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Neuroscience Research Notes, Volume 3, pp 9-26; doi:10.31117/neuroscirn.v3i3.50
Brain-derived neurotrophic factor (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 aetiology of the neuropsychiatric illnesses have 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. Val allele has been found associated with these disorders, whereas some studies reported the involvement of the Met allele, and some reported no association at all. Similarly, the association of the BDNF variant with the BDNF level remains controversial. It is, therefore, essential to conduct more studies with larger sample sizes and look at the haplotype level to determine the association.
Neuroscience Research Notes, Volume 3, pp 1-8; doi:10.31117/neuroscirn.v3i3.51
Neuroscience has emerged as a richly transdisciplinary field, poised to leverage potential synergies with information technology. To investigate the complex nervous system in its normal function and the disease state, researchers in the field are increasingly reliant on generating, sharing and analyzing diverse data from multiple experimental paradigms at multiple spatial and temporal scales. There is growing recognition that brain function must be investigated from a systems perspective. This requires an integrated analysis of genomic, proteomic, anatomical, functional, topological and behavioural information to arrive at accurate scientific conclusions. The integrative neuroinformatics approaches for exploring complex structure-function relationships in the nervous system have been extensively reviewed. To support neuroscience research, the neuroscientific community also generates and maintains web-accessible databases of experimental and computational data and innovative software tools. Neuroinformatics is an emerging sub-field of neuroscience which focuses on addressing the unique technological and computational challenges to integrate and analyze the increasingly high-volume, multi-dimensional, and fine-grain data generated from neuroscience experiments. The most visible contributions from neuroinformatics include the myriad reference atlases of brain anatomy (human and other mammals such as rodents, primates and pig), gene and protein sequences and the bioinformatics software tools for alignment, matching and identification. Other neuroinformatics initiatives include the various open-source preprocessing and processing software and workflows for data analysis as well as the specifications for data format and software interoperability that allow seamless exchange of data between labs, software tools and modalities.
Neuroscience Research Notes, Volume 3, pp 15-22; doi:10.31117/neuroscirn.v3i2.48
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.
Neuroscience Research Notes, Volume 3, pp 4-14; doi:10.31117/neuroscirn.v3i2.49
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.
Neuroscience Research Notes; doi:10.31117/neuroscirn
Neuroscience Research Notes, Volume 3, pp 1-3; doi:10.31117/neuroscirn.v3i2.46
Neuroscience Research Notes, Volume 3, pp 32-33; doi:10.31117/neuroscirn.v3i1.45
This corrects the article https://doi.org/10.31117/neuroscirn.v2i3.35.
Neuroscience Research Notes, Volume 3, pp 24-31; doi:10.31117/neuroscirn.v3i1.41
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.
Neuroscience Research Notes, Volume 3, pp 11-23; doi:10.31117/neuroscirn.v3i1.39
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.
Neuroscience Research Notes, Volume 3, pp 1-10; doi:10.31117/neuroscirn.v3i1.40
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.