Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,...Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.展开更多
Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to ...Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.展开更多
Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s dis...Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.展开更多
Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular me...Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.展开更多
Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor corte...Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.展开更多
29,164,578 people are living in Nepal.Out of them,48.96%are men and 51.04%are women.The growth rate of the population is 0.93%annually.However,216,957 individuals had been abroad for employment,education or other reas...29,164,578 people are living in Nepal.Out of them,48.96%are men and 51.04%are women.The growth rate of the population is 0.93%annually.However,216,957 individuals had been abroad for employment,education or other reasons.It has developed an addiction to imported products using remittances.The government delays spending the money allotted for capital improvements.The debt incurred by loans received from donors exceeds between 20 trillion and 80 billion of Nepal’s entire yearly budget.Based on statistics from Nepal Rastra Bank fiscal years 2021/2022,export and import contributions to overall Nepal’s foreign commerce were 8.40%and 91.60%,respectively.Due to the burden of debt and increasing trade deficit in the Nepalese economy,it has greatly affected the livelihood of the people.The increase in the prices of goods has made the lives of ordinary and low-income citizens very difficult.To reduce it,it is necessary to increase the production of indigenous products and promote their trade.Nepal needs to improve its ability to balance imports and exports.Economic dependency will reduce and the nation’s focus on self-sufficiency will increase if the market is extended by raising the output of locally produced items.There will be an increase in hazards as the state’s ability to function weakens.No nation can be entirely self-sufficient in the open global market of today by producing all the commodities and services it requires.Economic dependency will reduce and the nation’s focus on self-sufficiency will increase if the market is extended by raising the output of locally produced items.There will be an increase in hazards as the state’s ability to function weakens.展开更多
The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intr...The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.展开更多
In order to study the detonation velocity deficits of bending flexible detonating fuses,a physical model and a theoretical mathematical equation of detonation velocity deficits for bending flexible detonation fuses we...In order to study the detonation velocity deficits of bending flexible detonating fuses,a physical model and a theoretical mathematical equation of detonation velocity deficits for bending flexible detonation fuses were established based on the detonation wave's corner effects and delay time phenomenon by using non-dimensional analysis method.Besides,a semi-empirical formula of detonation velocity deficit for bending fuses in the same charge size was obtained through experiment and curve fitting.The result shows that an exponential relationship between the detonation velocity deficits and reciprocal of curvature radius.展开更多
Schizophrenia is a typical mental disorder characterized by cognitive,social,and emotional impairments and by psychotic symptoms.For nearly a century,there have been ongoing discussions on the anatomical-functional co...Schizophrenia is a typical mental disorder characterized by cognitive,social,and emotional impairments and by psychotic symptoms.For nearly a century,there have been ongoing discussions on the anatomical-functional connections between brain abnormalities and symptoms in patients with schizophrenia.Neuroimaging studies in such patients show abnormalities in the prefrontal cortex(PFC),a brain region that acts as an executive center in cognition processing.The disrupted brain connectivity between PFC and other brain structures(such as the limbic system,basal ganglia and thalamus)results in faulty information processing and cognition deficits.Dopamine receptors,which have historically acted as vital targets in schizophrenia therapies,have complex roles in cognition.Here we reviewed dopamine's role as a widespread neurotransmitter mediating the PFC-cognitive system.The imbalance of brain dopamine level,especially the abnormal D1/D2receptors ratio,leads to dysfunctions in brain connectivity in patients with schizophrenia.Recent neurocognitive modeling studies suggest the imbalance of dopamine receptors affects the internal noise within brain networks,which may lead to reduced signal-to-noise ratio in the PFC neuron populations.Going forward,more researches focusing on the relationship between pharmacology and neurocognitive models are needed,in an effort to identify more effective and efficient ways to treat cognitive impairment in patients with schizophrenia.展开更多
Dear Editor,We read with great interest article titled"Anisometropia magnitude and visual deficits in previously untreated anisometropic amblyopia"by Chen et al[1].The authors have analysed subjects with pre...Dear Editor,We read with great interest article titled"Anisometropia magnitude and visual deficits in previously untreated anisometropic amblyopia"by Chen et al[1].The authors have analysed subjects with previously untreated anisometropic amblyopia and found a significant correlation between high degree of anisometropia and deep amblyopia,worse contrast sensitivity,fusion and stereopsis functions.We commend the authors in addressing a very important problem and agree with the authors in the notation that children with anisometropia are usually detected later owing to lack of noticeable physical abnormalities.展开更多
Introduction: Rural residents are at higher risk for a depressive disorder than their non-rural counterparts. Recent research has indicated that co-morbidities are also associated with depression. Health service defic...Introduction: Rural residents are at higher risk for a depressive disorder than their non-rural counterparts. Recent research has indicated that co-morbidities are also associated with depression. Health service deficits (HSDs) is an analytic concept that facilitates the examination of how a population uses health services relevant to their condition. A HSD is present when, over the preceding 12 months, an individual has had no health insurance, no specified health care provider, deferred medical care due to cost, or did not have a routine medical exam. Research has shown a high prevalence of HSDs in populations with individual chronic conditions. No study that we know of has examined if there is an association between the constellation of chronic conditions of depression and the co-morbidities of asthma, arthritis, and diabetes, with HSDs. Methods: 2011 Behavioral Risk Factor Surveillance Survey (BRFSS) data were analyzed to identify important dimensions of the epidemiology of depression by ascertaining whether there were differences in the prevalence of health service deficits in rural versus non-rural adults with depression and at least one additional chronic disease (arthritis, asthma, or diabetes). Data analyses entailed both bivariate and multivariate techniques. All analyses were performed on weighted data. Results: Logistic regression analysis performed using the presence of at least one HSD as the dependent variable yielded that for US adults with lifetime depression those who were African American, Hispanic and other/multiracial in comparison to Caucasian had higher odds of having at least one health service deficit. Low socioeconomic status (SES) and middle SES in comparison to high SES were also risk factors for US adults with lifetime depression having at least one HSD. Rural residency in comparison to non-rural residency also emerged as an independent risk factor (for US adults with lifetime depression having at least one HSD. Chronic disease, however, emerged as protective against US adults with lifetime depression having at least one health service deficit. Conclusions: This study demonstrated that race/ethnicity, SES, and rural residency are important predictors of health service deficits for individuals with a lifetime diagnosis of depression while having one or more chronic conditions for these same individuals was protective.展开更多
Background: Many instruments used to assess outcomes of treatment for Alzheimer’s disease (AD) have no published evidence of their relevance and content validity in earlier stages of the disease, i.e., mild cognitive...Background: Many instruments used to assess outcomes of treatment for Alzheimer’s disease (AD) have no published evidence of their relevance and content validity in earlier stages of the disease, i.e., mild cognitive impairment, or prodromal AD (pAD). The objective of this project was to evaluate the applicability and usefulness of the Perceived Deficits Questionnaire (PDQ) as an outcome measure in this population using qualitative methodology to support content validity. Method: Two waves of qualitative interviews were conducted in patients with MCI and pAD. Results: Evidence for content validity and usefulness of the instrument was demonstrated in the patient interviews. Minor modifications to the wording of several items were suggested for the PDQ and the recall period was changed. Conclusion: With these modifications, the PDQ has improved content validity and relevance. It is therefore a potentially useful outcome measure to evaluate therapeutic benefit in interventional studies of patients in the early stages of AD.展开更多
The purpose of this study was to determine if the substituted pyrimidine, CXB-909 (formerly known as KP544) which has been shown to amplify the effects of nerve growth factor in elevating choline-acetyltransferase act...The purpose of this study was to determine if the substituted pyrimidine, CXB-909 (formerly known as KP544) which has been shown to amplify the effects of nerve growth factor in elevating choline-acetyltransferase activity in vitro, could attenuate memory deficits in the mu-p-75 saporin injected mouse model of Alzheimer’s disease (AD). Seventy-one, seven-week old C57/BL6 mice received daily oral intubation of 10, 15, or 20 mg/kg CXB-909, or vehicle (0.5% methylcellulose solution), which continued for 32 days. At postnatal week nine, mice received bilateral intra-cerebroventricular injections of mu-p-75 saporin, or sterile phosphate buffered saline. Seven days after surgery, mice were trained for two days, on a cued-platform version of the Morris water maze task, and then tested on a four-day hidden-platform version, followed by a one-day probe version of this task. Mice injected with mu-p-75 saporin, had increased latency to find the hidden-platform compared to sham mice. Furthermore, mice treated with CXB-909 at the 10, and 15 mg/kg doses, significantly reduced their latency to reach the hidden-platform, compared to vehicle-treated mice given mu-p-75 saporin. These results suggest that CXB-909 can attenuate memory deficits in the mu-p-75 saporin injected mouse model of AD.展开更多
This study examines pragmatic language production deficits in people with Parkinson’s disease (PD). Participants (PD and non-PD) were interviewed and their responses coded for degree of informativeness. PD participan...This study examines pragmatic language production deficits in people with Parkinson’s disease (PD). Participants (PD and non-PD) were interviewed and their responses coded for degree of informativeness. PD participants weremore under-informative than non-PD participants. Response underinformativeness was associated with decreased executive control, mental status, and speech act comprehension measures. However, both speech act priming and utterance informativeness were strongly related to a measure of executive control, and when this variable (i.e., Stroop performance) was controlled, the correlation between speech act priming and utterance underinformativeness was no longer significant. It appears, then, that executive control deficits are related to the ability to comprehend and produce conversational utterances.展开更多
BACKGROUND: The use and abuse of designer drugs has been recognized for decades; however there are many derivatives of compounds that make their way into the community. Abuse of compound(s) known on the street as &quo...BACKGROUND: The use and abuse of designer drugs has been recognized for decades; however there are many derivatives of compounds that make their way into the community. Abuse of compound(s) known on the street as "bath salt" is on the rise.METHODS: We report the case of a 33-year-old man who complained of "flashbacks" and right arm shaking that followed a night of "bath salt" snorting. The active compound methylenedioxypyrovalerone methamphetamine(MDPV) was confirmed; however, analysis of three different "bath salt" products showed difference in their active components.RESULTS: The patient's symptoms remained stable and he was discharged home after observation in the emergency department with instructions to return for any symptom progression.CONCLUSION: Practitioners should be aware of the abuse of the compounds and that not all "bath salt" products contain MDPV.展开更多
Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be ...Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be blamed for these deficits.Exercise is widely recognized as promoting health and improving bad moods,but the mechanisms by which exercise affects SBI are still unclear.Methods:Lateral fluid percussion(LFP)method was used to fabricate moderate TBI in motor and somatosensory cortex of the C57 BL/6 J mice.A 4-weeks voluntary running wheel exercise with 6-day training per week was modified based on the previous protocols.Neurological status,sensorimotor function,spatial memory,electrophysiological,post-traumatic stress disorder(PTSD)associated anxiety and depression,cortical pathohistological changes were assessed to evaluate effects TBI and exercise intervention.Results:After moderate LFP injury,the TBI mice showed severe motor deficits at the early stage in acute phase but gradually recovered.During acute and subacute phase after TBI,novel object recognition(NOR)ability and spatial memory functions were consistently impaired in TBI mice;hippocampal firing frequency and burst probability were hampered.Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop.These electrophysiological impacts were associated with substantially lowered NOR preference as compared with the sham group during adulthood.4-weeks voluntary wheel running performed prior to induction of a moderate TBI,combined with 2 weeks voluntary motor skill training after TBI was found to inhibit plasma TNF-α,improve locomotor activity levels,alleviate anxiety and depression and promote spatial working memory recovery in rodents.At the meantime,histopathological deterioration was eased in the hippocampus in exercised mice.Conclusion:moderate TBI could induce neurological and neurobehavior impairments in mice.Aerobic exercise rehabilitation alleviated above mentioned deficits and may be an effective supplemental invention treatment for TBI patients.展开更多
RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/re...RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.展开更多
Background: Magnocellular deficit theory is among the different hypotheses that have been proposed to explain the pathophysiology of developmental dyslexia (DD). Dysfunction of the magnocellular system in DD has been ...Background: Magnocellular deficit theory is among the different hypotheses that have been proposed to explain the pathophysiology of developmental dyslexia (DD). Dysfunction of the magnocellular system in DD has been investigated using mainly visual evoked potentials (VEPs), particularly transient VEPs, although recently abnormal steady-state VEPs have also been reported. The brain regions responsible for the abnormal VEPs in DD have yet to be elucidated, however. In this study, we performed functional magnetic resonance imaging and electroencephalography (fMRI-EEG) simultaneously to elucidate the brain areas that were found in a previous study to be activated through stimulation of the magnocellular system, and then investigated the mechanism involved in the dysfunction seen in DD.Methods: Subjects were 20 healthy individuals (TYP group;13 men, 7 women;mean ± standard deviation age, 26.3 ± 5.53 years) and 2 men with DD (aged 42 and 30 years). Images of brain activity were acquired with 3-Tesla MRI while the viewing the reversal of low-spatial frequency and low-contrast black-and-white sinusoidal gratings. EEG was recorded concurrently to obtain steady-state VEPs.Results: Stimulus frequency-dependent VEPs were observed in the posterior region of the brain in the TYP group;however, VEP amplitudes in both DD patients were clearly smaller than those in TYP. fMRI images revealed that both the primary and secondary visual cortices were activated by black-and- white sinusoidal gratings in the TYP group, whereas activity in the visual cortex overall was reduced in both DD patients.Conclusions: Present low spatial and high reversal frequency visual stimuli activated the primary visual cortex presumably through predominant activation of the magnocellular pathway. This finding indicates that some cases of adult patients of DD involve impairment of the visual magnocellular system.展开更多
Social functioning is a key domain of impairment in both autism spectrum disorder(ASD)and attention-deficit/hyperactivity disorder(ADHD).This review adopts the social information-processing model as the theoretical fr...Social functioning is a key domain of impairment in both autism spectrum disorder(ASD)and attention-deficit/hyperactivity disorder(ADHD).This review adopts the social information-processing model as the theoretical framework to compare and contrast the deficits of ASD and ADHD at each of the six steps of social information-processing.Both disorders show deficits at each step,but the nature and origins of the deficits are different.Thus,while both disorders exhibit a common outcome of social impairment,the exact pathways that each disorder traverses along the six steps of social information-processing are different.For ASD,there is a social knowledge/behaviour deficit arising from difficulties in social/emotional cue detection,encoding,and interpretation,leading to problems in joining and initiating social interaction.For ADHD,there is a performance deficit incurred by disruption arising from the ADHD symptoms of inattention and hyperactivity/impulsivity,while its acquisition capacity on social knowledge is relatively intact.The inattentive,intrusive,and impulsive behaviours of ADHD unsettle social interaction.Finally,this review proposes training targets for intervention along the six steps of the social information-processing model for ASD and ADHD,as well as areas for future research in further elucidating the social impairment of the two disorders.展开更多
Brain injury-induced neurological deficits typically develop on the contralateral side of the body and include abnormal posture,motor weakness,and spasticity.It is believed that the interruption of descending neural p...Brain injury-induced neurological deficits typically develop on the contralateral side of the body and include abnormal posture,motor weakness,and spasticity.It is believed that the interruption of descending neural pathways that convey supraspinal commands to the motoneurons in the spinal cord is the main cause of these deficits.展开更多
文摘Parkinsonism by unilateral,intranigralβ-sitosterolβ-D-glucoside administration in rats is distinguished in that theα-synuclein insult begins unilaterally but spreads bilaterally and increases in severity over time,thus replicating several clinical features of Parkinson’s disease,a typicalα-synucleinopathy.As Nurr1 repressesα-synuclein,we evaluated whether unilateral transfected of rNurr1-V5 transgene via neurotensin-polyplex to the substantia nigra on day 30 after unilateralβ-sitosterolβ-D-glucoside lesion could affect bilateral neuropathology and sensorimotor deficits on day 30 post-transfection.This study found that rNurr1-V5 expression but not that of the green fluorescent protein(the negative control)reducedβ-sitosterolβ-D-glucoside-induced neuropathology.Accordingly,a bilateral increase in tyrosine hydroxylase-positive cells and arborization occurred in the substantia nigra and increased tyrosine hydroxylase-positive ramifications in the striatum.In addition,tyrosine hydroxylase-positive cells displayed less senescence markerβ-galactosidase and more neuron-cytoskeleton markerβIII-tubulin and brain-derived neurotrophic factor.A significant decrease in activated microglia(positive to ionized calcium-binding adaptor molecule 1)and neurotoxic astrocytes(positive to glial fibrillary acidic protein and complement component 3)and increased neurotrophic astrocytes(positive to glial fibrillary acidic protein and S100 calcium-binding protein A10)also occurred in the substantia nigra.These effects followed the bilateral reduction inα-synuclein aggregates in the nigrostriatal system,improving sensorimotor behavior.Our results show that unilateral rNurr1-V5 transgene expression in nigral dopaminergic neurons mitigates bilateral neurodegeneration(senescence and loss of neuron-cytoskeleton and tyrosine hydroxylase-positive cells),neuroinflammation(activated microglia,neurotoxic astrocytes),α-synuclein aggregation,and sensorimotor deficits.Increased neurotrophic astrocytes and brain-derived neurotrophic factor can mediate the rNurr1-V5 effect,supporting its potential clinical use in the treatment of Parkinson’s disease.
基金supported by grants from the Ministerio de Economia y Competitividad(BFU2013-43458-R)Junta de Andalucia(P12-CTS-1694 and Proyexcel-00422)to ZUK。
文摘Memory deficit,which is often associated with aging and many psychiatric,neurological,and neurodegenerative diseases,has been a challenging issue for treatment.Up till now,all potential drug candidates have failed to produce satisfa ctory effects.Therefore,in the search for a solution,we found that a treatment with the gene corresponding to the RGS14414protein in visual area V2,a brain area connected with brain circuits of the ventral stream and the medial temporal lobe,which is crucial for object recognition memory(ORM),can induce enhancement of ORM.In this study,we demonstrated that the same treatment with RGS14414in visual area V2,which is relatively unaffected in neurodegenerative diseases such as Alzheimer s disease,produced longlasting enhancement of ORM in young animals and prevent ORM deficits in rodent models of aging and Alzheimer’s disease.Furthermore,we found that the prevention of memory deficits was mediated through the upregulation of neuronal arbo rization and spine density,as well as an increase in brain-derived neurotrophic factor(BDNF).A knockdown of BDNF gene in RGS14414-treated aging rats and Alzheimer s disease model mice caused complete loss in the upregulation of neuronal structural plasticity and in the prevention of ORM deficits.These findings suggest that BDNF-mediated neuronal structural plasticity in area V2 is crucial in the prevention of memory deficits in RGS14414-treated rodent models of aging and Alzheimer’s disease.Therefore,our findings of RGS14414gene-mediated activation of neuronal circuits in visual area V2 have therapeutic relevance in the treatment of memory deficits.
基金supported in parts by the National Natural Science Foundation of China,Nos.82101501(to QF),and 82201589(to XH)。
文摘Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.
基金supported by the National Natural Science Foundation of China, No. 81771140 (to YDZ)the Natural Science Foundation of Jiangsu Province of China, No. BK20201117 (to YDZ)Jiangsu “Six One Project” for Distinguished Medical Scholars of China, No. LGY2020013 (to TJ)
文摘Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.
基金supported by Consejo Nacional de Ciencia y Tecnología(CONACy T)project CB 2016-287614(to RGP and ABN)by Scholarship Programa de Apoyo a Proyectos de Investigación e Innovación Tecnológica de la Universidad Nacional Autónoma de México(PAPIIT-UNAM)IA203319 and PAPIIT-UNAM IN216221 to(LERL)。
文摘Norepinephrine plays an important role in motor functional recovery after a brain injury caused by ferrous chloride.Inhibition of norepinephrine release by clonidine is correlated with motor deficits after motor cortex injury.The aim of this study was to analyze the role ofα-adrenergic receptors in the restoration of motor deficits in recovering rats after brain damage.The rats were randomly assigned to the sham and injury groups and then treated with the following pharmacological agents at 3 hours before and 8 hours,3 days,and 20 days after ferrous chloride-induced cortical injury:saline,clonidine,efaroxan(a selective antagonist ofα-adrenergic receptors)and clonidine+efaroxan.The sensorimotor score,the immunohistochemical staining forα-adrenergic receptors,and norepinephrine levels were evaluated.Eight hours post-injury,the sensorimotor score and norepinephrine levels in the locus coeruleus of the injured rats decreased,and these effects were maintained 3 days post-injury.However,20 days later,clonidine administration diminished norepinephrine levels in the pons compared with the sham group.This effect was accompanied by sensorimotor deficits.These effects were blocked by efaroxan.In conclusion,an increase inα-adrenergic receptor levels was observed after injury.Clonidine restores motor deficits in rats recovering from cortical injury,an effect that was prevented by efaroxan.The underlying mechanisms involve the stimulation of hypersensitiveα-adrenergic receptors and inhibition of norepinephrine activity in the locus coeruleus.The results of this study suggest thatαreceptor agonists might restore deficits or impede rehabilitation in patients with brain injury,and therefore pharmacological therapies need to be prescribed cautiously to these patients.
文摘29,164,578 people are living in Nepal.Out of them,48.96%are men and 51.04%are women.The growth rate of the population is 0.93%annually.However,216,957 individuals had been abroad for employment,education or other reasons.It has developed an addiction to imported products using remittances.The government delays spending the money allotted for capital improvements.The debt incurred by loans received from donors exceeds between 20 trillion and 80 billion of Nepal’s entire yearly budget.Based on statistics from Nepal Rastra Bank fiscal years 2021/2022,export and import contributions to overall Nepal’s foreign commerce were 8.40%and 91.60%,respectively.Due to the burden of debt and increasing trade deficit in the Nepalese economy,it has greatly affected the livelihood of the people.The increase in the prices of goods has made the lives of ordinary and low-income citizens very difficult.To reduce it,it is necessary to increase the production of indigenous products and promote their trade.Nepal needs to improve its ability to balance imports and exports.Economic dependency will reduce and the nation’s focus on self-sufficiency will increase if the market is extended by raising the output of locally produced items.There will be an increase in hazards as the state’s ability to function weakens.No nation can be entirely self-sufficient in the open global market of today by producing all the commodities and services it requires.Economic dependency will reduce and the nation’s focus on self-sufficiency will increase if the market is extended by raising the output of locally produced items.There will be an increase in hazards as the state’s ability to function weakens.
文摘The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.
基金Supported by the Foundation of State Key Laboratory of Explosion Science and Technology(YBKT10-04)
文摘In order to study the detonation velocity deficits of bending flexible detonating fuses,a physical model and a theoretical mathematical equation of detonation velocity deficits for bending flexible detonation fuses were established based on the detonation wave's corner effects and delay time phenomenon by using non-dimensional analysis method.Besides,a semi-empirical formula of detonation velocity deficit for bending fuses in the same charge size was obtained through experiment and curve fitting.The result shows that an exponential relationship between the detonation velocity deficits and reciprocal of curvature radius.
文摘Schizophrenia is a typical mental disorder characterized by cognitive,social,and emotional impairments and by psychotic symptoms.For nearly a century,there have been ongoing discussions on the anatomical-functional connections between brain abnormalities and symptoms in patients with schizophrenia.Neuroimaging studies in such patients show abnormalities in the prefrontal cortex(PFC),a brain region that acts as an executive center in cognition processing.The disrupted brain connectivity between PFC and other brain structures(such as the limbic system,basal ganglia and thalamus)results in faulty information processing and cognition deficits.Dopamine receptors,which have historically acted as vital targets in schizophrenia therapies,have complex roles in cognition.Here we reviewed dopamine's role as a widespread neurotransmitter mediating the PFC-cognitive system.The imbalance of brain dopamine level,especially the abnormal D1/D2receptors ratio,leads to dysfunctions in brain connectivity in patients with schizophrenia.Recent neurocognitive modeling studies suggest the imbalance of dopamine receptors affects the internal noise within brain networks,which may lead to reduced signal-to-noise ratio in the PFC neuron populations.Going forward,more researches focusing on the relationship between pharmacology and neurocognitive models are needed,in an effort to identify more effective and efficient ways to treat cognitive impairment in patients with schizophrenia.
文摘Dear Editor,We read with great interest article titled"Anisometropia magnitude and visual deficits in previously untreated anisometropic amblyopia"by Chen et al[1].The authors have analysed subjects with previously untreated anisometropic amblyopia and found a significant correlation between high degree of anisometropia and deep amblyopia,worse contrast sensitivity,fusion and stereopsis functions.We commend the authors in addressing a very important problem and agree with the authors in the notation that children with anisometropia are usually detected later owing to lack of noticeable physical abnormalities.
文摘Introduction: Rural residents are at higher risk for a depressive disorder than their non-rural counterparts. Recent research has indicated that co-morbidities are also associated with depression. Health service deficits (HSDs) is an analytic concept that facilitates the examination of how a population uses health services relevant to their condition. A HSD is present when, over the preceding 12 months, an individual has had no health insurance, no specified health care provider, deferred medical care due to cost, or did not have a routine medical exam. Research has shown a high prevalence of HSDs in populations with individual chronic conditions. No study that we know of has examined if there is an association between the constellation of chronic conditions of depression and the co-morbidities of asthma, arthritis, and diabetes, with HSDs. Methods: 2011 Behavioral Risk Factor Surveillance Survey (BRFSS) data were analyzed to identify important dimensions of the epidemiology of depression by ascertaining whether there were differences in the prevalence of health service deficits in rural versus non-rural adults with depression and at least one additional chronic disease (arthritis, asthma, or diabetes). Data analyses entailed both bivariate and multivariate techniques. All analyses were performed on weighted data. Results: Logistic regression analysis performed using the presence of at least one HSD as the dependent variable yielded that for US adults with lifetime depression those who were African American, Hispanic and other/multiracial in comparison to Caucasian had higher odds of having at least one health service deficit. Low socioeconomic status (SES) and middle SES in comparison to high SES were also risk factors for US adults with lifetime depression having at least one HSD. Rural residency in comparison to non-rural residency also emerged as an independent risk factor (for US adults with lifetime depression having at least one HSD. Chronic disease, however, emerged as protective against US adults with lifetime depression having at least one health service deficit. Conclusions: This study demonstrated that race/ethnicity, SES, and rural residency are important predictors of health service deficits for individuals with a lifetime diagnosis of depression while having one or more chronic conditions for these same individuals was protective.
文摘Background: Many instruments used to assess outcomes of treatment for Alzheimer’s disease (AD) have no published evidence of their relevance and content validity in earlier stages of the disease, i.e., mild cognitive impairment, or prodromal AD (pAD). The objective of this project was to evaluate the applicability and usefulness of the Perceived Deficits Questionnaire (PDQ) as an outcome measure in this population using qualitative methodology to support content validity. Method: Two waves of qualitative interviews were conducted in patients with MCI and pAD. Results: Evidence for content validity and usefulness of the instrument was demonstrated in the patient interviews. Minor modifications to the wording of several items were suggested for the PDQ and the recall period was changed. Conclusion: With these modifications, the PDQ has improved content validity and relevance. It is therefore a potentially useful outcome measure to evaluate therapeutic benefit in interventional studies of patients in the early stages of AD.
文摘The purpose of this study was to determine if the substituted pyrimidine, CXB-909 (formerly known as KP544) which has been shown to amplify the effects of nerve growth factor in elevating choline-acetyltransferase activity in vitro, could attenuate memory deficits in the mu-p-75 saporin injected mouse model of Alzheimer’s disease (AD). Seventy-one, seven-week old C57/BL6 mice received daily oral intubation of 10, 15, or 20 mg/kg CXB-909, or vehicle (0.5% methylcellulose solution), which continued for 32 days. At postnatal week nine, mice received bilateral intra-cerebroventricular injections of mu-p-75 saporin, or sterile phosphate buffered saline. Seven days after surgery, mice were trained for two days, on a cued-platform version of the Morris water maze task, and then tested on a four-day hidden-platform version, followed by a one-day probe version of this task. Mice injected with mu-p-75 saporin, had increased latency to find the hidden-platform compared to sham mice. Furthermore, mice treated with CXB-909 at the 10, and 15 mg/kg doses, significantly reduced their latency to reach the hidden-platform, compared to vehicle-treated mice given mu-p-75 saporin. These results suggest that CXB-909 can attenuate memory deficits in the mu-p-75 saporin injected mouse model of AD.
文摘This study examines pragmatic language production deficits in people with Parkinson’s disease (PD). Participants (PD and non-PD) were interviewed and their responses coded for degree of informativeness. PD participants weremore under-informative than non-PD participants. Response underinformativeness was associated with decreased executive control, mental status, and speech act comprehension measures. However, both speech act priming and utterance informativeness were strongly related to a measure of executive control, and when this variable (i.e., Stroop performance) was controlled, the correlation between speech act priming and utterance underinformativeness was no longer significant. It appears, then, that executive control deficits are related to the ability to comprehend and produce conversational utterances.
文摘BACKGROUND: The use and abuse of designer drugs has been recognized for decades; however there are many derivatives of compounds that make their way into the community. Abuse of compound(s) known on the street as "bath salt" is on the rise.METHODS: We report the case of a 33-year-old man who complained of "flashbacks" and right arm shaking that followed a night of "bath salt" snorting. The active compound methylenedioxypyrovalerone methamphetamine(MDPV) was confirmed; however, analysis of three different "bath salt" products showed difference in their active components.RESULTS: The patient's symptoms remained stable and he was discharged home after observation in the emergency department with instructions to return for any symptom progression.CONCLUSION: Practitioners should be aware of the abuse of the compounds and that not all "bath salt" products contain MDPV.
文摘Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be blamed for these deficits.Exercise is widely recognized as promoting health and improving bad moods,but the mechanisms by which exercise affects SBI are still unclear.Methods:Lateral fluid percussion(LFP)method was used to fabricate moderate TBI in motor and somatosensory cortex of the C57 BL/6 J mice.A 4-weeks voluntary running wheel exercise with 6-day training per week was modified based on the previous protocols.Neurological status,sensorimotor function,spatial memory,electrophysiological,post-traumatic stress disorder(PTSD)associated anxiety and depression,cortical pathohistological changes were assessed to evaluate effects TBI and exercise intervention.Results:After moderate LFP injury,the TBI mice showed severe motor deficits at the early stage in acute phase but gradually recovered.During acute and subacute phase after TBI,novel object recognition(NOR)ability and spatial memory functions were consistently impaired in TBI mice;hippocampal firing frequency and burst probability were hampered.Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop.These electrophysiological impacts were associated with substantially lowered NOR preference as compared with the sham group during adulthood.4-weeks voluntary wheel running performed prior to induction of a moderate TBI,combined with 2 weeks voluntary motor skill training after TBI was found to inhibit plasma TNF-α,improve locomotor activity levels,alleviate anxiety and depression and promote spatial working memory recovery in rodents.At the meantime,histopathological deterioration was eased in the hippocampus in exercised mice.Conclusion:moderate TBI could induce neurological and neurobehavior impairments in mice.Aerobic exercise rehabilitation alleviated above mentioned deficits and may be an effective supplemental invention treatment for TBI patients.
基金supported by Clinical Study on Treatment of Cerebral Small Blood Vessel Disease by Integrated Traditional Chinese and Western Medicine,No.ZHYY-ZXYJHZX-201625
文摘RehabilNation training is believed to be beneficial to patients with stroke, but its molecular mechanism is still unclear. Rat models of cerebral ischemic stroke were established by middle cerebral artery occlusion/reperfusion, and then received treadmill training of different intens让ies, twice a day for 30 minutes for 1 week. Low-intensity training was conducted at 5 m/min, with a 10-minute running, 10-minute rest, and 10-minute running cycle. In the moderate-intensity training, the intensity gradually increased from 5 m/min to 10 m/min in 5 minutes, with the same rest cycle as above. In high-intensity training, the intensity gradually increased from 5 m/min to 25 m/min in 5 minutes, with the same rest cycle as above. The Bederson scale was used to evaluate the improvement of motor function. Infarct volume was detected using 2,3,5-triphenyltetrazolium chloride staining. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining was applied to detect the apoptosis of nerve cells in brain tissue. Western blot assay was employed to analyze the activation of cyclic adenosine monophosphate (cAMP)/protein kinase A and Akt/glycogen synthase kinase-3卩 signaling pathways in rat brain tissue. All training intensities reduced the neurological deficit score, infarct volume, and apoptosis in nerve cells in brain tissue of stroke rats. Training intensities activated the cAMP/protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This activation was more obvious with higher training intensities. These changes were reversed by intracerebroventricular injection of protein kinase A inhibitor Rp-cAMP. Our findings indicate that the neuroprotective effect of rehabilitation training is achieved via activation of the cAMP/ protein kinase A and Akt/glycogen synthase kinase-3 beta signaling pathways. This study was approved by the Ethics Committee of Animal Experimentation in Shanghai No. 8 Peoples Hospital, China.
文摘Background: Magnocellular deficit theory is among the different hypotheses that have been proposed to explain the pathophysiology of developmental dyslexia (DD). Dysfunction of the magnocellular system in DD has been investigated using mainly visual evoked potentials (VEPs), particularly transient VEPs, although recently abnormal steady-state VEPs have also been reported. The brain regions responsible for the abnormal VEPs in DD have yet to be elucidated, however. In this study, we performed functional magnetic resonance imaging and electroencephalography (fMRI-EEG) simultaneously to elucidate the brain areas that were found in a previous study to be activated through stimulation of the magnocellular system, and then investigated the mechanism involved in the dysfunction seen in DD.Methods: Subjects were 20 healthy individuals (TYP group;13 men, 7 women;mean ± standard deviation age, 26.3 ± 5.53 years) and 2 men with DD (aged 42 and 30 years). Images of brain activity were acquired with 3-Tesla MRI while the viewing the reversal of low-spatial frequency and low-contrast black-and-white sinusoidal gratings. EEG was recorded concurrently to obtain steady-state VEPs.Results: Stimulus frequency-dependent VEPs were observed in the posterior region of the brain in the TYP group;however, VEP amplitudes in both DD patients were clearly smaller than those in TYP. fMRI images revealed that both the primary and secondary visual cortices were activated by black-and- white sinusoidal gratings in the TYP group, whereas activity in the visual cortex overall was reduced in both DD patients.Conclusions: Present low spatial and high reversal frequency visual stimuli activated the primary visual cortex presumably through predominant activation of the magnocellular pathway. This finding indicates that some cases of adult patients of DD involve impairment of the visual magnocellular system.
文摘Social functioning is a key domain of impairment in both autism spectrum disorder(ASD)and attention-deficit/hyperactivity disorder(ADHD).This review adopts the social information-processing model as the theoretical framework to compare and contrast the deficits of ASD and ADHD at each of the six steps of social information-processing.Both disorders show deficits at each step,but the nature and origins of the deficits are different.Thus,while both disorders exhibit a common outcome of social impairment,the exact pathways that each disorder traverses along the six steps of social information-processing are different.For ASD,there is a social knowledge/behaviour deficit arising from difficulties in social/emotional cue detection,encoding,and interpretation,leading to problems in joining and initiating social interaction.For ADHD,there is a performance deficit incurred by disruption arising from the ADHD symptoms of inattention and hyperactivity/impulsivity,while its acquisition capacity on social knowledge is relatively intact.The inattentive,intrusive,and impulsive behaviours of ADHD unsettle social interaction.Finally,this review proposes training targets for intervention along the six steps of the social information-processing model for ASD and ADHD,as well as areas for future research in further elucidating the social impairment of the two disorders.
基金Novo Nordisk Foundation(0065099)the Swedish Science Research Council(K2014-62X-12190-19-5 and 2019-01771-3)。
文摘Brain injury-induced neurological deficits typically develop on the contralateral side of the body and include abnormal posture,motor weakness,and spasticity.It is believed that the interruption of descending neural pathways that convey supraspinal commands to the motoneurons in the spinal cord is the main cause of these deficits.
