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Fulltext Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies

Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Electronic address: andrew.mcintosh@ed.ac.uk, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Cell, 2025 Feb 06;188(3):640-652.e9.
PMID: 39814019 DOI: 10.1016/j.cell.2024.12.002

In a genome-wide association study (GWAS) meta-analysis of 688,808 individuals with major depression (MD) and 4,364,225 controls from 29 countries across diverse and admixed ancestries, we identify 697 associations at 635 loci, 293 of which are novel. Using fine-mapping and functional tools, we find 308 high-confidence gene associations and enrichment of postsynaptic density and receptor clustering. A neural cell-type enrichment analysis utilizing single-cell data implicates excitatory, inhibitory, and medium spiny neurons and the involvement of amygdala neurons in both mouse and human single-cell analyses. The associations are enriched for antidepressant targets and provide potential repurposing opportunities. Polygenic scores trained using European or multi-ancestry data predicted MD status across all ancestries, explaining up to 5.8% of MD liability variance in Europeans. These findings advance our global understanding of MD and reveal biological targets that may be used to target and develop pharmacotherapies addressing the unmet need for effective treatment.

Matched MeSH terms: Neurons/drug effects; Neurons/metabolism
The malleable brain: plasticity of neural circuits and behavior - a review from students to students

Schaefer N, Rotermund C, Blumrich EM, Lourenco MV, Joshi P, Hegemann RU, et al.

J Neurochem, 2017 Jun 20.
PMID: 28632905 DOI: 10.1111/jnc.14107

One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation and long-term depression, respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by long-term potentiation and long-term depression, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity. Read the Editorial Highlight for this article on doi: 10.1111/jnc.14102.

Matched MeSH terms: Neurons
Fulltext Data on the Lignosus rhinocerotis water soluble sclerotial extract affecting intracellular calcium level in rat dorsal root ganglion cells

Lee MK, Millns P, Mbaki Y, Ng ST, Tan CS, Lim KH, et al.

Data Brief, 2018 Jun;18:1322-1326.
PMID: 29900310 DOI: 10.1016/j.dib.2018.04.033

The data in this article contain supporting evidence for the research manuscript entitled "Bronchodilator effects of Lignosus rhinocerotis extract on rat isolated airways is linked to the blockage of calcium entry" by Lee et al. (2018) [1]. The data were obtained by calcium imaging technique with fluorescent calcium indicator dyes, Fura 2-AM, to visualize calcium ion movement in the rat dorsal ganglion (DRG) cells. The effects of L. rhinocerotis cold water extract (CWE1) on intracellular calcium levels in the DRG cells were presented.

Matched MeSH terms: Neurons
Human tuberculosis brain promotes neuronal apoptosis but not in astrocytes with high expression of vascular endothelial growth factor

Othman FN, Muthuraju S, Noor SSM, Abdullah S, Mohd Yusoff AA, Tharakan J, et al.

Tuberculosis (Edinb), 2018 09;112:45-51.
PMID: 30205968 DOI: 10.1016/j.tube.2018.07.007

The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0.40). Higher Bcl-2 expression was seen in astrocytes of infected brain tissues compared to the control tissues (p = 0.004) promoted a higher anti-apoptotic activity in astrocytes. The neurons expressed strong Bax expression in the infected brain tissues compared to the control tissues (p 

Matched MeSH terms: Neurons/metabolism*; Neurons/microbiology; Neurons/pathology
Fucosterol exerts protection against amyloid β-induced neurotoxicity, reduces intracellular levels of amyloid β and enhances the mRNA expression of neuroglobin in amyloid β-induced SH-SY5Y cells

Gan SY, Wong LZ, Wong JW, Tan EL

Int J Biol Macromol, 2019 Jan;121:207-213.
PMID: 30300695 DOI: 10.1016/j.ijbiomac.2018.10.021

Alzheimer's disease (AD) is a neurodegenerative disease that leads to progressive loss of neurons which often results in deterioration of memory and cognitive function. The development of AD is highly associated with the formation of senile plaques and neurofibrillary tangles. Amyloid β (Aβ) induces neurotoxicity and contributes to the development of AD. Recent evidences also highlighted the importance of neuroglobin (Ngb) in ameliorating AD. This study assessed the ability of fucosterol, a phytosterol found in brown alga, in protecting SH-SY5Y cells against Aβ-induced neurotoxicity. Its effects on the mRNA levels of APP and Ngb as well as the intracellular Aβ levels were also determined in Aβ-induced SH-SY5Y cells. SH-SY5Y cells were exposed to fucosterol prior to Aβ treatment. The effect on apoptosis was determined using Annexin V FITC staining and mRNA expression was studied using RT-PCR. Flow cytometry confirmed the protective effects of fucosterol on SH-SY5Y cells against Aβ-induced apoptosis. Pretreatment with fucosterol increased the Ngb mRNA levels but reduced the levels of APP mRNA and intracellular Aβ in Aβ-induced SH-SY5Y cells. These observations demonstrated the protective properties of fucosterol against Aβ-induced neurotoxicity in neuronal cells.

Matched MeSH terms: Neurons/cytology; Neurons/drug effects; Neurons/metabolism
Fulltext The therapeutic potential of stem cells and progenitor cells for the treatment of Parkinson's disease

Liau MT, Amini F, Ramasamy TS

Tissue Eng Regen Med, 2016 Oct;13(5):455-464.
PMID: 30603427 DOI: 10.1007/s13770-016-9093-2

Parkinson's disease (PD) is the second most common neurodegenerative disorder. It is usually seen in those above 50 years old. Current medical treatments only provide symptomatic relief but cannot cure the disease. There are claims that PD can be cured by stem cell transplant. The present study is aimed to assess the clinical potency and safety of stem cell in treating PD. A total of eleven articles were included for analysis, with four randomised control trials (RCTs), five non-RCTs and 2 follow up studies. All the four non-RCTs showed improvement of Unified Parkinson's Disease Rating Scale with no adverse events. However, results from RCTs showed no significant differences in the rating score among the transplant group and the Sham surgery group. The secondary analysis of one study showed a significant improvement of the rating score in those patients aged 60 and younger. Transplant group also associated with an overall higher incidence of adverse events. In conclusion, the RCTs and non-RCTs produced opposite results. When the studies were performed as non-RCTs in small number of patients, they showed promising result in the patients. It could say that currently the use of stem cell/progenitor cells in treating PD need much research despite having the implanted stem cell to be able to survive and integrated. The survival of implanted dopamine neurons in the striatum, however, does not indicate a success in correcting PD symptoms. Further investigations will shed light on the application and mechanism of action of stem cells in treating PD.
Electronic Supplementary Material: Supplementary material is available for this article at 10.1007/s13770-016-9093-2 and is accessible for authorized users.

Matched MeSH terms: Dopaminergic Neurons
The adsorptive removal of As (III) using biomass of arsenic resistant Bacillus thuringiensis strain WS3: Characteristics and modelling studies

Altowayti WAH, Algaifi HA, Bakar SA, Shahir S

Ecotoxicol Environ Saf, 2019 May 15;172:176-185.
PMID: 30708229 DOI: 10.1016/j.ecoenv.2019.01.067

Globally, the contamination of water with arsenic is a serious health issue. Recently, several researches have endorsed the efficiency of biomass to remove As (III) via adsorption process, which is distinguished by its low cost and easy technique in comparison with conventional solutions. In the present work, biomass was prepared from indigenous Bacillus thuringiensis strain WS3 and was evaluated to remove As (III) from aqueous solution under different contact time, temperature, pH, As (III) concentrations and adsorbent dosages, both experimentally and theoretically. Subsequently, optimal conditions for As (III) removal were found; 6 (ppm) As (III) concentration at 37 °C, pH 7, six hours of contact time and 0.50 mg/ml of biomass dosage. The maximal As (III) loading capacity was determined as 10.94 mg/g. The equilibrium adsorption was simulated via the Langmuir isotherm model, which provided a better fitting than the Freundlich model. In addition, FESEM-EDX showed a significant change in the morphological characteristic of the biomass following As (III) adsorption. 128 batch experimental data were taken into account to create an artificial neural network (ANN) model that mimicked the human brain function. 5-7-1 neurons were in the input, hidden and output layers respectively. The batch data was reserved for training (75%), testing (10%) and validation process (15%). The relationship between the predicted output vector and experimental data offered a high degree of correlation (R2 = 0.9959) and mean squared error (MSE; 0.3462). The predicted output of the proposed model showed a good agreement with the batch work with reasonable accuracy.

Matched MeSH terms: Neurons
U6 snRNA is a suitable endogenous control for microRNA-124 and -134 in cultured rat hippocampal neurons

Azlina Ahmad-Annuar, Ai Sze Ching

Sains Malaysiana, 2015;44:1481-1488.

As researchers seek to determine the cellular mechanisms underlying biological processes, they have turned to analyze the functional role of microRNAs to understand this process in details. Here, we investigated the expression pattern of two microRNAs, miR-124 and -134 in maturing neurons and found that the choice of endogenous controls influenced the observed expression levels of these microRNAs. We have cultured rat hippocampal neurons and performed quantitative PCR on the microRNAs using Taqman gene expression assays. The expression of miRNAs was normalised with selected endogenous controls. Using BestKeeper and NormFinder software, we found that 18S rRNA and 5S rRNA to be unsuitable as endogenous controls in this system, while normalising to U6 snRNA produced more consistent results. Our study would like to highlight the importance of empirically testing proposed endogenous controls in any model system before data interpretation is carried out.

Matched MeSH terms: Neurons
Collinear facilitation and contour integration in autistic adults: Examining lateral and feedback connectivity

Gowen E, Jachim S, Subri S, Dickinson C, Hamblin-Pyke B, Warren PA

Vision Res, 2020 12;177:56-67.
PMID: 32977182 DOI: 10.1016/j.visres.2020.08.004

Alongside difficulties with communication and social interaction, autism is often accompanied by unusual sensory and perceptual experiences including enhanced visual performance on tasks that involve separating local parts from global context. This superiority may be the result of atypical integrative processing, involving feedback and lateral connections between visual neurons. The current study investigated the integrity of these connections in autistic adults by examining two psychophysics tasks that rely on these processes - collinear facilitation and contour integration. The relative contribution of feedback and lateral connectivity was studied by altering the timing of the target relative to the flankers in the collinear facilitation task, in 16 autistic and 16 non-autistic adults. There were no significant differences in facilitation between the autistic and non-autistic groups, indicating that for this task and participant sample, lateral and feedback connectivity appear relatively intact in autistic individuals. Contour integration was examined in a different group of 20 autistic and 18 non-autistic individuals, for open and closed contours to assess the closure effect (improved detection of closed compared to open contours). Autistic individuals showed a reduced closure effect at both short (150 ms) and longer (500 ms) stimulus presentation durations that was driven by better performance of the autistic group for the open contours. These results suggest that reduced closure in a simple contour detection paradigm is unlikely to be due to slower global processing. Reduced closure has implications for understanding sensory overload by contributing to reduced figure-ground segregation of salient visual features.

Matched MeSH terms: Neurons
Implication of HMGB1 signaling pathways in Amyotrophic lateral sclerosis (ALS): From molecular mechanisms to pre-clinical results

Paudel YN, Angelopoulou E, Piperi C, Othman I, Shaikh MF

Pharmacol Res, 2020 06;156:104792.
PMID: 32278047 DOI: 10.1016/j.phrs.2020.104792

Amyotrophic lateral sclerosis (ALS) is a devastating and rapidly progressing neurodegenerative disorder with no effective disease-modifying treatment up to date. The underlying molecular mechanisms of ALS are not yet completely understood. However, the critical role of the innate immune system and neuroinflammation in ALS pathogenesis has gained increased attention. High mobility group box 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, acting as a pro-inflammatory cytokine mainly through activation of its principal receptors, the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4) which are crucial components of the innate immune system. HMGB1 is an endogenous ligand for both RAGE and TLR4 that mediate its biological effects. Herein, on the ground of pre-clinical findings we unravel the underlying mechanisms behind the plausible contribution of HMGB1 and its receptors (RAGE and TLR4) in the ALS pathogenesis. Furthermore, we provide an account of the therapeutic outcomes associated with inhibition/blocking of HMGB1 receptor signalling in preventing motor neuron's death and delaying disease progression in ALS experimental models. There is strong evidence that HMGB1, RAGE and TLR4 signaling axes might present potential targets against ALS, opening a novel headway in ALS research that could plausibly bridge the current treatment gap.

Matched MeSH terms: Motor Neurons/immunology; Motor Neurons/metabolism*; Motor Neurons/pathology
Fulltext Neuroprotective effects of Hericium erinaceus (Bull.: Fr.) Pers. against high-dose corticosterone-induced oxidative stress in PC-12 cells

Lew SY, Lim SH, Lim LW, Wong KH

BMC Complement Med Ther, 2020 Nov 11;20(1):340.
PMID: 33176761 DOI: 10.1186/s12906-020-03132-x

BACKGROUND: Hericium erinaceus is a culinary and medicinal mushroom in Traditional Chinese Medicines. It has numerous pharmacological effects including immunomodulatory, anti-tumour, anti-microbial, anti-aging and stimulation of nerve growth factor (NGF) synthesis, but little is known about its potential role in negating the detrimental effects of oxidative stress in depression. The present study investigated the neuroprotective effects of H. erinaceus standardised aqueous extract (HESAE) against high-dose corticosterone-induced oxidative stress in rat pheochromocytoma (PC-12) cells, a cellular model mimicking depression.
METHODS: PC-12 cells was pre-treated with HESAE for 48 h followed by 400 μM corticosterone for 24 h to induce oxidative stress. Cells in complete medium without any treatment or pre-treated with 3.125 μg/mL desipramine served as the negative and positive controls, respectively. The cell viability, lactate dehydrogenase (LDH) release, endogenous antioxidant enzyme activities, aconitase activity, mitochondrial membrane potentials (MMPs), intracellular reactive oxygen species (ROS) levels and number of apoptotic nuclei were quantified. In addition, HESAE ethanol extract was separated into fractions by chromatographic methods prior to spectroscopic analysis.
RESULTS: We observed that PC-12 cells treated with high-dose corticosterone at 400 μM had decreased cell viability, reduced endogenous antioxidant enzyme activities, disrupted mitochondrial function, and increased oxidative stress and apoptosis. However, pre-treatment with HESAE ranging from 0.25 to 1 mg/mL had increased cell viability, decreased LDH release, enhanced endogenous antioxidant enzyme activities, restored MMP, attenuated intracellular ROS and protected from ROS-mediated apoptosis. The neuroprotective effects could be attributed to significant amounts of adenosine and herierin III isolated from HESAE.
CONCLUSIONS: HESAE demonstrated neuroprotective effects against high-dose corticosterone-induced oxidative stress in an in vitro model mimicking depression. HESAE could be a potential dietary supplement to treat depression.

Matched MeSH terms: Neurons/cytology; Neurons/drug effects*; Neurons/metabolism
Fulltext The Feedback-Related Negativity and the P300 Brain Potential Are Sensitive to Price Expectation Violations in a Virtual Shopping Task

Schaefer A, Buratto LG, Goto N, Brotherhood EV

PLoS One, 2016 09 22;11(9):e0163150.
PMID: 27658301 DOI: 10.1371/journal.pone.0163150

A large body of evidence shows that buying behaviour is strongly determined by consumers' price expectations and the extent to which real prices violate these expectations. Despite the importance of this phenomenon, little is known regarding its neural mechanisms. Here we show that two patterns of electrical brain activity known to index prediction errors-the Feedback-Related Negativity (FRN) and the feedback-related P300 -were sensitive to price offers that were cheaper than participants' expectations. In addition, we also found that FRN amplitude time-locked to price offers predicted whether a product would be subsequently purchased or not, and further analyses suggest that this result was driven by the sensitivity of the FRN to positive price expectation violations. This finding strongly suggests that ensembles of neurons coding positive prediction errors play a critical role in real-life consumer behaviour. Further, these findings indicate that theoretical models based on the notion of prediction error, such as the Reinforcement Learning Theory, can provide a neurobiologically grounded account of consumer behavior.

Matched MeSH terms: Neurons
Fulltext A golden hamster model for human acute Nipah virus infection

Wong KT, Grosjean I, Brisson C, Blanquier B, Fevre-Montange M, Bernard A, et al.

Am J Pathol, 2003 Nov;163(5):2127-37.
PMID: 14578210 DOI: 10.1016/S0002-9440(10)63569-9

A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153-2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection.

Matched MeSH terms: Neurons/pathology; Neurons/ultrastructure; Neurons/virology
Role of microglia in embryonic neurogenesis

Tong CK, Vidyadaran S

Exp Biol Med (Maywood), 2016 Sep;241(15):1669-75.
PMID: 27555616 DOI: 10.1177/1535370216664430

Microglia begin colonizing the developing brain as early as embryonic day 9, prior to the emergence of neurons and other glia. Their ontogeny is also distinct from other central nervous system cells, as they derive from yolk sac hematopoietic progenitors and not neural progenitors. In this review, we feature these unique characteristics of microglia and assess the spatiotemporal similarities between microglia colonization of the central nervous system and embryonic neurogenesis. We also infer to existing evidence for microglia function from embryonic through to postnatal neurodevelopment to postulate roles for microglia in neurogenesis.

Matched MeSH terms: Neurons
Fulltext Model development of microwave remote sensing of sea ice

Lee, Y.J., Yap, H.J., Lim, W.K., Ewe, H.T., Chuah, H.T.

ASM Science Journal, 2009;3(2):131-142.
MyJurnal

Three techniques to retrieve information on sea ice thickness from both active and passive radar backscatter data are presented. The first inversion model is a combination of the radiative transfer theory with dense medium phase and amplitude correction theory (DMPACT), and the Levenberg-Marquardt optimization algorithm. The radiative transfer theory was applied as the forward model to generate radar backscatter data, while the DMPACT was included to account for the close spacing effect among the scatterers within the medium. The Levenberg-Marquardt optimization algorithm was then applied to reduce the error between the model generated radar backscatter data and the measured radar backscatter data from satellite images so that the sea ice thickness could be estimated. The second method presented was the neural network inversion method which utilizes a chain of neurons with variable weights. Once the network was fully operational it would be possible to predict the sea ice thickness, provided sufficient training data are given. The last method was the genetic algorithm which is a search technique used in order to predict the approximate sea ice thickness from the measured data. Data from ground truth measurements carried out in Ross Island, Antarctica, together with radar backscatter data extracted from purchased satellite images were used as input to verify the models. All three models were tested and successfully predicted sea ice thickness from actual terrain using the ground truth measurement data, with several constraints and assumptions placed to avoid problems during the retrieval process. While the models still have their own limitations, the potential use of the models for actual sea ice thickness retrieval was confirmed.

Matched MeSH terms: Neurons
Extending the range of an optical vanadium(v) sensor based on immobilized fatty hydroxamic acid in poly (methyl methacrylate) using artificial neural network

Azizul Isha, Nor Azah Yusof, Musa Ahmad, Dedy Suhendra, Wan Md. Zin Wan Yunus, Zulkarnain Zainal

Pertanika Journal of Science & Technology, 2007;15(2):121-130.
MyJurnal

An artificial neural network (ANN) was applied for the determination of V(V) based on immobilized fatty hydroxamic acid (FHA) in poly(methyl methacrylate) (PMMA). Spectra obtained from the V(V)-FHA complex at single wavelengths was used as the input data for the ANN. The V(V)-FHA complex shows a limited linear dynamic range of V(V) concentration of 10 - 100 mg/ L. After training with ANN, the linear dynamic range was extended with low calibration error. A three layer feed forward neural network using backpropagation (BP) algorithm was employed in this study. The input layer consisted of single neurons, 30 neurons in hidden a layer and one output neuron was found appropriate for the multivariate calibration used. The network were trained up to 10000 epochs with 0.003 % learning rate. This reagent also provided a good analytical pedormance with reproducibility characters of the method yielding relative standard deviation (RSD) of 9.29% and 7.09% for V(V) at concentrations of 50 mg/ L and 200 mg/ L, respectively. The limit of detection of the method was 8.4 mg/ L.

Matched MeSH terms: Neurons
The USM human genome centre experience on molecular diagnostic testing of spinal muscular atrophy

Fatemeh, H., Watihayati, M.S., Marini, M., NurShafawati, A.R., Atif, A.B., Zabidi-Hussin, Z.A.M.H., et al.

Malaysian Journal of Paediatrics and Child Health, 2007;15(1):24-0.
MyJurnal

Spinal Muscular Atrophy (SMA) is a heredity neuromuscular disorder and is one of the most common genetic causes of childhood fatality. SMA is classified into three groups based on age of onset and achieved motor milestone. Survival Motor Neuron (SMN) gene has been identified as the responsible gene for SMA. From August 2003 until Feb 2007 we have received 93 samples for SMN1 gene deletion analysis from various hospitals in Malaysia. All the patients except for 3 patients were Malaysian (71 Malays, 5 Indians, 9 Chinese and 5 patients are mixed ethnicity). DNA were extracted from blood samples using DNA extraction kit and subjected to SMN/ gene deletion analysis by PCR-RE. Forty nine out of 93 samples (20 type I, 21 type II, and 8 type III) were found to have homozygous deletion of at least exon 7 of the SMN1 gene. Twelve patients (7 type I, 4 type II, 1 type III) showed the presence of the SMN1 gene and the rest were excluded as they did not fulfill the criteria of International SMA Consortium. Deletion analysis of exon 7 of the SMN gene can be an alternative to the existing diagnostic modalities of SMA.

Matched MeSH terms: Motor Neurons
Fulltext Cellular and molecular profiles of anterior nervous system regeneration in Diopatra claparedii Grube, 1878 (Annelida, Polychaeta)

Ahmad Nazri MUI, Mahmud MH, Saidi B, Mat Isa MN, Ehsak Z, Ross O, et al.

Heliyon, 2021 Feb;7(2):e06307.
PMID: 33681499 DOI: 10.1016/j.heliyon.2021.e06307

The polychaete Diopatra claparedii Grube, 1878 is among those organisms successfully carrying out full body regeneration, including the whole nervous system. Thus, D. claparedii potentially can be regarded for the nervous system regeneration (NSR) study. However, data on the property of its nervous system and the NSR profile are still lacking. In this study, we investigated the morphology of D. claparedii anterior nervous system (ANS) and examined the cellular and molecular profiles on its early anterior NSR. The nervous system of D. claparedii consists of a symmetry brain with nerves branching off, circumpharyngeal connectives that connect the brain and nerve cord as well as obvious segmental ganglia. Moreover, we identified changes in the cellular condition of the ganglionic cells in the regenerating tissue, such as the accumulation of lysosomes and lipofuscins, elongated mitochondria and multiple nucleoli. Furthermore, mRNA of tissues at two regenerating stages, as well as intact tissue (non-regenerating), were sequenced with Illumina sequencer. We identified from these tissues 37,248 sequences, 18 differential expressed proteins of which upregulated were involved in NSR with noelin-like isoform X2 turned up to be the highest being expressed. Our results highlight the cellular and molecular changes during early phase of NSR, thus providing essential insights on regeneration within Annelida and understanding the neurodegenerative diseases.

Matched MeSH terms: Neurons
Fulltext MDMA and the Brain: A Short Review on the Role of Neurotransmitters in Neurotoxicity

Mustafa NS, Bakar NHA, Mohamad N, Adnan LHM, Fauzi NFAM, Thoarlim A, et al.

Basic Clin Neurosci, 2020 07 01;11(4):381-388.
PMID: 33613876 DOI: 10.32598/bcn.9.10.485

N-Methyl-3, 4-methylenedioxyamphetamine (MDMA), or ecstasy is a recreational drug of abuse. It is a synthetic substance that affects the body's systems, which its mechanism of action and treatment should be more investigated. MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure. Only a few studies have been done regarding its treatment. Thus, the treatment of MDMA complications should be further explored mainly by targeting its mechanism of action in the neurotransmitter systems. Hence, this study presents a short review regarding the recent findings on the role of neurotransmitters to cause MDMA neurotoxicity. The results will be useful for future research in elucidating the potential treatment based on the targeted mechanisms to treat the neurotoxic effects of MDMA.

Matched MeSH terms: Neurons
Fulltext Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology

Banka S, Bennington A, Baker MJ, Rijckmans E, Clemente GD, Ansor NM, et al.

Brain, 2022 Dec 19;145(12):4232-4245.
PMID: 35139179 DOI: 10.1093/brain/awac049

RAC1 is a highly conserved Rho GTPase critical for many cellular and developmental processes. De novo missense RAC1 variants cause a highly variable neurodevelopmental disorder. Some of these variants have previously been shown to have a dominant negative effect. Most previously reported patients with this disorder have either severe microcephaly or severe macrocephaly. Here, we describe eight patients with pathogenic missense RAC1 variants affecting residues between Q61 and R68 within the switch II region of RAC1. These patients display variable combinations of developmental delay, intellectual disability, brain anomalies such as polymicrogyria and cardiovascular defects with normocephaly or relatively milder micro- or macrocephaly. Pulldown assays, NIH3T3 fibroblast spreading assays and staining for activated PAK1/2/3 and WAVE2 suggest that these variants increase RAC1 activity and over-activate downstream signalling targets. Axons of neurons isolated from Drosophila embryos expressing the most common of the activating variants are significantly shorter, with an increased density of filopodial protrusions. In vivo, these embryos exhibit frequent defects in axonal organization. Class IV dendritic arborization neurons expressing this variant exhibit a significant reduction in the total area of the dendritic arbour, increased branching and failure of self-avoidance. RNAi knock down of the WAVE regulatory complex component Cyfip significantly rescues these morphological defects. These results establish that activating substitutions affecting residues Q61-R68 within the switch II region of RAC1 cause a developmental syndrome. Our findings reveal that these variants cause altered downstream signalling, resulting in abnormal neuronal morphology and reveal the WAVE regulatory complex/Arp2/3 pathway as a possible therapeutic target for activating RAC1 variants. These insights also have the potential to inform the mechanism and therapy for other disorders caused by variants in genes encoding other Rho GTPases, their regulators and downstream effectors.

Matched MeSH terms: Neurons

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