Molecular Neurobiology Research Articles

Molecular and Cellular Neurobiology of Spreading Depolarization/Depression and Migraine: A Narrative Review.

Migraine is a prevalent neurological disorder, particularly among individuals aged 20-50 years, with significant social and economic impacts. Despite its high prevalence, the pathogenesis of migraine remains unclear. In this review, we provide a comprehensive overview of cortical spreading depolarization/depression (CSD) and its close association with migraine aura, focusing on its role in understanding migraine pathogenesis and therapeutic interventions. We discuss historical studies that have demonstrated the role of CSD in the visual phenomenon of migraine aura, along with modern imaging techniques confirming its propagation across the occipital cortex. Animal studies are examined to indicate that CSD is not exclusive to migraines; it also occurs in other neurological conditions. At the cellular level, we review how CSD is characterized by ionic changes and excitotoxicity, leading to neuronal and glial responses. We explore how CSD activates the trigeminal nervous system and upregulates the expression of calcitonin gene-related peptides (CGRP), thereby contributing to migraine pain. Factors such as genetics, obesity, and environmental conditions that influence the CSD threshold are discussed, suggesting potential therapeutic targets. Current treatments for migraine, including prophylactic agents and CGRP-targeting drugs, are evaluated in the context of their expected effects on suppressing CSD activity. Additionally, we highlight emerging therapies such as intranasal insulin-like growth factor 1 and vagus nerve stimulation, which have shown promise in reducing CSD susceptibility and frequency. By elucidating the molecular and cellular mechanisms of CSD, this review aims to enhance the understanding of migraine pathogenesis and support the development of targeted therapeutic strategies.

Illana Gozes: From the pivotal discovery of activity-dependent neuroprotective protein (ADNP) through its investigational drug davunetide: brain molecular medicine providing hope for autism, schizophrenia, and Alzheimer's disease

Professor Illana Gozes, Ph.D., is a faculty member at Tel Aviv University. Formerly holding the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, she now directs the Dr. Diana and Zelma Elton Laboratory for Molecular Neuroendocrinology. A world-renowned neurochemist, Professor Gozes currently serves as the President of the European Society for Neurochemistry and Vice President of Drug Development at ExoNavis Therapeutics Ltd. Her groundbreaking research began in the late 1970s and early 1980s when she discovered multiple tubulin forms within a single neuron. She demonstrated that these forms evolve with brain development, play a crucial role in synapse formation, and can be identified using monoclonal tubulin antibodies. At the forefront of molecular neuroscience in the 1980s, Professor Gozes became the first to clone the gene encoding vasoactive intestinal peptide (VIP), a key regulatory neuropeptide in the brain. Her research revealed increased VIP expression during synapse formation. In her quest to identify proteins activated by VIP and facilitate neuro-glial interaction, the Gozes laboratory discovered and cloned a novel protein: activity-dependent neuroprotective protein (ADNP). Subsequent research established ADNP's essential role in brain formation and function. Through a series of highly cited articles, Professor Gozes demonstrated that ADNP regulates thousands of essential genes during brain development in a sex-dependent manner and associates with an intricate array of vital proteins. She uncovered ADNP's key role in autophagy and schizophrenia, revealed a fundamental shared mechanism in autism involving critical binding of ADNP with SHANK3 and actin, and showed ADNP's regulation of microtubule dynamics and Tau interaction, which protects against tauopathy. Furthermore, she discovered somatic mutations in ADNP and related genes in Alzheimer's disease, paralleling tauopathy. Her pioneering work on ADNP-deficient mouse models predicted the ADNP syndrome, an autistic/intellectual disability syndrome driven by de novo mutations in ADNP and presenting with tauopathy. Professor Gozes took a reductionist approach to discover an active site in ADNP, leading to the development of the investigational drug davunetide (NAP). This compound has shown promise in protecting against ADNP deficiency/mutations in animal models and in clinical trials. It has been tested in women suffering from progressive supranuclear palsy (PSP), a pure tauopathy, and in individuals with prodromal Alzheimer's disease, demonstrating effects in a sex-dependent manner. Further promise was shown in schizophrenia patients, suggesting improvement in real-world problem solving and task performance. We are honored that Professor Gozes has agreed to share her life's journey with our readers in this Genomic Press Interview.

Hermona Soreq: Revolutionizing neuroscience by elucidating the roles of poly(A) tails, mRNA stability, and acetylcholine in brain-body communication throughout the lifespan

Hermona Soreq, PhD, holds the Endowed Slesinger Professorship of Molecular Neuroscience at the Hebrew University of Jerusalem. She is an internationally recognized molecular neuroscientist known for her research into the cholinergic system and the small RNA regulators driving the parasympathetic system in men and women under daily and acute stress responses and neurodegenerative diseases like Alzheimer's and Parkinson's diseases (AD, PD). Her studies have long been focused on the roles of acetylcholine in the mammalian nervous system. In the 1980s, Professor Soreq and coworkers cloned the human cholinesterase genes, identified several disease-related mutations and single nucleotide polymorphisms (SNPs) that may impair their functions, and described the unusual features these mutations conferred on carriers under acute stress, exposure to anticholinesterase poisons and diverse disease conditions, including but not limited to myasthenia gravis, ischemic stroke, schizophrenia, bipolar disorder, AD and PD as well as daily stress responses. Soreq further identified microRNA-132 as a principal controller of the cholinergic pathway and studied its impact as well as of other cholinergic-targeted microRNAs as regulators of parasympathetic brain and body functions and neuroinflammation. More recently, she has shifted her interest to the re-discovered transfer RNA fragments (tRFs), and showed that their rapidly declined control over cholinergic transcripts may lead to the fast cognitive deterioration of women living with AD; that they are prominently altered in PD patients’ biofluids and that their levels are sex-relatedly modified in the blood of newborn babies, dependent on pre-delivery stress. Her multi-leveled interests in the stress and sex-related cholinergic aspects of AD, PD, adult, and pre-delivery trauma further reflect the impact on acute stress responses as the kernel of the neuroscience research in the current Israeli landscape and has further enabled her a wide-angle view of diverse cholinergic-regulated states and diseases. We are delighted that Professor Soreq answered the Genomic Press Interview, generously sharing her life's trajectory with our readers.

Bioelectronic Medicines-A Novel Approach of Therapeutics in Current Epoch.

Bioelectronic medicines aim to diagnose and treat a wide range of illnesses and ailments, including cancer, rheumatoid arthritis, inflammatory bowel disease, obesity, diabetes, asthma, paralysis, blindness, bleeding, ischemia, organ transplantation, cardiovascular disease, and neurodegenerative diseases. The focus of bioelectronic medicine is on electrical signaling of the nervous system. Understanding the nervous system's regulatory roles and developing technologies that record, activate, or inhibit neural signaling to influence particular biological pathways. Bioelectronic medicine is an emerging therapeutic option with the interconnection between molecular medicine, neuroscience, and bioengineering. The creation of nerve stimulating devices that communicate with both the central and peripheral nervous systems has the potential to completely transform how we treat disorders. Although early clinical applications have been largely effective across entire nerves, the ultimate goal is to create implantable, miniature closed-loop systems that can precisely identify and modulate individual nerve fibers to treat a wide range of disorders. The data bases such as PubMed, and Clinicaltrial.gov.in were searched for scientific research, review and clinical trials on bioelectronic medicine. The field of bioelectronic medicine is trending at present. In recent years, researchers have extended the field's applications, undertaken promising clinical trials, and begun delivering therapies to patients, thus creating the groundwork for significant future advancements. Countries and organizations must collaborate across industries and regions to establish an atmosphere and guidelines that foster the advancement of the field and the fulfillment of its prospective advantages.

Assessing Stroke Recurrence Risk by Using a Lipoprotein-Associated Phospholipase A2 and Platelet Count-Based Nomogram.

Stroke recurrence remains a critical challenge in clinical neurology, necessitating the identification of reliable predictive markers for better management and treatment strategies. This study investigates the interaction between lipoprotein-associated phospholipase A2 (Lp-PLA2) and platelets as a potential predictor for stroke recurrence, aiming to refine risk assessment and therapeutic approaches. In a retrospective cohort of 580 ischemic stroke patients, we analyzed clinical data with a focus on Lp-PLA2 and platelet levels. By using multivariable logistic regression, we identified independent predictors of stroke recurrence. These predictors were then used to develop a comprehensive nomogram. The study established diabetes mellitus, hypertension, low-density lipoprotein (LDL), Lp-PLA2 levels, and platelet counts as independent predictors of stroke recurrence. Crucially, the interaction parameter Lp-PLA2 * platelet (multiplication of Lp-PLA2 and platelet count) exhibited superior predictive power over each factor considered separately. Our nomogram incorporated diabetes mellitus, cerebral infarction causes, hypertension, LDL, and the Lp-PLA2 * platelet count interaction and demonstrated enhanced accuracy in predicting stroke recurrence compared to traditional risk models. The interaction between Lp-PLA2 and platelets emerged as a significant predictor for stroke recurrence when integrated with traditional risk factors. The developed nomogram offers a novel and practical tool in molecular neurobiology for assessing individual risks, facilitating personalized treatment strategies. This approach underscores the importance of multifactorial assessment in stroke management and opens avenues for targeted interventions to mitigate recurrence risks.

Optogenetic Brain-Computer Interfaces.

The brain-computer interface (BCI) is one of the most powerful tools in neuroscience and generally includes a recording system, a processor system, and a stimulation system. Optogenetics has the advantages of bidirectional regulation, high spatiotemporal resolution, and cell-specific regulation, which expands the application scenarios of BCIs. In recent years, optogenetic BCIs have become widely used in the lab with the development of materials and software. The systems were designed to be more integrated, lightweight, biocompatible, and power efficient, as were the wireless transmission and chip-level embedded BCIs. The software is also constantly improving, with better real-time performance and accuracy and lower power consumption. On the other hand, as a cutting-edge technology spanning multidisciplinary fields including molecular biology, neuroscience, material engineering, and information processing, optogenetic BCIs have great application potential in neural decoding, enhancing brain function, and treating neural diseases. Here, we review the development and application of optogenetic BCIs. In the future, combined with other functional imaging techniques such as near-infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI), optogenetic BCIs can modulate the function of specific circuits, facilitate neurological rehabilitation, assist perception, establish a brain-to-brain interface, and be applied in wider application scenarios.

Translational Relevance of Secondary Intracellular Signaling Cascades Following Traumatic Spinal Cord Injury.

Traumatic spinal cord injury (SCI) is a life-threatening and life-altering condition that results in debilitating sensorimotor and autonomic impairments. Despite significant advances in the clinical management of traumatic SCI, many patients continue to suffer due to a lack of effective therapies. The initial mechanical injury to the spinal cord results in a series of secondary molecular processes and intracellular signaling cascades in immune, vascular, glial, and neuronal cell populations, which further damage the injured spinal cord. These intracellular cascades present promising translationally relevant targets for therapeutic intervention due to their high ubiquity and conservation across eukaryotic evolution. To date, many therapeutics have shown either direct or indirect involvement of these pathways in improving recovery after SCI. However, the complex, multifaceted, and heterogeneous nature of traumatic SCI requires better elucidation of the underlying secondary intracellular signaling cascades to minimize off-target effects and maximize effectiveness. Recent advances in transcriptional and molecular neuroscience provide a closer characterization of these pathways in the injured spinal cord. This narrative review article aims to survey the MAPK, PI3K-AKT-mTOR, Rho-ROCK, NF-κB, and JAK-STAT signaling cascades, in addition to providing a comprehensive overview of the involvement and therapeutic potential of these secondary intracellular pathways following traumatic SCI.

Unraveling the Complexity of Seizures and Epilepsies: a Multifaceted Approach to Classification, Syndromes, Causes, and Integrated Therapies

Objective: To investigate the clinical diversity, genetic bases, diagnostic complexity, and therapeutic approaches of epileptic syndromes, highlighting recent advances in understanding these disorders. Theoretical Framework: Epileptic syndromes are neurological disorders characterized by recurrent epileptic seizures, resulting from abnormal neuronal activity in the brain, whose classification has evolved towards clinical and genetic criteria. Method: A systematic approach was employed for bibliographic review on epileptic syndromes, consulting biomedical databases and applying strict selection criteria. Studies addressing clinical diversity, genetic bases, and diagnostic complexity were included, followed by qualitative data analysis to identify patterns and gaps in the literature. Results and Discussion: Results reveal evident genetic heterogeneity, with some syndromes exhibiting well-defined genetic bases. Advances in genomics and molecular neurobiology have provided insights into pathogenic mechanisms, despite persistent challenges, including resistance to conventional medications. Implications of the Research: In-depth understanding is crucial for accurate diagnosis and effective therapeutic development, emphasizing the continuous need for research to improve clinical outcomes and quality of life for patients. Originality/Value: Highlights recent advances in understanding epileptic syndromes, identifying key areas for future research, and contributing to better comprehension and quality of life for affected patients.

Exploring the Gut-Brain Axis: A Comprehensive Review of Interactions Between the Gut Microbiota and the Central Nervous System

The gut-brain axis represents a complex network of interactions among the gut microbiota, the enteric nervous system (ENS), the autonomic nervous system (ANS), and the central nervous system (CNS), exerting profound influences on both digestive and mental health. Dysfunction within this axis has been implicated in a spectrum of disorders ranging from irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) to depression, anxiety, and neurodegenerative conditions. While early observations of the relationship between emotions and gastrointestinal function date back to the early 20th century, recent decades have witnessed significant strides in understanding this intricate interplay, fueled by advancements in molecular biology, microbiology, and neuroscience. Key milestones include the discovery of the enteric nervous system, elucidation of gut hormone functions, and recognition of the pivotal role played by gut microbiota in shaping brain function and behavior. The gut microbiota, comprising trillions of microorganisms residing within the gastrointestinal tract, actively contribute to gut-brain communication by producing an array of metabolites, neurotransmitters, and immune modulators. This communication pathway underscores the critical importance of comprehending the intricate interplay between gut microbiota and the central nervous system for devising innovative therapeutic interventions targeting a broad spectrum of psychiatric and neurological disorders. Furthermore, lifestyle factors such as diet, stress, and antibiotic usage wield significant influence over the composition and functionality of gut microbiota, thereby emphasizing the pivotal role of lifestyle interventions in fostering and preserving gut-brain health. This abstract encapsulates the current understanding of the gut-brain axis, highlighting its multifaceted implications for health and disease management, and underscores the pressing need for continued research to unlock its therapeutic potential.

What do the mushroom bodies do for the insect brain? Twenty-five years of progress.

In 1998, a special edition of Learning & Memory was published with a discrete focus of synthesizing the state of the field to provide an overview of the function of the insect mushroom body. While molecular neuroscience and optical imaging of larger brain areas were advancing, understanding the basic functioning of neuronal circuits, particularly in the context of the mushroom body, was rudimentary. In the past 25 years, technological innovations have allowed researchers to map and understand the in vivo function of the neuronal circuits of the mushroom body system, making it an ideal model for investigating the circuit basis of sensory encoding, memory formation, and behavioral decisions. Collaborative efforts within the community have played a crucial role, leading to an interactive connectome of the mushroom body and accessible genetic tools for studying mushroom body circuit function. Looking ahead, continued technological innovation and collaborative efforts are likely to further advance our understanding of the mushroom body and its role in behavior and cognition, providing insights that generalize to other brain structures and species.

A COMPREHENSIVE REVIEW ON UNRAVELLING THE INTRICACIES OF MOLECULAR NEUROSCIENCE

Molecular neuroscience is a multidisciplinary field dedicated to unravelling the molecular mechanisms underlying brain function and dysfunction. This comprehensive review provides an overview of recent advancements in molecular neuroscience, spanning from neuronal signalling pathways to the genetic basis of neurological disorders covered encompass synaptic plasticity and learning, neurodevelopment and synaptogenesis, neurotransmitter systems, and the genetic underpinnings of neurological disorders. Advances in techniques such as optogenetics, calcium imaging, and genomic technologies have revolutionized our understanding of the brain at the molecular level. Moreover, emerging technologies such as single-cell RNA sequencing and CRISPR/Cas9 genome editing hold promise for further elucidating the complexities of the nervous system. By integrating molecular, cellular, and systems-level approaches, molecular neuroscience continues to pave the way for novel insights into brain function and the development of targeted therapeutics for neurological diseases.

Unraveling the mysteries of the brain: Advances and challenges in clinical neurology

This work offers a comprehensive analysis of advances and challenges in contemporary clinical neurology, with a focus on understanding the human brain and its diseases. We review the latest advances in neuroimaging techniques, molecular neuroscience, and neuroprotective therapies, highlighting their importance for understanding and treating a variety of neurological conditions. However, we also discuss persistent challenges, including the clinical heterogeneity of neurological diseases, ethical issues related to the use of neuroscientific technologies, and the need for personalized therapeutic approaches. We conclude that a multidisciplinary and collaborative approach is essential to address these complex challenges and promote significant advances in clinical neurology.

The physiological role of TRP channels in sleep and circadian rhythm.

TRP channels, are non-specific cationic channels that are involved in multiple physiological processes that include salivation, cellular secretions, memory extinction and consolidation, temperature, pain, store-operated calcium entry, thermosensation and functionality of the nervous system. Here we choose to look at the evidence that decisively shows how TRP channels modulate human neuron plasticity as it relates to the molecular neurobiology of sleep/circadian rhythm. There are numerous model organisms of sleep and circadian rhythm that are the results of the absence or genetic manipulation of the non-specific cationic TRP channels. Drosophila and mice that have had their TRP channels genetically ablated or manipulated show strong evidence of changes in sleep duration, sleep activity, circadian rhythm and response to temperature, noxious odours and pattern of activity during both sleep and wakefulness along with cardiovascular and respiratory function during sleep. Indeed the role of TRP channels in regulating sleep and circadian rhythm is very interesting considering the parallel roles of TRP channels in thermoregulation and thermal response with concomitant responses in growth and degradation of neurites, peripheral nerves and neuronal brain networks. TRP channels provide evidence of an ability to create, regulate and modify our sleep and circadian rhythm in a wide array of physiological and pathophysiological conditions. In the current review, we summarize previous results and novel recent advances in the understanding of calcium ion entry via TRP channels in different sleep and circadian rhythm conditions. We discuss the role of TRP channels in sleep and circadian disorders.

Effect of Gene Knockout of CEP290 using CRISPR-Cas 9 Technology on Xenopus tropicalis

Modelling human diseases using the Xenopus species is an increasingly popular method to study vertebrate embryology and development, basic cell and molecular biology, genomics, neurobiology, and toxicology. This allows for the elucidation of the regulation mechanisms and interactive networks that affect the direct development of embryos, the adaptation process, and disease and malformation-causing dysregulations. Here we aim to analyze the possible kidney defects during the gene-knockout of CEP290 in X. tropicalis species. Our objectives are to produce sgRNA via de-novo synthesis from the constructed DNA template, to microinject synthesized sgRNA into embryos of Xenopus tropicalis, and to determin the success of the genome editing via T7-Endonuclease I assay and observation of genetically modified tadpoles for identifying any physical symptoms produced due to gene knockout. The data obtained from the embryos of X. tropicalis suggests that complete knock-out of the gene cep290 results in severe mutation that causes death.

Uncovering the determinants of brain functioning, behavior and their interplay in the light of context.

Notwithstanding the huge progress in molecular and cellular neuroscience, our ability to understand the brain and develop effective treatments promoting mental health is still limited. This can be partially ascribed to the reductionist, deterministic and mechanistic approaches in neuroscience that struggle with the complexity of the central nervous system. Here, I introduce the Context theory of constrained systems proposing a novel role of contextual factors and genetic, molecular and neural substrates in determining brain functioning and behavior. This theory entails key conceptual implications. First, context is the main driver of behavior and mental states. Second, substrates, from genes to brain areas, have no direct causal link to complex behavioral responses as they can be combined in multiple ways to produce the same response and different responses can impinge on the same substrates. Third, context and biological substrates play distinct roles in determining behavior: context drives behavior, substrates constrain the behavioral repertoire that can be implemented. Fourth, since behavior is the interface between the central nervous system and the environment, it is a privileged level of control and orchestration of brain functioning. Such implications are illustrated through the Kitchen metaphor of the brain. This theoretical framework calls for the revision of key concepts in neuroscience and psychiatry, including causality, specificity and individuality. Moreover, at the clinical level, it proposes treatments inducing behavioral changes through contextual interventions as having the highest impact to reorganize the complexity of the human mind and to achieve a long-lasting improvement in mental health.

The origin of 2,5-dimethoxy-4-methylamphetamine (DOM, STP).

The story of the 1967 appearance of the powerful psychedelic 2,5-dimethoxy-4-methylamphetamine (DOM, STP) commonly omits details and often includes hyperbole and inaccuracies. It is well known how and when the drug was first distributed to the public for free by Owsley Stanley, but the role that Alexander Shulgin played in providing that material is not as well understood. In the interest of transparency and historical accuracy, this article attempts to present an accurate account of this well-known but inadequately detailed event. It follows DOM's development as an experimental substance believed to hold potential promise in psychotherapeutic applications through its appearance as a street drug generating bad press and a lasting bad impression among the public. One of the more interesting questions is why Shulgin would have taken such an immense risk in releasing this material to clandestine operators. While DOM was still legal it was also Dow's intellectual property, so discovery of his involvement could have jeopardized his career. The escape is especially curious as all fingers would logically first point towards Shulgin as the source. Drawing from published and unpublished sources, the authors attempt to suggest answers. DOM rapidly faded into oblivion before human pharmacodynamics and pharmacokinetics could be established. In this account, the reader is informed of the potential value that the compound played in non-clinical molecular neuroscience, elucidating receptor specificity of new drugs, and how mistaken warnings about combining DOM with chlorpromazine led to better non-pharmacological drug crisis response.

MicroRNA-29b-3p degenerates terminally differentiated dopaminergic SH-SY5Y cells by perturbation of mitochondrial functions.

Mitochondrial dysfunction is the main cause of gradual deterioration of structure and function of neuronal cells, eventually resulting in neurodegeneration. Studies have revealed a complex interrelationship between neurotoxicant exposure, mitochondrial dysfunction, and neurodegenerative diseases. Alteration in the expression of microRNAs (miRNAs) has also been linked with disruption in mitochondrial homeostasis and bioenergetics. In our recent research (Cellular and Molecular Neurobiology (2023) https://doi.org/10.1007/s10571-023-01362-4), we have identified miR-29b-3p as one of the most significantly up-regulated miRNAs in the blood of Parkinson's patients. The findings of the present study revealed that neurotoxicants of two different natures, that is, arsenic or rotenone, dramatically increased miR-29b-3p expression (18.63-fold and 12.85-fold, respectively) in differentiated dopaminergic SH-SY5Y cells. This dysregulation of miR-29b-3p intricately modulated mitochondrial morphology, induced oxidative stress, and perturbed mitochondrial membrane potential, collectively contributing to the degeneration of dopaminergic cells. Additionally, using assays for mitochondrial bioenergetics in live and differentiated SH-SY5Y cells, a reduction in oxygen consumption rate (OCR), maximal respiration, basal respiration, and non-mitochondrial respiration was observed in cells transfected with mimics of miR-29b-3p. Inhibition of miR-29b-3p by transfecting inhibitor of miR-29b-3p prior to exposure to neurotoxicants significantly restored OCR and other respiration parameters. Furthermore, we observed that induction of miR-29b-3p activates neuronal apoptosis via sirtuin-1(SIRT-1)/YinYang-1(YY-1)/peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1α)-regulated Bcl-2 interacting protein 3-like-dependent mechanism. Collectively, our studies have shown the role of miR-29b-3p in dysregulation of mitochondrial bioenergetics during degeneration of dopaminergic neurons via regulating SIRT-1/YY-1/PGC-1α axis.

A Bright Future? A Perspective on Class C GPCR Based Genetically Encoded Biosensors.

One of the major challenges in molecular neuroscience today is to accurately monitor neurotransmitters, neuromodulators, peptides, and various other biomolecules in the brain with high temporal and spatial resolution. Only a comprehensive understanding of neuromodulator dynamics, their release probability, and spatial distribution will unravel their ultimate role in cognition and behavior. This Perspective offers an overview of potential design strategies for class C GPCR-based biosensors. It briefly highlights current applications of GPCR-based biosensors, with a primary focus on class C GPCRs and their unique structural characteristics compared with other GPCR subfamilies. The discussion offers insights into plausible future design approaches for biosensor development targeting members of this specific GPCR subfamily. It is important to note that, at this stage, we are contemplating possibilities rather than presenting a concrete guide, as the pipeline is still under development.

Neurochemical differences in core regions of the autistic brain: a multivoxel 1H-MRS study in children

Autism spectrum disorder (ASD) is a neurodevelopmental condition which compromises various cognitive and behavioural domains. The understanding of the pathophysiology and molecular neurobiology of ASD is still an open critical research question. Here, we aimed to address ASD neurochemistry in the same time point at key regions that have been associated with its pathophysiology: the insula, hippocampus, putamen and thalamus. We conducted a multivoxel proton magnetic resonance spectroscopy (1H-MRS) study to non-invasively estimate the concentrations of total choline (GPC + PCh, tCho), total N-acetyl-aspartate (NAA + NAAG, tNAA) and Glx (Glu + Gln), presenting the results as ratios to total creatine while investigating replication for ratios to total choline as a secondary analysis. Twenty-two male children aged between 10 and 18 years diagnosed with ASD (none with intellectual disability, in spite of the expected lower IQ) and 22 age- and gender-matched typically developing (TD) controls were included. Aspartate ratios were significantly lower in the insula (tNAA/tCr: p = 0.010; tNAA/tCho: p = 0.012) and putamen (tNAA/tCr: p = 0.015) of ASD individuals in comparison with TD controls. The Glx ratios were significantly higher in the hippocampus of the ASD group (Glx/tCr: p = 0.027; Glx/tCho: p = 0.011). Differences in tNAA and Glx indices suggest that these metabolites might be neurochemical markers of region-specific atypical metabolism in ASD children, with a potential contribution for future advances in clinical monitoring and treatment.

A bibliometric and visual analysis of epigenetic research publications for Alzheimer's disease (2013-2023).

Currently, the prevalence of Alzheimer's disease (AD) is progressively rising, particularly in developed nations. There is an escalating focus on the onset and progression of AD. A mounting body of research indicates that epigenetics significantly contributes to AD and holds substantial promise as a novel therapeutic target for its treatment. The objective of this article is to present the AD areas of research interest, comprehend the contextual framework of the subject research, and investigate the prospective direction for future research development. ln Web of Science Core Collection (WOSCC), we searched documents by specific subject terms and their corresponding free words. VOSviewer, CiteSpace and Scimago Graphica were used to perform statistical analysis on measurement metrics such as the number of published papers, national cooperative networks, publishing countries, institutions, authors, co-cited journals, keywords, and visualize networks of related content elements. We selected 1,530 articles from WOSCC from January 2013 to June 2023 about epigenetics of AD. Based on visual analysis, we could get that China and United States were the countries with the most research in this field. Bennett DA was the most contributed and prestigious scientist. The top 3 cited journals were Journal of Alzheimer's Disease, Neurobiology of Aging and Molecular Neurobiology. According to the analysis of keywords and the frequency of citations, ncRNAs, transcription factor, genome, histone modification, blood DNA methylation, acetylation, biomarkers were hot research directions in AD today. According to bibliometric analysis, epigenetic research in AD was a promising research direction, and epigenetics had the potential to be used as AD biomarkers and therapeutic targets.