test subjects simultaneously. The head-orienting response (left or right) and latency to resume feeding were recorded. The direction of the head-orienting response did not differ between the various playbacks. However, when the head-orienting response was tested against chanee level, goats showed a right bias regardless of the stimuli presented. Goats responded more to dog barks than to food frustration calls, whereas responses to food anticipation and isolation calls were intermediate. In addition, the latency to resume feeding, an indicator of fear reaction, was not affected by the kind of vocalization presented. These results provide evidence for asymmetries in goat vocal perceptio n of emotional-li nked con specific and heterospecific calls. They also suggest involvement of the left brain hemisphere for processing acoustic stimuli, which might have been perceived as familiar and non -threate ning.展开更多
Behavioural lateralization,which reflects the functional specializations of the two brain hemispheres,is assumed to play an important role in cooperative intraspecific interactions.However,there are few studies focuse...Behavioural lateralization,which reflects the functional specializations of the two brain hemispheres,is assumed to play an important role in cooperative intraspecific interactions.However,there are few studies focused on the lateralization in cooperative behaviours of individuals,especially in a natural setting.In the present study,we investigated Iateralized spatial interactions between the partners in life-long monogamous pairs.The male-female pairs of two geese species(barnacle,Branta leucopsis,and white-fronted,Anser albifrons geese),were observed during different stages of the annual cycle in a variety of conditions.In geese flocks,we recorded which visual hemifield(left/right)the following partner used to monitor the leading partner relevant to the type of behaviour and the disturbance factors.In a significant majority of pairs,the following bird viewed the leading partner with the left eye during routine behaviours such as resting and feeding in undisturbed conditions.This behavioural lateralization,implicating the right hemisphere processing,was consistent across the different aggregation sites and years of the study.In contrast,no significant bias was found in a variety of geese behaviours associated with enhanced disturbance(when alert on water,flying or fleeing away when disturbed,feeding during the hunting period,in urban area feeding and during moulting).We hypothesize that the increased demands for right hemisphere processing to deal with stressful and emergency situations may interfere with the manifestation of lateralization in social interactions.展开更多
基金supported by the grants from the National Natural Science Foundation of China(No.31970422,No.31672305 and No.31372217 to Guangzhan Fang)the Key Research Project of Education Department of Sichuan Province(No.18ZA0321 to Yansu Liu)。
文摘Brain asymmetry for processing visual information is widespread in animals.However,it is still unknown how the complexity of the underlying neural network activities represents this asymmetrical pattern in the brain.In the present study,we investigated this complexity using the approximate entropy(ApEn)protocol for electroencephalogram(EEG)recordings from the forebrain and midbrain while the music frogs(Nidirana daunchina)attacked prey stimulus.The results showed that(1)more significant prey responses were evoked by the prey stimulus presented in the right visual field than that in the left visual field,consistent with the idea that right-eye preferences for predatory behaviors exist in animals including anurans;(2)in general,the ApEn value of the left hemisphere(especially the left mesencephalon)was greatest under various stimulus conditions,suggesting that visual lateralization could be reflected by the dynamics of underlying neural network activities and that the stable left-hemisphere dominance of EEG ApEn may play an important role in maintaining this brain asymmetry.
文摘BACKGROUND: Previous studies have analyzed cerebral activation and lateralization of cognitive functions, as well as cerebellar function with reference to high-level cognitive processing. However, there has been very little research on systematization and diversification. In particular, there are no reports on cerebellar lateralization, although reliable results have been reported on cerebral lateralization. OBJECTIVE: This study analyzed cerebellar activation and lateralization in relation to verbal and visuospatial tasks using functional magnetic resonance imaging (fMRI). DESIGN, TIME AND SETTING: A block design for fMRI observation was performed at the fMRI Laboratory, Brain Science Research Center, Korea Advanced Institute of Science and Technology from May 2006 to September 2008. PARTICIPANTS: Sixteen healthy, male, college students, aged (23.3 ± 0.5) years, and 16 healthy, male, college students, aged (21.5 ± 2.3) years, participated in the study, respectively. METHODS: Verbal and visuospatial tasks were presented while functional brain images were acquired using a 3T fMRI system. Verbal analogy testing required the subject to select the word with the same relationship as one of the given words. Verbal antonym testing required the subject to select the word with a different meaning among four words. Visuospatial tasks involved selecting a shape that corresponded to a given figure with four examples, as well as selecting a development figure of a diagram. MAIN OUTCOME MEASURES: Changes in cerebellar activation and lateralization between two cognition tasks. RESULTS: Bilateral hemisphere Iobules VI and IX, right hemisphere Iobule VIII, bilateral hemisphere Iobules Crus I, and vermis Iobule IV, V, and Vl were closely related to verbal tasks in comparison to visuospatial tasks. Conversely, bilateral hemisphere Iobules IV and V, as well as the right hemisphere Iobule VI, were closely related to visuospatial tasks compared to verbal tasks. There was no great difference between the number of activated voxels in the cerebellums during the tasks, and cerebellar lateralization was not observed. CONCLUSION: In the cerebellum, the activation region, but not lateralization, was different between verbal and visuospatial tasks.
文摘Brain lateralization for language in high-functioning children with autism spectrum conditions (ASC) and sensory processing were explored as a part of a neuropsychological profile. A dichotic listening test and the Luria laterality subtest were administered to all participants (including controls) and the sensory profile test only to the ASC group. The usual right ear advantage was not exhibited by children with ASC and anomalies in auditory filtering were found. The sensory profile of 60% of the sample was characterized by hypersensitivity to auditory stimuli, hyposensitivity to vestibular information, high emotional reactions to sensory experiences, poor psychosocial coping strategies, high distractibility and inability to interpret body and facial language. Hyper-responsiveness to environmental auditory stimuli was significantly associated with impaired attention. Similarly, non-adaptive responses to sensory quotidian experiences were strongly connected to poor coping strategies. Our results, although preliminary, contribute to emphasizing the importance of including additional assessment methods such as the dichotic listening and the sensory profile questionnaire in the evaluation of cognitive profile in high-functioning children with ASC to plan an individualized psycho-educative intervention.
文摘The objective is to study changes in EEG time-domain Kolmogorov entropy and cortical lateralization of brain function areas during complex problem solving mental task in healthy human subjects. EEG data for healthy subjects are acquired during complex problem solving mental task using a net of 6 electrodes. The subject was given a nontrivial multiplication problem to solve and the signals were recorded for 10s during the task. Kolmogorov entropy values during the task were calculated. It was found that Kolmogorov entropy values were obviously greater in P4 channel (right) than ones in P3 channel (left) during complex problem solving task. It indicated that all subjects presented significant left parietal lateralization for the total frequency spectrum. These results suggest that it may be possible to noninvasively lateralize, and even eventually localize, cerebral regions essential for particular mental tasks from scalp EEG data.
文摘In recent decades, functional magnetic resonance imaging (fMRI) has proven to be more effective than the Wada test in the evaluation of language lateralization in special populations such as epileptic patients and children. However, fMRI requires that subjects remain motionless during data acquisition, making the assessment of receptive and expressive language difficult in young children and population with special needs. Near-Infrared spectroscopy (NIRS) is a non- invasive technique that has proven to be more tolerant to motion artifacts. The aim of the present study was to investigate the use of NIRS to assess receptive language patterns using a story listening paradigm. Four native French-speakers listened to stories read aloud by a bilingual speaker in both French and Arabic. To determine if the signal recorded was affected by episodic memory processes, a familiar story and an unknown story were presented. Results showed that listening to stories in French elicited a significantly higher left lateralized response than listening to stories in Arabic, independently of the familiarity of the story. These results confirm that NIRS is a useful non-invasive technique to assess receptive language in adults and can be used to investigate language lateralization among children and epileptic patients slated for epilepsy surgery.
文摘This study investigated the effect of transcranial direct current stimulation(t DCS) polarity depending on lateralized function of task property in normal individuals performing visuomotor and simple repetitive tasks. Thirty healthy participants with no neurological disorders were recruited to participate in this study. Participants were randomly allocated into active or control condition. For the active condition, t DCS intensity was 2 m A with stimulation applied for 15 minutes to the right hemisphere(t DCS condition). For the sham control, electrodes were placed in the same position, but the stimulator was turned off after 30 seconds(sham condition). The tapping and tracking task tests were performed before and after for both conditions. Univariate analysis revealed significant difference only in the tracking task. For direct comparison of both tasks within each group, the tracking task had significantly higher Z score than the tapping task in the t DCS group(P 〈 0.05). Thus, our study indicates that stimulation of the right hemisphere using t DCS can effectively improve visuomotor(tracking) task over simple repetitive(tapping) task.
文摘This paper reviews research on hemispheric lateralization.There are neurological evidences for the lateralization of speech and language functions and inter-and intrahemispherical differences between males and females.The results for the study of lateralization and bilingualism are mixed,proving the complexity and multidimensionality of lateralization.
基金This work was supported by the Deutsche Forschungsgemeinschaft,Grant Number TO914/2-1 to J.T-D.
文摘Asymmetries in bilateral organisms attract a lot of curiosity given that they are conspicuous departures from the norm.They allow the investigation of the integration at different levels of biological organization.Here we study whether and how behavioral and asymmetrical anatomical traits coevolved and work together.We ask if asymmetry is determined locally for each trait or at a whole individual level in a species bearing conspicuous asymmetrical genitalia.Asymmetric genitalia evolved in many species;however,in most cases the direction of asymmetry is fixed.Therefore,it has been rarely determined if there is an association between the direction of asymmetry in genitalia and other traits.In onesided livebearer fish of the genus Jenynsia(Cyprinodontiformes,Anablepidae),the anal fin of males is modified into a gonopodium,an intromittent organ that serves to inseminate females.The gonopodium shows a conspicuous asymmetry,with its tip bending either to the left or the right.By surveying 13 natural populations of Jenynsia lineata,we found that both genital morphs are equally common in wild populations.In a series of experiments in a laboratory population,we discovered asymmetry and lateralization for multiple other traits;yet,the degree of integration varied highly among them.Lateralization in exploratory behavior in response to different stimuli was not associated with genital morphology.Interestingly,the direction of genital asymmetry was positively correlated with sidedness of mating preference and the number of neuromasts in the lateral line.This suggests integration of functionally linked asymmetric traits;however,there is no evidence that asymmetry is determined at the whole individual level in our study species.
基金supported by INSERM.Shantou University and A French-Chinese Agreement(PRA B97-03 from the Association France-Chinese Pour-La Recherche Scientifique&Technique)the National Natural Science Foundation of China(#302712l1.#30371315)the Scientific and Developing Foundation of Shantou University(L0001l).
文摘The work is to explore the relationship between the levels of cytokines(IL-1β and IL-6)in C57BL/6J mice treated with MPTP and brain lateralization.By using paw preference test,right-pawed,left-pawed mice models were established.Following single injection of 1-methyl-4-phenyl-2,3,6-tetrahydropyrid(MPTP)(40 mg/kg)to impair dopaminergic neuron,enzyme linked immunosorbent assay(ELISA)kits were used for detection of plasma levels of cytokines.The results showed that in saline treated C57BL/6J mice(control),there was no obvious difference observed between left-pawed and right-pawed mice in plasma levels of IL-1β and IL-6.In MPTP treated mice,there was no difference between level of IL-1β in left-pawed mice and that in right-pawed ones in statistics,that is,they were increased on day 1 and day 3,but decreased on day 6.The plasma level of IL-6 was lower in left-pawed than that in right-pawed mice (p<0.005)after MPTP treatment. On day 1 and day 3,the level of IL-6 was almost the same as control;on day 6,it was significantly increased, higher than that of control(p<0.001)in left-pawed mice.While in right-pawed mice,on day 1 and day 3,it was no different from control,too.And on day 6,it significantly increased in compared with control(p<0.005).In conclusion,the level of plasma IL-6 of C57BL/6J mice treated with MPTP increased.The variation of IL-6 was correlated to brain lateralization.Cellular & Molecular Immunology.2004;1(3):219-223.
基金support from the Miami Project to Cure Paralysis,the Buoniconti Fund,and the Interdisciplinary Stem Cell Institute(to AK,WDD,JDG,and ADL)the unconditional support of Dean Henri Ford of the Leonard M.Miller School of Medicine at the University of Miami.
文摘Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular junction.In amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be impaired.Recently,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such treatment.An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis.After initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and taurursodiol.The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function.We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in vitro.After a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline.None of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or changes in vital signs.Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend.A more sensitive in-house assay suggested possible inflammasome activation during the disease course.A trend for clinical stabilization was observed during the infusion period.Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles.Initial findings suggest that this approach is safe.
基金supported by the Notional Natural Science Foundation of Chino,No.82160690Colloborotive Innovation Center of Chinese Ministry of Education,No.2020-39Science and Technology Foundation of Guizhou Province,No.ZK[2021]-014(all to FZ)。
文摘Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of concentrations.Copper homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and COX17.Disruptions in copper homeostasis can lead to either the deficiency or accumulation of copper in brain tissue.Emerging evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative disorders.However,the exact mechanisms underlying these processes are not known.Copper is a potent oxidant that increases reactive oxygen species production and promotes oxidative stress.Elevated reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial dysfunction.Reactive oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory pathways.Additionally,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell death.This study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease pathogenesis.By synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of hereditary and neuronal disorders,such as Wilson's disease,Menkes'disease,Alzheimer's disease,Parkinson's disease,amyotrophic lateral sclerosis,Huntington's disease,and multiple sclerosis.Potential clinically significant therapeutic targets,including superoxide dismutase 1,D-penicillamine,and 5,7-dichloro-2-[(dimethylamino)methyl]-8-hydroxyquinoline,along with their associated therapeutic agents,are further discussed.Ultimately,we collate evidence that copper homeostasis may function in the underlying etiology of several neurodegenerative diseases and offer novel insights into the potential prevention and treatment of these diseases based on copper homeostasis.
文摘Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings.
基金funded by NIH-NIA R01AG061708 (to PHO)Patrick Grange Memorial Foundation (to PHO)+1 种基金A Long Swim (to PHO)CureSPG4 Foundation (to PHO)。
文摘Developing effective and long-term treatment strategies for rare and complex neurodegenerative diseases is challenging. One of the major roadblocks is the extensive heterogeneity among patients. This hinders understanding the underlying disease-causing mechanisms and building solutions that have implications for a broad spectrum of patients. One potential solution is to develop personalized medicine approaches based on strategies that target the most prevalent cellular events that are perturbed in patients. Especially in patients with a known genetic mutation, it may be possible to understand how these mutations contribute to problems that lead to neurodegeneration. Protein–protein interaction analyses offer great advantages for revealing how proteins interact, which cellular events are primarily involved in these interactions, and how they become affected when key genes are mutated in patients. This line of investigation also suggests novel druggable targets for patients with different mutations. Here, we focus on alsin and spastin, two proteins that are identified as “causative” for amyotrophic lateral sclerosis and hereditary spastic paraplegia, respectively, when mutated. Our review analyzes the protein interactome for alsin and spastin, the canonical pathways that are primarily important for each protein domain, as well as compounds that are either Food and Drug Administration–approved or are in active clinical trials concerning the affected cellular pathways. This line of research begins to pave the way for personalized medicine approaches that are desperately needed for rare neurodegenerative diseases that are complex and heterogeneous.
基金supported by the National Natural Science Foundation of China,Nos.82171363,82371381(to PL),82171458(to XJ)Key Research and Development Project of Shaa nxi Province,Nos.2024SF-YBXM-404(to KY)。
文摘Recent advances in research on extracellular vesicles have significantly enhanced their potential as therapeutic agents for neurological diseases.Owing to their therapeutic properties and ability to cross the blood–brain barrier,extracellular vesicles are recognized as promising drug delivery vehicles for various neurological conditions,including ischemic stroke,traumatic brain injury,neurodegenerative diseases,glioma,and psychosis.However,the clinical application of natural extracellular vesicles is hindered by their limited targeting ability and short clearance from the body.To address these limitations,multiple engineering strategies have been developed to enhance the targeting capabilities of extracellular vesicles,thereby enabling the delivery of therapeutic contents to specific tissues or cells.Therefore,this review aims to highlight the latest advancements in natural and targeting-engineered extracellular vesicles,exploring their applications in treating traumatic brain injury,ischemic stroke,Parkinson's disease,Alzheimer's disease,amyotrophic lateral sclerosis,glioma,and psychosis.Additionally,we summarized recent clinical trials involving extracellular vesicles and discussed the challenges and future prospects of using targeting-engineered extracellular vesicles for drug delivery in treating neurological diseases.This review offers new insights for developing highly targeted therapies in this field.
基金supported by the National Natural Science Foundation of China, Nos. 82271411 (to RG), 51803072 (to WLiu)grants from the Department of Finance of Jilin Province, Nos. 2022SCZ25 (to RG), 2022SCZ10 (to WLiu), 2021SCZ07 (to RG)+2 种基金Jilin Provincial Science and Technology Program, No. YDZJ202201ZYTS038 (to WLiu)The Youth Support Programmed Project of China-Japan Union Hospital of Jilin University, No. 2022qnpy11 (to WLuo)The Project of China-Japan Union Hospital of Jilin University, No. XHQMX20233 (to RG)
文摘Various nanoparticle-based drug delivery systems for the treatment of neurological disorders have been widely studied.However,their inability to cross the blood–brain barrier hampers the clinical translation of these therapeutic strategies.Liposomes are nanoparticles composed of lipid bilayers,which can effectively encapsulate drugs and improve drug delivery across the blood–brain barrier and into brain tissue through their targeting and permeability.Therefore,they can potentially treat traumatic and nontraumatic central nervous system diseases.In this review,we outlined the common properties and preparation methods of liposomes,including thin-film hydration,reverse-phase evaporation,solvent injection techniques,detergent removal methods,and microfluidics techniques.Afterwards,we comprehensively discussed the current applications of liposomes in central nervous system diseases,such as Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis,traumatic brain injury,spinal cord injury,and brain tumors.Most studies related to liposomes are still in the laboratory stage and have not yet entered clinical trials.Additionally,their application as drug delivery systems in clinical practice faces challenges such as drug stability,targeting efficiency,and safety.Therefore,we proposed development strategies related to liposomes to further promote their development in neurological disease research.
文摘Amyotrophic lateral sclerosis(ALS)is a neuromuscular condition resulting from the progressive degeneration of motor neurons in the cortex,brainstem,and spinal cord.While the typical clinical phenotype of ALS involves both upper and lower motor neurons,human and animal studies over the years have highlighted the potential spread to other motor and non-motor regions,expanding the phenotype of ALS.Although superoxide dismutase 1(SOD1)mutations represent a minority of ALS cases,the SOD1 gene remains a milestone in ALS research as it represents the first genetic target for personalized therapies.Despite numerous single case reports or case series exhibiting extramotor symptoms in patients with ALS mutations in SOD1(SOD1-ALS),no studies have comprehensively explored the full spectrum of extramotor neurological manifestations in this subpopulation.In this narrative review,we analyze and discuss the available literature on extrapyramidal and non-motor features during SOD1-ALS.The multifaceted expression of SOD1 could deepen our understanding of the pathogenic mechanisms,pointing towards a multidisciplinary approach for affected patients in light of new therapeutic strategies for SOD1-ALS.
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, the neurotransmitters that act on them, their electrical activity,and the neural circuits they form can guide the search for new multi-target drugs to treat Parkinson's disease in clinical practice. Examining the potential intra-nuclear and neural circuit mechanisms of deep brain stimulation associated with the globus pallidus can facilitate the management of both motor and non-motor symptoms while minimizing the side effects caused by deep brain stimulation.
基金supported by the National Natural Science Foundation of China,Nos.82071426,81873784Clinical Cohort Construction Program of Peking University Third Hospital,No.BYSYDL2019002(all to DF)。
文摘Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor neurons.Early bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to bed.However,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is unclear.To address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral sclerosis.We used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis patients.Multiple factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb involvement.The results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis patients.These findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.
文摘Functional asymmetries, for example, the preferential involvement of 1 brain hemisphere to process stimuli, may increase brain efficiency and the capacity to carry out tasks simultaneously. We investigated which hemisphere was primarily invoIved in processing acoustic stimuli in goats using a headorienting paradigm. Three playbacks using goat vocalizations recorded in different contexts: food anticipation (positive), isolation (negative), food frustration (negative), as well as 1 playback involving dog barks (negative) were presented on the left and right sides of the test subjects simultaneously. The head-orienting response (left or right) and latency to resume feeding were recorded. The direction of the head-orienting response did not differ between the various playbacks. However, when the head-orienting response was tested against chanee level, goats showed a right bias regardless of the stimuli presented. Goats responded more to dog barks than to food frustration calls, whereas responses to food anticipation and isolation calls were intermediate. In addition, the latency to resume feeding, an indicator of fear reaction, was not affected by the kind of vocalization presented. These results provide evidence for asymmetries in goat vocal perceptio n of emotional-li nked con specific and heterospecific calls. They also suggest involvement of the left brain hemisphere for processing acoustic stimuli, which might have been perceived as familiar and non -threate ning.
基金supported by the Russian Science Foundation(grant no.19-14-00119)The complex expeditions on Kolguev Island for wildfowl population monitoring were supported by Vogelschutz-Komitee and Conservation Bundesamt fur Naturschutz,BfN,(MEERESENTEN grant 3516821500).
文摘Behavioural lateralization,which reflects the functional specializations of the two brain hemispheres,is assumed to play an important role in cooperative intraspecific interactions.However,there are few studies focused on the lateralization in cooperative behaviours of individuals,especially in a natural setting.In the present study,we investigated Iateralized spatial interactions between the partners in life-long monogamous pairs.The male-female pairs of two geese species(barnacle,Branta leucopsis,and white-fronted,Anser albifrons geese),were observed during different stages of the annual cycle in a variety of conditions.In geese flocks,we recorded which visual hemifield(left/right)the following partner used to monitor the leading partner relevant to the type of behaviour and the disturbance factors.In a significant majority of pairs,the following bird viewed the leading partner with the left eye during routine behaviours such as resting and feeding in undisturbed conditions.This behavioural lateralization,implicating the right hemisphere processing,was consistent across the different aggregation sites and years of the study.In contrast,no significant bias was found in a variety of geese behaviours associated with enhanced disturbance(when alert on water,flying or fleeing away when disturbed,feeding during the hunting period,in urban area feeding and during moulting).We hypothesize that the increased demands for right hemisphere processing to deal with stressful and emergency situations may interfere with the manifestation of lateralization in social interactions.