Neuroscience Research Notes

Single nucleotide polymorphism of BDNF Val66Met (rs6265) and its association to neuropsychiatric disorders

2020-05-18T17:44:56+08:00

BDNF is the most abundant neurotrophin in the central nervous system and was shown to be involved in neuronal growth, differentiation, and synaptic plasticity. A single nucleotide polymorphism at the pro-region of the BDNF gene (rs6265) has been reported to alter the amino acid from valine to methionine at codon 66 and was associated with neuropsychiatric disorders in several studies. To date, the results on the association of BDNF rs6265 to the etiology of the neuropsychiatric illnesses has been inconsistent with some studies reporting a positive association and others reporting no association. Concerning the past inconsistent reports, this mini-review aims at determining the association of BDNF rs6265 and neuropsychiatric disorders among the different studies. Firstly, we discuss the findings on studies reporting the association of BDNF rs6265 with depression whereby a positive association between the BDNF variant and depression was obtained in several studies on the Caucasian, German, Chinese, and Malaysian population but not in studies on the Korean and other populations. Likewise, some studies found the occurrence of the SNP to be associated with a reduction in the BDNF level in depressed cases, but others found no effect at all. We then reported findings on the association of BDNF rs6265 with anxiety disorder, post-traumatic stress disorder, obsessive-compulsive disorder, panic disorder, bipolar disorder, and schizophrenia. Some of these studies reported the Val allele to be involved with the disorder, whereas the others reported a role of the Met allele in the disorder, and others reported no association at all. Similarly, some studies found an association of the BDNF variant with the BDNF level, but others did not. It is, therefore, essential to conduct more studies with larger sample sizes and look at the haplotype level to determine the association.

Improved β-catenin detection in spinal cord tissue sections: autofluorescence quenching

2020-04-28T05:45:18+08:00

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.

Brain network interventions may break cycle of drug addiction relapse

2020-05-11T21:23:00+08:00

In Malaysia, drug abstinence-centric programs failed to reduce drug use. 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. Despite this success, MMT retention rates remain low, as methadone is only able to stall the consumption of drugs, but not stop it completely. Furthermore, neuroimaging research revealed that addicts enrolled in MMT still display addict-like traits, including sensitivity to drug cues, craving and withdrawal, in spite of treatment adherence. Brain activity amongst treated addicts continues to bear similarities to untreated addicts, 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 the largely ignored problem of relapse in the life-time rehabilitation cycle of drug addicts. 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, this approach should finally break the cycle of addiction.

COVID-19: An Update on Research and Development

2020-03-29T07:12:23+08:00

As of March, most of the world is under the order of a “lockdown” or “restricted movement control” whereby world leaders and medical experts believe that social isolation is the best option at reducing the spread of the highly infectious and novel disease, that is Coronavirus Disease (COVID-19). While this preventive measure is in place, various diagnostic kits and treatment strategies are being researched daily to diagnose and curb this disease quickly. This mini-review summarizes the characteristics of the SARS-CoV-2 virus and evaluates the diagnostic kits and treatment drugs as well as vaccines that are either currently being used (RT-PCR) or in the clinical pipeline for safety and efficacy testing, respectively. The sooner efficient diagnosis and treatment can be made, the greater the number of lives will be saved.

COVID-19 and mental health: Our reactions to its actions

2020-03-29T21:13:26+08:00

The genetic epidemiology suggests that coronavirus disease 2019 (COVID-19) is most likely transmitted to the human population in November or December 2019, originating from Wuhan and spread entirely by human-to-human transmission. The period of the Chinese New Year holidays is thought to be one of the key periods where a substantial transmission took place within Wuhan. Moreover, the movement of people from Wuhan resulted in massive spread nationally and internationally when people traveled during the holidays.

Corrigendum: Genotypic and phenotypic variation of CADASIL among Chinese, Indians and Rungus in Malaysia

2020-03-17T02:31:29+08:00

This corrects the article https://doi.org/10.31117/neuroscirn.v2i3.35.

Research beyond biomedical confines: towards better mental health and well-being for all

2019-11-19T05:51:44+08:00

‘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.

Brain Tissue Contrast: CT versus MRI

2019-11-27T21:22:54+08:00

To differentiate different soft tissues of the brain, the imaging modality should display the tissues with excellent contrast. Contrast is defined as the separation between the darkest and brightest areas of the image. All imaging modalities do not represent the brain tissues with same level of contrast. It is important to evaluate what level of contrast is provided by CT and MRI ,and how human eye perceives these images. Human eye can identify an object in relation to its immediate background. The visual ability to recognize an object is determined by this ability rather than overall features of the total image. CT can provide better image contrast only when there is greater difference between dark and light areas of the image. In CT, tissues with similar density are not displayed with better contrast comparing to MRI. Hence, differentiating grey and white matter is difficult with CT comparing to MRI. In CT, principle source of contrast is provided by differences in physical density whereas, in MRI several sources provide contrast.

MTRR gene variant rs1801394 found in Malaysian patients with neural tube defects

2020-03-08T13:33:56+08:00

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.

sLORETA neurofeedback in fibromyalgia

2020-01-29T18:32:20+08:00

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.

Moral judgments in obsessive-compulsive disorder: a narrative mini-review

2020-02-19T11:30:28+08:00

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.

Antioxidant properties of yttrium oxide nanoparticles: a potential treatment for Alzheimer’s disease

2019-11-05T22:06:32+08:00

Alzheimer’s disease (AD) is a fatal neurodegenerative disease that requires immediate attention. Oxidative stress that lead to generation of reactive oxygen species is a contributing factor to the disease progression by promoting synthesis and deposition of amyloid-β, the main hallmark protein in AD. It has been previously demonstrated that yttrium oxide (Y₂O₃) nanoparticles possess antioxidant properties and can alleviate cellular oxidative injury in diabetic models. It is likely that Y₂O₃ nanoparticles can also be used for the treatment of AD.

Dopamine transporter 1 (DAT1) rs40184 single nucleotide polymorphism is not associated with the Malaysian major depressive disorder subjects

2019-12-05T13:20:29+08:00

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.

Genotypic and phenotypic variation of CADASIL among Chinese, Indians and Rungus in Malaysia

2020-03-16T23:04:32+08:00

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.553T>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 multi-ethnic 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.

Zinc transporter-3 [SLC30A3 (rs11126936)] polymorphism is associated with major depressive disorder in Asian subjects

2019-09-15T07:15:36+08:00

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.

Seizure disorder in ground squirrels

2019-05-22T21:07:31+08:00

The antelope ground squirrel may be a new useful animal model for the study of epilepsy. It is reported here that, in a laboratory colony of 50 individuals born to wild-caught pregnant females, 10 squirrels started exhibiting natural seizures at 10 months of age. The seizures were evoked simply by exposure to an unfamiliar environment (cage change) and re-occurred many times. Further investigation may clarify whether these seizures are analogous to the seizures of human epilepsy.

The potential of MLC901 (NeuroAiD II™), a traditional Chinese medicine

2019-06-18T19:25:30+08:00

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.

Chemical hypoxia in human pluripotent NT2 stem cell-derived neurons: Effect of hydroxamic acid and benzamide-based epigenetic drugs

2019-08-23T11:44:15+08:00

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.

An update on HLA alleles as pharmacogenetic markers for antiepileptic drug-induced cutaneous adverse reaction

2019-06-18T19:25:53+08:00

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.

Challenges and future perspectives for 3D cerebral organoids as a model for complex brain disorders

2019-06-18T19:27:40+08:00

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.

The treatment of epileptic seizures: the potential of Malaysian medicinal plants

2019-06-18T19:26:36+08:00

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.

Prospective stem cell lines as in vitro neurodegenerative disease models for natural product research

2019-11-11T05:46:32+08:00

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.

Neuroprotective effects of ethanolic extract of Orthosiphon stamineus in an in-vitro model

2019-03-23T08:17:57+08:00

Alzheimer disease (AD) are one of the most common types of dementia, which is characterized by chronic and progressive neurodegeneration that triggers, advanced cognitive impairment. In recent times, there has been a growing interest in using complimentary therapy and phytochemicals from medicinal herbs to enhance the quality of life and prevent therapy induced side-effects, particularly in using phytochemicals from medicinal herbs as they possess anti-inflammatory and antioxidant activities that may potentially hinder neurodegeneration and improve memory and cognitive functioning. In this study, the in vitro neuroprotective activity of the Orthosiphon stamineus extract was investigated via inhibition of acetylcholinesterase (AChE) enzyme as well as rosmarinic acid, a major flavonoid component of O. stamineus extract. Additionally, the in-vitro evaluation of neurotoxicity & neuroprotective property of O. stamineus standardized extract was further evaluated using SH-SY5Y human neuroblastoma cell that was challenged with β-amyloid, a key component in Alzheimer’s disease. Based on the results attained from the AChE enzyme inhibition activity, both O. stamineus and Rosmarinic acid are found to be potent AChE inhibitors with an IC50 value of 3.13mg/ml and 0.164 mg/ml respectively. O. stamineus extract was also found to be neuroprotective when challenged with β-amyloid. Thus, present study further validated the use of O. stamineus plant extract as a strong candidate for the development of potential therapeutic target for the treatment of neurodegenerative diseases like Alzheimer’s disease.

Malaysian Society of Neurosciences (MSN) – Asian and Oceanian Myology Centre (AOMC) Annual Scientific Meeting 2018

2019-06-18T19:28:02+08:00

The conjoint 17^th Asian and Oceanian Myology Centre (AOMC) and 28^th 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.

WAG/Rij rat model: a resource for the pharmacology of epileptogenesis and related neurological/psychiatric comorbidities

2019-06-18T19:27:19+08:00

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.

Commercial wireless versus standard stationary EEG systems for personalized emotional brain-computer interfaces: a preliminary reliability check

2019-06-18T19:26:58+08:00

We present a preliminary data-based assessment of measurement reliability of the commercial 14-electrode Emotiv EPOC^TM 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.

Epilepsy and Comorbidities: Towards unraveling the common underlying mechanisms

2019-06-18T19:29:27+08:00

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.

Post spinal meningitis with subdural collection: an uncommon complication after spinal anaesthesia for caesarean section

2019-06-18T19:28:44+08:00

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.

Ultrastructural study of sciatic nerve in Ts1Cje mouse model for Down syndrome: an implication of peripheral nerve defects in hypotonia

2019-06-18T19:29:06+08:00

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.

Pathogenic mutations in ARX, CDKL5 and STXBP1 genes are not associated with the early-onset epileptic encephalopathy in Malaysian pediatric patients: A pilot study

2019-06-18T19:28:24+08:00

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.

Cholinergic modulation of hippocampal long-term potentiation in chronic cerebral hypoperfused rats

2019-06-18T19:29:49+08:00

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.

A systematic review of randomised controlled trials examining Curcuma longa for dementia

2018-07-05T11:58:36+08:00

Curcuma longa has been used to treat several ailments traditionally, such as rheumatoid arthritis, conjunctivitis, skin cancer, small pox, chicken pox, wound healing, urinary tract infections and liver ailments. Due to its therapeutic properties, it has recently grown in popularity as a potential adjunct therapy for dementia. However, no systematic review of randomised controlled trials has been conducted to evaluate its efficacy and safety for cognitive decline. In this dissertation, literature searches were conducted using four electronic databases, including PubMed Central, Science Direct, CINAHL, and PsycINFO. We retrieved five published studies which were randomised control trials and have included these in the review. Search terms used were ‘dementia’, ‘Alzheimer*’, ‘ageing’, ‘mild cognitive impairment’, ‘cognitive decline’, ‘turmeric’ and ‘curcuma longa’. Efficacy measures such as biochemical markers, neuropsychological assessments, and pharmacological measures have been extracted from studies and synthesised in the review. Although several in vitro and in vivo model studies have found neuroprotective effects of curcumin in Alzheimer’s disease, there is not sufficient evidence to support curcumin use in humans with Alzheimer’s disease, and healthy volunteers. Short term usage of curcumin has been found to be safe. Various reasons such as its low bioavailability and inconsistency in study designs were responsible for discrepancies between preclinical findings and human trials.

The discrepancies on human hippocampal neurogenesis throughout aging

2018-07-16T11:13:29+08:00

Generation of new neuron is derived from subgranular zone of dentate gyrus of the adult mammalian hippocampus. In vivo studies showed a conflict finding regarding the age-related changes in specific hippocampus region. Some studies speculated that the hippocampus volume was decline and the shape was changing toward aging. Meanwhile, other studies found that the volume of hippocampus did not change across ages. Due to this discrepancies, two different studies (publish recently) provide an evidence on the human hippocampal neurogenesis throughout aging. However, these studies have shown a conflict of findings from generation of progenitor cell and neuron from subgranular zone throughout the aging. Sorrells et al (2018) indicates that the number of proliferative cell and neuron was sharply decline from gestational period through aging in hippocampus. This finding was contrary with Boldrini et al (2018) where number of proliferative cell and neuron were sustaining from between 20 to 80 years old. Analysis made was based on quantitative analysis on immunohistochemistry slide that was observed under confocal microscope. The difference between these studies was the approaches they used to analyse the data. One study used area in mm² to quantitate the total number of positive cell while the other study used stereology method. The stereology is a gold standard to analyse a total cell density which provide approximately a total number of cell. Thus, the different ways of data analyses will provide different outcomes.

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

2019-06-19T19:36:58+08:00

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.

A three-dimensional hydrogel culture for primary microglia activation

2018-10-30T19:51:07+08:00

The conventional monolayer culture of cells does not mimic the mechanical state of cells within tissue. Cell culture is a great tool for the study of microglial responses, and we have previously described a three dimensional (3D) collagen hydrogel for the culture and stimulation of BV2 microglia. Here we report preliminary data of primary microglia cultured in 3D collagen gels and stimulated with lipopolysaccharide (LPS) and interferon gamma (IFN-g). Stimulated cultures exhibited profound NO production, up to 39.37 ± 9.53 µM NO at 72 hours compared to a negligible 0.95 ± 0.58 µM in unstimulated cultures. Also, the percentage of CD40⁺ cells increased to 90.9% in stimulated cultures compared to 39.3% in untreated cultures. These demonstrate that primary microglia can be stimulated within 3D collagen gel cultures. Importantly, primary microglia remained viable in 3D culture at 72 hours after stimulation.

Genetic association study of PDLIM5 and HTR2A variants in Malaysian subjects diagnosed with bipolar disorder; a genetic modelling approach

2019-06-19T19:37:19+08:00

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.

A systematic review of randomised controlled trials examining Curcuma longa for dementia

2018-04-22T02:05:37+08:00

Curcuma longa has been used to treat several ailments traditionally, such as rheumatoid arthritis, conjunctivitis, skin cancer, small pox, chicken pox, wound healing, urinary tract infections and liver ailments. Due to its therapeutic properties, it has recently grown in popularity as a potential adjunct therapy for dementia. However, no systematic review of randomised controlled trials has been conducted to evaluate its efficacy and safety for cognitive decline. In this dissertation, literature searches were conducted using four electronic databases, including PubMed Central, Science Direct, CINAHL, and PsycINFO. We retrieved five published studies which were randomised control trials and have included these in the review. Search terms used were ‘dementia’, ‘Alzheimer*’, ‘ageing’, ‘mild cognitive impairment’, ‘cognitive decline’, ‘turmeric’ and ‘curcuma longa’. Efficacy measures such as biochemical markers, neuropsychological assessments, and pharmacological measures have been extracted from studies and synthesised in the review. Although several in vitro and in vivo model studies have found neuroprotective effects of curcumin in Alzheimer’s disease, there is not sufficient evidence to support curcumin use in humans with Alzheimer’s disease, and healthy volunteers. Short term usage of curcumin has been found to be safe. Various reasons such as its low bioavailability and inconsistency in study designs were responsiblefor discrepancies between preclinical findings and human trials.

Cellular function of satellite cells does not play a role in muscle weakness of adult Ts1Cje mice

2019-06-19T19:37:40+08:00

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.

Free open access to liberate and unleash neglected science

2019-06-19T19:38:00+08:00

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.