39 article(s) in Neuroscience Research Notes

Neurocognitive Interventions Based On Network Neuroscience May Break The Cycle Of Drug Addiction Relapse

in malaysia, abstinence-centric programs failed to reduce drug use and stem the spread of hiv. the malaysian government shifted its focus to implement harm reduction strategies with methadone maintenance therapy (mmt), in particular proving to be effective in improving the overall health and well-being of people who inject drugs (pwids). despite this success, mmt retention rates remain low, as methadone is only able to stall drug consumption, but not stop it completely. neuroimaging research revealed that pwids enrolled in mmt still display addictive behavior, including drug cue sensitivity, craving, and withdrawal, despite treatment adherence. brain activity amongst treated pwids continues to bear similarities to untreated individuals, as they struggle with cognitive impairments and poor self-control. findings from the emerging field of network neuroscience could provide fresh insight into the mechanics of addiction, especially the impact of substance abuse on brain-wide cognitive networks. concurrently, the development of non-intrusive cognitive interventions, such as neurofeedback and transcranial magnetic stimulation, shows promise to reprogram a person's patterns of brain activity, including those regulated by large-scale networks, to a state resembling normalcy. we highlight the importance of relapse in the life-long rehabilitation of substance abuse. the lack of treatment options to handle relapse after successful harm-reduction policies is due to the absence of a conceptual framework to reason about interventions. we review recent research in the new field of network neuroscience, which suggests that altered brain activity due to drug addiction underlies the propensity for relapse and that this dysfunction is not addressed in drug rehabilitation programs. we hypothesize that non-invasive, non-pharmacological cognitive interventions based on network neuroscience to correct brain activity dysfunction associated with addiction are potential therapies to treat drug addiction relapse. in complement with medicine-substitution-based therapies, we hope this approach will finally break the cycle of addiction Show More ... ... Show Less

  • Brain Activity
  • Network Neuroscience
  • Drug Addiction
  • Substance Abuse
  • Cognitive Interventions
Improved Β-Catenin Detection In Spinal Cord Tissue Sections: Autofluorescence Quenching

experimental studies on spinal cord regeneration are focusing on the windows of opportunity to improve spinal cord microenvironment via spinal-centric repair pathways. one pathway of particular interest is the wnt/β-catenin signalling pathway which plays a vital role in axonal guidance, synaptic assembly and function, neuronal survival and connectivity after spinal cord trauma to induce repair. upregulation of β-catenin expression is often taken as evidence of regeneration mechanisms through the wnt/ β-catenin pathway. however, these studies may not have optimised the staining protocol for β-catenin to enable accurate detection of the protein. given possible issues with the background or endogenous tissue autofluorescence, there is a need to optimise the protocol further to allow better visualisation of β-catenin. so far, there are no studies which report optimising spinal cord tissues for β-catenin to reduce autofluorescence, and as β-catenin is widely used in spinal cord injury (sci) and other spinal cord tissue studies, thus it is an important issue to address. to achieve reliable detection and localisation of β-catenin, we utilised sequential quenching techniques using 1% nabh4 and 1mm cuso4 in 50mm ammonium acetate buffer to reduce both background and fixative-induced autofluorescence. our results showed that sequential autofluorescence quenching is crucial in β-catenin detection, and this improved technique indicates that β-catenin is localised in the spinal cord white matter regions. objective approach for the β-catenin localisation is highly significant as it unravelled an objective identification and illuminate the pattern of distribution of β-catenin for researcher focusing on spinal cord repair studies via the wnt/β-catenin pathway following sci Show More ... ... Show Less

  • Spinal Cord Tissue
  • Windows Of Opportunity
  • Cord Injury
  • Repair Pathways
Neuroscience Research Notes
  • 2020;
  • Neuroscience Research
MTRR Gene Variant Rs1801394 Found In Malaysian Patients With Neural Tube Defects

neural tube defects (ntds) are congenital anomalies resulting from the failure of neural tube closure during embryogenesis. the precise molecular mechanisms underlying this multifactorial disease is poorly understood, although single nucleotide polymorphisms in genes involved in the one-carbon metabolism cycle are believed to contribute towards ntd development. among them is 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (mtrr). protein function prediction algorithms (polyphen-2, provean, sift, smart-ensembl) were employed to evaluate its pathogenicity potential caused by the replacement of isoleucine with methionine. seven ntd patients and 12 of their parents were recruited for this study. dna samples were collected through blood or saliva whereby the extracted dnas were then sent for whole exome sequencing (wes). zygosity of the variant was confirmed from wes data of each subject and further validated through polymerase chain reaction (pcr) and sanger sequencing. the results revealed that 57% of patients and 83% of parents carried rs1801394 mutation in their mtrr gene, based on either homozygous (g/g) or heterozygous (a/g) genotypes. bioinformatics analysis of this missense mutation predicted that this change is damaging to mtrr protein function by 2 of the 3 predictor algorithms and that the change from isoleucine to methionine amino acid affects flavodoxin domain of the protein. this impacts enzyme activity within the one-carbon metabolism pathway, which is linked to the aetiology of ntds. from population databases, this variant was considered common with a maf >0.3, however, it was not found in the singapore genome variation project (sgvp), whose population is a closer representation of the malaysian subjects investigated here. hence, we explored the prevalence of this variant in other studies and found that its association with ntds differed across populations worldwide. finally, we conclude that rs1801394 may be an ntd risk factor in the malaysian population and should be further investigated as a potential prenatal screening tool Show More ... ... Show Less

  • Neural Tube Defects
  • Carbon Metabolism
  • Protein Function
  • The One
Moral Judgments In Obsessive-Compulsive Disorder: A Narrative Mini-Review

obsessive-compulsive disorder (ocd) is a prevalent mental disorder characterized by intrusive thoughts (obsessions) and ensuing rituals (compulsions). although oc patients exhibit various cognitive and behavioral problems, rigid and hypersensitive moral judgments are known to be one of the most striking problems in these patients. there is evidence indicating that oc patients often tend to make deontological judgments in moral dilemmas, significantly more than the healthy population. therefore, numerous studies are dedicated to understanding the underlying cognitive processes responsible for such variation of moral judgments in ocd, which are reviewed and discussed in the current paper. first, it is previously discussed that abnormal moral judgments in ocd are due to executive dysfunctions. these dysfunctions include impaired cognitive control resulting in the domination of strong, uncontrolled emotional responses, impaired cognitive flexibility resulting in the inability to switch between aspects of a scenario, and decreased capacity and overload of working memory and its inability to resist the interfering information. the dual-process theory also emphasizes and acknowledges the role of executive functions in moral judgments. second, it is thought that disobeying moral norms results in the abnormal feeling of deontological guilt in oc patients, to which these patients are highly sensitive. feeling of guilt is also thought to be correlated with ocd symptomatology. the third impairment contributing to abnormal moral judgments in ocd is known to be the abnormal feeling of disgust for moral violations and immoral unwanted intrusive thoughts, which is regarded as one of the major causes of ocd symptoms. finally, the abnormal fear of responsibility and being criticized due to not acting morally is regarded as one of the primary impairments contributing to the abnormal moral judgments in ocd. in conclusion, this review sheds light on the most striking cognitive and affective impairments contributing to abnormal moral judgments in ocd Show More ... ... Show Less

  • Moral Judgments
  • Obsessive Compulsive Disorder
  • Intrusive Thoughts
Sloreta Neurofeedback In Fibromyalgia

fibromyalgia is a chronic and incapacitating condition that produces, as main symptoms, pain, and stiffness. in addition to these physical symptoms, it is also accompanied by psychological symptoms such as cognitive deficits, anxiety, and depression. one of the non-pharmacological treatments that have been used in this pathology in recent years is neurofeedback. in this study, we analyze the efficacy of sloreta neurofeedback in the case of fibromyalgia. the experimental subject was a 37-year-old patient. quantified electroencephalography studies were applied on three occasions, one initial, another after fifteen days of waiting list, and another after treatment. psychometric scales were also applied at the same time to evaluate the patient's psychological and physical state. the treatment consisted of 5 sessions of neurofeedback loreta in brodmann area 2. after the treatment, a neurometric, psychometric, and clinical improvement were found. the improvement of the patient after 5 sessions is relevant since previous studies using neurofeedback in fibromyalgia, despite finding positive results, needed a higher number of sessions to achieve relevant results. therefore, the intervention with neurofeedback loreta in fibromyalgia patients could be an alternative or complement to current treatments Show More ... ... Show Less

  • Clinical Improvement
  • Cognitive Deficits
  • Physical State
  • Physical Symptoms
  • Positive Results
Dopamine Transporter 1 (DAT1) Rs40184 Single Nucleotide Polymorphism Is Not Associated With The Malaysian Major Depressive Disorder Subjects

major depressive disorder (mdd) is a serious mental illness with a multifactorial aetiology that was shown to influence behaviour and affect cognition. previous research has favoured the involvement of dopamine in the aetiology of the disorder, and since one of the critical regulators of the dopamine levels and activity in the brain is dat1, the present study investigated the association of a single nucleotide polymorphism in the dat1 gene (rs40184) and mdd in the malaysian population. a total of 300 cases and 300 matched controls were recruited from four klang valley hospitals and were screened for dat1 rs40184 using high resolution melting assays. the allele and genotype frequencies were analysed by using chi-square. hardy weinberg equilibrium for the distribution of alleles and genotypes was tested by using chi-square. determination of the association between rs40184 and mdd was achieved by conditional logistic regression using spss. in the present study, no significant association was obtained between dat1 and mdd in the malaysian population Show More ... ... Show Less

  • Single Nucleotide Polymorphism
  • Major Depressive Disorder
Research Beyond Biomedical Confines: Towards Better Mental Health And Well-Being For All

‘working together to prevent suicide’ is the theme of world mental health day 2019. according to the world health organisation, suicide is the second leading cause of death for people aged 15-19 years old. one person dies of suicide every 40 seconds, with this form of death affecting people of all age groups in all countries. hence in line with this year’s theme calling for a trans-sectoral and interdisciplinary approach to address this epidemic, we would like to invite all contributors and readers of neuroscience research notes (neuroscirn) to take a moment to reflect on how they - as researchers can contribute towards the facilitation, discussion and promotion of positive mental health, which in turn has been found to reduce suicide risk Show More ... ... Show Less

  • Mental Health
  • Cause Of Death
  • Suicide Risk
  • The World
  • Health And Well Being
Zinc Transporter-3 [SLC30A3 (Rs11126936)] Polymorphism Is Associated With Major Depressive Disorder In Asian Subjects

major depressive disorder (mdd) compromises the individual’s capacity for self-care and productivity. single nucleotide polymorphisms (snp) of a number of genes have been associated with mdd. the zinc transporter-3 protein, encoded by the znt3 (slc30a3) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of mdd. we hypothesise that variation in slc30a3 (rs11126936) snp increases risk of mdd. we recruited 300 mdd cases and 300 controls, matched in the ratio of 1:1 by age, gender and ethnicity. pcr-restriction fragment length polymorphism analysis was used in dna genotyping, validated by sequencing 10% of samples. deviation from the hardy-weinberg equilibrium was tested using the chi-square test. conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income. genotypes g/g and g/t showed two times greater odds of developing mdd compared to variant genotype t/t (or=1.983, 95% ci=1.031-3.815; p=0.040 and or=2.232, 95% ci=1.100-4.533; p=0.026 respectively). carriers of genotypes g/g and g/t of the snp rs11126936 in slc30a3 are associated with increased risk of mdd Show More ... ... Show Less

  • Major Depressive Disorder
  • Zinc Transporter
  • Restriction Fragment Length
Chemical Hypoxia In Human Pluripotent NT2 Stem Cell-Derived Neurons: Effect Of Hydroxamic Acid And Benzamide-Based Epigenetic Drugs

hypoxia-induced oxidative stress contributes to neuronal damage leading to many neurodegenerative disorders. hypoxia promotes many downstream effectors such as hypoxia-inducible factor-1α (hif-1α) in order to restore respiratory homeostasis due to low oxygen availability and increased ros. use of histone deacetylase (hdac) inhibitors may modulate hypoxia-induced neuronal cell damage.  in this study, we used two chemically diverse hdac inhibitors to investigate their effect on hypoxia-exposed neuronal cells. human pluripotent nt-2 stem cell-derived neuronal differentiated cells were exposed to cocl2 pre-treatment for 6h to induce hypoxia, prior to supplementation of hdac inhibitor (saha or mgcd0103). treatment with hdac inhibitor improved cell viability in hypoxia-induced neuronal cells. the increased hif1α expression in hypoxia-induced neuronal cells was blunted by these hdac inhibitors with a concomitant decrease in ros production. cocl2 treatment caused an increase in il-1β, which was significantly inhibited by these hdac inhibitors. furthermore, apoptosis induced in these cocl2 treated neuronal cells was mitigated by saha as well mgcd0103 suggesting that these hdac inhibitors are capable of reducing cellular toxicity, inflammation and apoptosis, and thus, could be beneficial as therapeutic molecules for many neuropathological conditions Show More ... ... Show Less

  • Hdac Inhibitors
  • Neuronal Cells
  • Stem Cell
  • Oxidative Stress
Genotypic And Phenotypic Variation Of CADASIL Among Chinese, Indians And Rungus In Malaysia

cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (cadasil) is a hereditary disease of small cerebral arteries. this case series aims to describe the mutations in notch3 and their phenotypes in malaysia. we included patients who were genetically confirmed to have cadasil, diagnosed at the university of malaya medical centre, malaysia. family members who fulfilled clinical or imaging criteria, and patients from two previous published malaysian families were also included. six families (eleven cases) were included in this series. genetic testing revealed notch3 mutations in c.328c>t (p.arg110cys, r110c), c.533t>g (p.cys185gly, c185g), c.1630c>t (p.arg544cys, r544c) and c.160c>t (p.arg54cys, r54c). two out of four chinese families had r544c mutation in exon 11, with a later age of onset, absence of migraine and lack of anterior temporal pole involvement on mri. one family with mixed indian and chinese ancestry had a mutation in exon 3 with r110c and another indian family exon 4 with c185g mutation. this case series highlights the genotypic and phenotypic variability of cadasil in a multiethnic country. the finding of p.arg544cys mutation among the older chinese families, similar to those reported in jeju island and taiwan, suggest the need to screen the older chinese stroke patients with typical mri changes Show More ... ... Show Less

  • Case Series
  • Chinese Families
  • Older Chinese
  • Genetic Testing
  • Exon 4
The Potential Of MLC901 (Neuroaid II™), A Traditional Chinese Medicine

stroke, also known as cerebral ischemia, is a common neurological disease. the therapeutic potential of mlc901 (neuroaid ii™) has been reported in clinical trials on traumatic brain injury as well as in animal and cell models. mlc901 reduced the infarction size, ischemia-induced neurological deficits and pro-inflammatory infiltration of phagocyte. it also inhibited the ischemia-induced expression of pro-inflammatory mediators and prx6, tlr4 signalling, and phosphorylation of nfκb. we found that the beneficial effects of mlc901 are in coherent with studies performed on the individual active ingredient. mlc901 may develop its efficacy through a synergistic effect via nine herbal extracts. mlc901 is a multifaceted traditional chinese medicine. a cocktail of herbs provides a broader spectrum of targets. this may surpass single-target drug treatment in terms of side effect and therapeutic efficacy. mlc901 leads to various potential research directions on the development or improvement of a feasible, effective and promising herbal formulation for treating stroke patients Show More ... ... Show Less

  • Traditional Chinese Medicine
  • Traumatic Brain Injury
  • Clinical Trials
  • Cerebral Ischemia
An Update On HLA Alleles As Pharmacogenetic Markers For Antiepileptic Drug-Induced Cutaneous Adverse Reaction

epilepsy is a common neurological disorder affecting approximately 50 million people worldwide. antiepileptic drugs (aeds) are commonly used to treat the disease depending, mainly on the type of seizure. however, the use of aeds may also lead to cutaneous adverse drug reactions (cadr) such as toxic epidermal necrolysis (ten), stevens–johnson syndrome (sjs), exfoliative dermatitis (ed) and drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms (dihs/dress), which are unwanted comorbidities in epilepsy. it was first discovered that the hla-b*15:02 allele was strongly associated with carbamazepine (cbz)-induced sjs/ten among han chinese and this led to the discovery of other hla alleles and cytochrome p450 (cyp) genes that were significantly associated with various aed-induced cadrs across various populations.  this mini review is an update on the latest findings of the involvement of various hla alleles and cyp alleles in cadrs caused by cbz, phenytoin (pht), oxcarbazepine (oxc) and lamitrogine (ltg) in different case-control studies around the world. from our review, we found that cbz- and pht-induced cadrs were more commonly reported than the other aeds. therefore, there were more robust pharmacogenetics studies related to these aeds. oxc- and ltg-induced cadrs were less commonly reported, and so more studies are needed to validate the reported association of the newer reported hla alleles with these aeds. it is also important to take into account the allelic frequency within a given population before drawing conclusions about the use of these alleles as genetic markers to prevent aed-induced cadr. overall, the current body of research point to a combination of alleles as a better pharmacogenetic marker compared to the use of a single gene as a genetic marker for aed-induced cadr Show More ... ... Show Less

  • Hla Alleles
  • Drug Induced
  • Adverse Reaction
  • Drug Reaction
  • The World
The Treatment Of Epileptic Seizures: The Potential Of Malaysian Medicinal Plants

epileptic seizures result from excessive brain activity and may affect sensory, motor and autonomic function; as well as, emotional state, memory, cognition or behaviour. effective anti-epileptic drugs (aeds) are available but have tolerability issues due to their side effects. medicinal plants are potential candidates for novel aeds, as many are traditional epilepsy remedies. malaysia is a megadiverse country, with many endemic plants serving as a large pool of potential candidates for the development of local herbal products. the large variety of flora make malaysia a prime location for the discovery of medicinal plants with anti-convulsive potential. this review lists 23 malaysian medicinal plants, of which four are used traditionally to treat epilepsy, without any scientific evidence. a further eight plants have no known traditional anti-epileptic use but have scientific evidence of its anti-epileptic activity. the remaining 11 plants possess both traditional use and scientific evidence. thus, this review identified several potential candidates for the development of novel aeds or enhancing current ones; as well as identified an imbalance between traditional use and scientific evidence. in addition, this review also identified several limitations in the reviewed studies and provided additional information to facilitate the design of future studies Show More ... ... Show Less

  • Medicinal Plants
  • Scientific Evidence
  • Epileptic Seizures
  • Traditional Use
  • Prime Location
Prospective Stem Cell Lines As In Vitro Neurodegenerative Disease Models For Natural Product Research

the use of in vitro model for screening pharmacological compounds or natural products has gained global interest.  the choice of cells to be manipulated plays a vital role in coming up with the best-suited model for specific diseases, including neurodegenerative diseases (nd). a good in vitro nd model should provide appropriate morphological and molecular features that mimic nd conditions where it can be used to screen potential properties of natural products in addition to unravelling the molecular mechanisms of nd.  in this mini review, we intend to demonstrate two prospective stem cell lines as the potential cell source for in vitro nd model and compare them to the commonly used cells.  the common source of cells that have been used as the in vitro nd models is discussed before going into details talking about the two prospective stem cell lines Show More ... ... Show Less

  • In Vitro
  • Stem Cell Lines
  • Natural Products
Commercial Wireless Versus Standard Stationary EEG Systems For Personalized Emotional Brain-Computer Interfaces: A Preliminary Reliability Check

we present a preliminary data-based assessment of measurement reliability of the commercial 14-electrode emotiv epoctm eeg wireless system in distinguishing between electrophysiological states of emotional function, as compared to a standard research-lab stationary 32-electrode eeg system for personalized single-individual use.  individual observers completed two tasks designed to elicit neural changes in emotional arousal and valence while simultaneously recording their eegs with both systems in separate sessions. participants observed emotion-laden words from the anew database and images from the iaps database, both widely used and validated databases for emotional processes in multidisciplinary research. the pattern of results distinguished between high and low arousal and valence states using the stationary traditional system, but not the commercial device. also, the latter device recorded eeg band frequencies at a much lower resolution and frequency range than the standard system. these findings suggest poor validity when using the commercial device and therefore should be cautioned against in a research setting Show More ... ... Show Less

  • Commercial Device
  • Arousal And Valence
  • Emotional Processes
  • Valence States
  • Reliability Check
WAG/Rij Rat Model: A Resource For The Pharmacology Of Epileptogenesis And Related Neurological/Psychiatric Comorbidities

the discovery of potential antiseizure drugs (asds) requires the use of experimental models that can also provide a unique chance for identifying new effective molecules able to prevent and/or cure epilepsy. most of the preclinical knowledge on epileptogenesis derives from studies performed on post-insult models that are characterized by a recognizable first insult, a silent period lasting until the onset of the first seizure and a chronic period characterized by spontaneous recurrent seizures (srss). at odds, genetic models, in which the first insult remains to be identified, have been poorly investigated. among the genetic models, the wag/rij rat was validated as a suitable experimental model of absence epileptogenesis with neuropsychiatric symptomatology, in which, according to our previous hypothesis on srss onset, genes could be considered the first ‘insult’ underlying all plastic modifications supporting the occurrences of absence seizures in this strain. in fact, in several genetic models, the initial insult could be described as the mutation leading to epilepsy that, to date, remains to be defined in this strain. the silent period ends at the occurrence of the first srs, which is approximately at 2-3 months of age in these rats and after that time the chronic phase initiates, in which, absence seizures increase over time underlying likely further epileptogenic processes. in this review, we describe both the features of this experimental model and the effects of several pharmacological treatments against epileptogenesis and its related comorbidities including depressive-like symptoms and cognitive decline Show More ... ... Show Less

  • Genetic Models
  • Experimental Model
  • Silent Period
  • Absence Seizures
  • Over Time
Challenges And Future Perspectives For 3D Cerebral Organoids As A Model For Complex Brain Disorders

the human brain is made up of billions of neurons and glial cells which are interconnected and organized into specific patterns of neural circuitry, and hence is arguably the most sophisticated organ in human, both structurally and functionally. studying the underlying mechanisms responsible for neurological or neurodegenerative disorders and the developmental basis of complex brain diseases such as autism, schizophrenia, bipolar disorder, alzheimer’s and parkinson’s disease has proven challenging due to practical and ethical limitations on experiments with human material and the limitations of existing biological/animal models. recently, cerebral organoids have been proposed as a promising and revolutionary model for understanding complex brain disorders and preclinical drug screening Show More ... ... Show Less

  • Brain Disorders
  • Bipolar Disorder
  • Animal Models
  • Human Brain
  • Glial Cells
Malaysian Society Of Neurosciences (MSN) – Asian And Oceanian Myology Centre (AOMC) Annual Scientific Meeting 2018

the conjoint 17th asian and oceanian myology centre (aomc) and 28th malaysian society of neurosciences (msn) annual scientific meeting, held in hotel istana, kuala lumpur, malaysia from 27 to 29 july 2018, was a great success to gather all neurosciences professionals locally and in the asian-oceanian region to share the latest updates in neurology and specifically myology. this congress attracted 516 local participants and 167 international delegates from 14 countries.  Show More ... ... Show Less

  • Annual Scientific Meeting
  • Great Success
  • Kuala Lumpur
Pathogenic Mutations In ARX, CDKL5 And STXBP1 Genes Are Not Associated With The Early-Onset Epileptic Encephalopathy In Malaysian Pediatric Patients: A Pilot Study

gene mutation is one of the etiologies of early-onset epileptic encephalopathy (eoee), an age-dependent seizure in infants, which leads to brain defects. previous studies have shown that several genes namely, aristaless-related homeobox (arx), cyclin-dependent kinase-like 5 (cdkl5) and syntaxin-binding protein 1 (stxbp1) are responsible for the pathophysiology of the syndrome. the study involved 20 eoee patients and 60 control subjects, which aimed to investigate the clinical association of malaysian eoee subjects with 13 known pathogenic mutations in the genes of interest. in addition, the entire arx exonic region was also sequenced for known and novel mutations. pcr specificity and efficiency were optimized using conventional pcr and high resolution melting analysis (hrma). all cases and approximately 10% of control amplicon samples were purified and subjected to dna sequencing. all known mutations reported previously were not found in control subjects and malaysian eoee patients with 100% confirmation by sequencing results. sequencing of arx exonic regions of patient samples did not find any mutation in all exons. the preliminary study indicates that selected known pathogenic mutations of arx, cdkl5 and stxbp1 are not associated with eoee in malaysian paediatric patients Show More ... ... Show Less

  • Pathogenic Mutations
  • Early Onset
  • Epileptic Encephalopathy
  • Control Subjects
  • Preliminary Study
Post Spinal Meningitis With Subdural Collection: An Uncommon Complication After Spinal Anaesthesia For Caesarean Section

meningitis after spinal anaesthesia is a rare yet devastating complication of spinal anaesthesia. the exact incidence is unknown. our patient developed signs and symptoms of meningitis 48 hours after spinal anaesthesia and required intensive care unit admission. her cerebrospinal fluid was sterile. computed tomography of brain showed left subdural collection. she recovered well after 6 weeks of intravenous antibiotics. no neurological sequela noted from subsequent follow-up examinations. our case provides an important insight of meningitis with subdural collection after spinal anaesthesia for emergency caesarean section Show More ... ... Show Less

  • Spinal Anaesthesia
  • Subdural Collection
  • Caesarean Section
  • Computed Tomography
  • Intensive Care Unit
Ultrastructural Study Of Sciatic Nerve In Ts1cje Mouse Model For Down Syndrome: An Implication Of Peripheral Nerve Defects In Hypotonia

trisomy 21 is chromosomal abnormality that occurs as a result of triplication of human chromosome 21 (hsa21), a condition also known as down syndrome (ds). beside the intellectual disability and systems anomalies, motor dysfunction due to hypotonia has also been characterised in individuals with ds and yet, its aetiology remains unclear. ts1cje, a mouse model for ds, has a partial trisomy (mmu16) homology to hsa21, is widely used for ds research. this study investigated the morphological changes and degree of myelination in sciatic nerves of the ts1cje mice using both light and transmission electron microscopes processed images. the result showed no morphological difference in the sciatic nerve between the ts1cje and wt mice. the g ratio of the ts1cje mice was significantly (p<0.0001) higher compared to that of the wt mice. two factors are known to determine the g ratio, the axonal diameter and the myeline thickness. there was no significant (p=0.2146) difference in the axonal diameter between the two genotypes. interestingly, the myeline thickness was significantly (p<0.0001) thinner in nerve fibres of the ts1cje mice as compared to that of the wt mice. it is therefore concluded that, the hypomyelination in ts1cje mice may affect the conduction velocity which in turn affect their motor activity Show More ... ... Show Less

  • Down Syndrome
  • Sciatic Nerve
  • Mouse Model
  • Axonal Diameter
  • G Ratio
Epilepsy And Comorbidities: Towards Unraveling The Common Underlying Mechanisms

epilepsy is a chronic neurological disorder characterized by the rapid occurrence of epileptic seizures affecting approximately 70 million people worldwide. the quality of life of people with epilepsy (pwe) is challenged by a series of comorbidities that might include neurologic and neuropsychiatric disorders (cognitive decline, depression, anxiety, schizophrenia, and autism) as well as metabolic, cardiovascular and respiratory diseases. neurobehavioral and other comorbidities might share a reciprocal and complex relationship with epileptogenesis and ictogenesis thus biomarkers of the former might be useful for the prediction of the latter and vice versa. this bidirectional relationship between epilepsy and associated comorbidities has attracted significant attention in recent years as supported by data showing that one half of pwe demonstrate cognitive impairments, 30-50% depressive behavior, 10-25% anxiety disorders and 5-40% autism or autism spectrum disorder (asd). in the past decades, epilepsy-related neurobehavioral comorbidities have been critically discussed, but the current need in unraveling the precise mechanism associated with epilepsy and these neurobehavioral comorbidities is unmet. the precise understanding of the mechanistic pathway underlying these epilepsy-associated comorbid conditions could be instrumental in developing therapeutic interventions that might modify seizure burden and accompanying comorbid conditions Show More ... ... Show Less

  • Comorbid Conditions
  • Quality Of Life
  • Autism Spectrum Disorder
  • The Common
  • Significant Attention
Cholinergic Modulation Of Hippocampal Long-Term Potentiation In Chronic Cerebral Hypoperfused Rats

vascular dementia (vad) is one of the most common types of dementia in alzheimer’s disease (ad). two-vessel occlusion (2vo), also known as permanent bilateral occlusion of the common carotid arteries, induces chronic cerebral hypoperfusion (cch) in rats, resulting in neuronal loss and inflammation (particularly in the cortex and hippocampus).  the 2vo rat model has been widely used to represent vad conditions similar to those seen in humans. synaptic plasticity or long-term potentiation (ltp) is one of the most important neurochemical foundations in learning and memory, deficits of which occur as a result of vad. the aim of this study is to evaluate the role of cholinergic transmission in ltp impairment of cch rat model. there is a significant impairment of ltp following the induction of 2vo surgery (p < .05). treatment with oxotremorine and tacrine cause significant enhancement of ltp and potentiation levels (p < .05). there are also significant effects of paired-pulse facilitations when treated with cholinergic agonists and baseline synaptic transmission with increasing stimulation intensity (p < .0001). ache activity was only found to increase significantly in the hippocampal region (p < .05). the role of cholinergic neurotransmission has been clearly demonstrated in ltp impairment of the cch rat model. augmentation of synaptic transmission was clearly observed in this model via changes of basal synaptic transmission and neurotransmitter release presynaptically Show More ... ... Show Less

  • Synaptic Transmission
  • Rat Model
  • Long Term Potentiation
Transcriptomic Profiling Of Skeletal Muscle From The Ts1cje Mouse Model Of Down Syndrome Suggests Dysregulation Of Trisomic Genes Associated With Neuromuscular Junction Signaling, Oxidative Stress And Chronic Inflammation

ts1cje is a mouse model of down syndrome (ds) with partial triplication of chromosome 16, which encompasses a high number of human chromosome 21 (hsa21) orthologous genes. the mouse model exhibits muscle weakness resembling hypotonia in ds individuals. the effect of extra gene dosages on muscle weakness or hypotonia in ts1cje and ds individuals remains unknown. to identify molecular dysregulation of the skeletal muscle, we compared the transcriptomic signatures of soleus and extensor digitorum longus (edl) muscles between the adult ts1cje and disomic littermates. a total of 166 and 262 differentially expressed protein-coding genes (degs) were identified in the soleus and edl muscles, respectively. the partial trisomy of mmu16 in ts1cje mice has a greater effect on gene expression in edl. top-down clustering analysis of all degs for represented functional ontologies revealed 5 functional clusters in soleus associated with signal transduction, development of reproductive system, nucleic acid biosynthesis, protein modification and metabolism as well as regulation of gene expression. on the other hand, only 3 functional clusters were observed for edl namely neuron and cell development, protein modification and metabolic processes as well as ion transport. a total of 11 selected degs were validated using qpcr (disomic degs: mansc1; trisomic degs: itsn1, rcan1, synj1, donson, dyrk1a, ifnar1, ifnar2, runx1, sod1 and tmem50b). the validated degs were implicated in neuromuscular junction signalling (itsn1, syn1), oxidative stress (sod1, runx1) and chronic inflammation processes (runx1, rcan1, ifnar1, ifnar2). other validated degs have not been well-documented as involved in the skeletal muscle development or function, thus serve as interesting novel candidates for future investigations. to our knowledge, the study was the first attempt to determine the transcriptomic profiles of both soleus and edl muscles in ts1cje mice. it provides new insights on the possible disrupted molecular pathways associated with hypotonia in ds individuals Show More ... ... Show Less

  • Skeletal Muscle
  • Mouse Model
  • Oxidative Stress
  • Gene Expression
  • Down Syndrome
Genetic Association Study Of PDLIM5 And HTR2A Variants In Malaysian Subjects Diagnosed With Bipolar Disorder; A Genetic Modelling Approach

genetic hereditary has been implicated in bipolar disorder pathogenesis. the pdlim5 and htr2a genes have been investigated for its association with bipolar disorder in various populations, however, the results have been conflicting. in this study, we investigate the association between bipolar disorder and the two genes of interest, pdlim5 and htr2a genes. we recruited 253 bipolar disorder patients (75 malays, 104 chinese, and 74 indians) and 505 control individuals (198 malays, 155 chinese, and 152 indians) from three ethnic groups within malaysian population. we genotyped for 3 snps of the pdlim5 (rs2433320, rs2433322 and rs2438146) and 3 snps of the htr2a (rs6313, rs2070040 and rs6311). significant associations between bipolar disorder and each of the 3 snps of pdlim5 in malays, indians and pooled samples. however, only rs2438146 remains significant in the malays as co-dominant (t/t vs. c/c, p=0.004, or=0.128, 95%ci=0.031-0.524) and recessive genetic models (t/t vs. c/t+c/c, p=0.003, or=0.122, 95%ci=0.030-0.494) after applying conservative bonferroni correction. haplotype analysis of 3 snps of pdlim5 also showed a significant association with bipolar disorder. no association was observed between bipolar disorder and each of the 3 snps of htr2a in any of the ethnicities. we conclude that pdlim5 polymorphisms are associated with bipolar disorder in the pooled analysis. after stratification to different ethnic groups, the association remains significant in the malay and indian groups. the association is also supported by the significant association in haplotype analysis of pdlim5. we also conclude there is no association between the htr2a polymorphisms in the malaysian population Show More ... ... Show Less

  • Bipolar Disorder
  • Ethnic Groups
  • Haplotype Analysis
  • Malaysian Population
  • Modelling Approach
Cellular Function Of Satellite Cells Does Not Play A Role In Muscle Weakness Of Adult Ts1cje Mice

down syndrome (ds) is a genetic condition resulting from triplication of human chromosome (hsa)21. besides intellectual disability, ds is frequently associated with hypotonia. satellite cells are the resident cells that provides robust and remarkable regenerative capacity to the skeletal muscles, and its population size has been reported to be disease-associated.  however, little is known about the population size of satellite cells in ds and the association of its intrinsic cellular functionality and hypotonia seen in ds. here, we studied the ts1cje mouse, a ds murine model displays the muscle weakness characteristic. satellite cell populations were immunostained with pax7 and myonuclei numbers in the ts1cje extensor digitorum longus muscle were assessed. their cellular function was further determined via in vitro assay in high-serum conditioned medium. subsequently, the in vitro self-renewal, proliferative, and differentiation activities of these myogenic precursor cells were assessed after 24, 48, and 72h using pax7, myod, and ki67 immunomarkers. our results showed that the population and functionality of ts1cje satellite cell did not differ significantly when compared to the wildtype cells isolated from disomic littermates. in conclusion, our findings indicate that intrinsic cellular functionality of the satellite cells, do not contribute to muscle weakness in ts1cje mouse Show More ... ... Show Less

  • Satellite Cells
  • Muscle Weakness
  • In Vitro
  • Population Size
Free Open Access To Liberate And Unleash Neglected Science

open access has become a choice for scientific publication. in many countries, open access publication has been made compulsory for publicly funded studies. since 2013, government-funded research paper in united states must be made freely available within 12 months of publication. such policy will ensure maximum accessibility and circulation of published articles. while the scientific community is benefited at large due to free access and distribution of published materials, open access publication is never free due to the various costs involved in the production, permanent archival and digitalisation of scholarly articles Show More ... ... Show Less

  • Open Access Publication
  • United States
  • Scientific Community
  • Publicly Funded