Myelin Research Articles

Impact of air pollution on the clinical exacerbation of central demyelinating disease: A 10-year data from the Northern Thailand MS and NMOSD registry.

Particulate matter (PM) 2.5 (PM2.5) and PM10 are implicated in neurological diseases, yet their impact on central demyelinating diseases like multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) remains unclear. This study aimed to determine the association between the levels of PM2.5 and PM10 and the exacerbation of MS and NMOSD. Patients with clinical exacerbations of MS and NMOSD in the Northern Thailand Registry from 2013 to 2022 were enrolled. Eligible patients were categorized based on air pollution exposure (defined as PM2.5 > 15 μg/m3 and PM10 > 45 μg/m3) or no air pollution exposure. Outcomes assessed included clinical characteristics, Expanded Disability Status Scale (EDSS), and functional outcomes. We analyzed 126 exacerbations in the PM2.5 database (mean age: 44.9±14.9 years, 114 NMOSD, 49 first exacerbations) and 135 exacerbations with the PM10 database (mean age: 44.9±14.9 years, 121 NMOSD, 54 first exacerbations), with the highest incidence four months post-peak air pollution. The PM2.5 exposure group had higher severity, showing increased rates of unfavorable EDSS at exacerbation and 90 days (56.3% vs. 23.6%, P < 0.001 and 47.9% vs. 16.4%, P < 0.001, respectively). Gadolinium enhancement in PM2.5 exposure was significantly higher (56.3% vs. 36.4%, P = 0.03). The PM2.5 exposure group also had a higher rate of second-line therapy with plasma exchange (21.1% vs. 7.3%, P = 0.03). PM2.5 exposure, not PM10, was associated with unfavorable EDSS at any time point, active radiological activity, risk of plasma exchange, and prolonged hospitalization. Environmental pollution, especially PM2.5, significantly impacts MS and NMOSD patients, influencing disease severity, causing permanent disability, and prolonging hospitalization. A national policy on pollution control is imperative, and further data on long-term exposure, together with other pollutants, is still required.

Lysophosphatidylcholine induces ceramide synthase-2 expression in primary culture model of astrocytopathy: potential therapeutic target in multiple sclerosis.

Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination. Therefore, in the present study, the expression level of CS-2 has been evaluated in lysophosphatidylcholine (LPC)-challenged primary astrocytes in the presence of anti-demyelinating agents such as Fingolimod, a clinically approved anti-demyelinating drug, and Ursolic Acid (UA), an experimentally accepted anti-demyelinating agent, in MS. LPC (150µg/ml) caused astrocytopathy evident by decrease in percentage of viable astrocytes, increase in percentage of apoptotic astrocytes, increase in the level of reactive oxygen species (ROS), and increase in the level of activated astrocytes. Interestingly, LPC significantly increased the expression level of CS-2 in the primary culture of astrocytes where as fingolimod and UA (1, 10, and 100µM) were able to attenuate the extent of LPC-induced astrocytopathy in the primary culture model of MS. Further, both the drugs drastically reduced the LPC-induced increase in the level of expression of CS-2 in the astrocytes. These observations indicate the fact that CS-2 could be a potential target in the management of astrocytopathy and astrocytopathy-related neurological disorders including MS. In conclusion, CS-2-targeted drugs could be potential therapeutic options in the management of MS.

Spatial heterogeneity in myelin sheathing impacts signaling reliability and susceptibility to injury.

Axons in the mammalian brain show significant diversity in myelination motifs, displaying spatial heterogeneity in sheathing along individual axons and across brain regions. However, its impact on neural signaling and susceptibility to injury remains poorly understood. To address this, we leveraged cable theory and developed model axons replicating the myelin sheath distributions observed experimentally in different regions of the mouse central nervous system. We examined how the spatial arrangement of myelin affects propagation and predisposition to conduction failure in axons with cortical versus callosal myelination motifs. Our results indicate that regional differences inmyelination significantly influence conduction timing and signaling reliability. Sensitivity of action potential propagation to the specific positioning, lengths, and ordering of myelinated and exposed segments reveals non-linear and path-dependent conduction. Furthermore, myelination motifs impact signaling vulnerability to demyelination, with callosal motifs being particularly sensitive to myelin changes. These findings highlight the crucial role of myelinating glia in brain function and disease.Significance Statement This study highlights the importance of spatial heterogeneity of myelin sheathing in shaping nerve axonal conduction. Using model axons that faithfully replicate myelin distributions observed in the mouse central nervous system, our results revealed the impact of myelin patterns on the timing and reliability of neural signaling. Contrary to the conventional view in which uniform and equally spaced myelin segments imply linear conduction, our findings show that axonal conduction is a path-dependent, non-linear process influenced by the specific distribution of myelinated and unmyelinated segments. Membrane potential propagation along model axons in the corpus callosum was found to be more vulnerable to myelin changes compared to those in the cortex, especially post-myelin injury, emphasizing the role of sheath locations in both health and disease.

Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination.

The integrity of the myelin sheath of the spinal cord (SC) is essential for motor coordination. Seipin is an endoplasmic reticulum transmembrane protein highly expressed in adipose tissue and motor neurons in the SC. It was reported Seipin deficiency induced lipid dysregulation and neurobehavioral deficits, but the underlying mechanism, especially in SC, remains to be elucidated. In present study, we found that Seipin and myelin basic protein (MBP) increased synchronously in SC of developmental stage of mice. Demyelination impaired motor coordination as well as MBP and Seipin expression, which were alleviated by remyelination. Moreover, Seipin deficiency impaired motor coordination of mice, accompanied by hypomyelination in spinal cord. Mechanistically, we further demonstrated that myelin content as labeled by Fluormyelin, myelin basic protein (MBP) was down-regulated by Seipin deficiency. Seipin deficiency led to reduction of myelin-forming oligodendrocytes (OLs) density in spinal cord. Notably, administration of rosiglitazone (RG), a classic PPARγ activator, successfully restored the phenotypes manifested by Seipin deficiency including reduced OLs density, hypomyelination, as well as motor dyscoordination. In summary, present study revealed that Seipin deficiency disrupted motor coordination by compromising myelination in SC, and RG treatment could rescue the phenotypes. This study throws light on the mechanism underlying Seipin deficiency associated disorders and paves ways for developing therapeutics toward those diseases.

Advances in Multiple Sclerosis

Multiple sclerosis (MS) is the most common demyelinating and inflammatory disease of the CNS; it has a global distribution with increasing prevalence [...]

Neuroplasticity and Content of Structural Elements in the Axoplasm of the Trigeminal Nerve During the Eruption of Permanent Teeth in Humans

The aim of the presented study was to identify the features of the quantitative formation of axoplasmic organelles with a primary analysis of the components of the axonal cytoskeleton (microtubules and neurofilaments) of myelinated and non-myelinated nerve fibers in the dental pulp during the eruption of permanent teeth in humans. Material and methods. The neurovascular bundle of dental pulp was studied in children aged 5, 10 and 14 years. On ultramicrographs of pulp sections at a magnification of ×40000, the diameters of myelin and non-myelin conductors were measured; per 1 µm2 of axoplasm of nerve conductors, the density of axoplasmic organelles, the number of microtubules and neurofilaments were calculated. The reliability of differences between groups was assessed using multivariate analysis of variance (MANOVA), the significance of average values was assessed using the Tukey test, correlation analysis was carried out using the Pearson criterion. Results. The process of eruption of permanent teeth was accompanied by a gradual increase in the number of organelles per unit cross-sectional area of the nerve, regardless of its characteristics (myelinated or nonmyelinated fiber type). The highest density of organelles was observed in large-diameter fibers of both myelinated and non-myelinated conductors throughout the indicated segment of ontogenetic development. The presence of myelin in the nerve sheath correlates positively with microtubule saturation in fibers of large (r=0.267, p=0.001) and small (r=0.314, p=0.000) diameters, and negatively in fibers with medium diameter (r=-0.246, p=0.002). The proportion of neurofilaments represented among the axoplasmic organelles of the neuroplasm as a whole was especially high in myelinated and unmyelinated nerve fibers of small diameter, averaging up to 70%. The presence of the myelin sheath and fiber diameter are not associated with neurofilament density with the exception of medium-diameter fibers (r=0.195, p=0.001). Conclusion. The process of eruption of permanent teeth is accompanied by an increase in the number of organelles, cytoskeletal elements in the axoplasm of nerve fibers innervating the dental pulp, providing the morphological substrate of neuroplasticity, which must be taken into account, for example, in the process of dental implantation and dental prosthetics.

Plasmalogens Activate AKT/mTOR Signaling to Attenuate Reactive Oxygen Species Production in Spinal Cord Injury.

Plasmalogens, the primary phospholipids in the brain, possess intrinsic antioxidant properties and are crucial components of the myelin sheath surrounding neuronal axons. While their neuroprotective effects have been demonstrated in Alzheimer's disease, their potential benefits in spinal cord injury remain unexplored. This study investigates the reparative effects of plasmalogens on spinal cord injury and the underlying mechanisms. In vitro, we developed dorsal root ganglion (DRG) and RAW 264.7 cell models under high-reactive oxygen species (ROS) conditions to assess ROS levels, neuronal damage, and inflammatory microenvironment changes before and after plasmalogen application. In vivo, we used a complete mouse spinal cord transection model to evaluate changes in ROS levels, neuronal demyelination, and apoptosis following plasmalogen treatment. Additionally, we assessed sensory and motor function recovery and investigated the regulatory effects of plasmalogens on the AKT/mTOR signaling pathway. In high-ROS cell models, plasmalogens protected DRG neurons (TUJ-1) from axonal damage and modulated the proinflammatory/anti-inflammatory balance in RAW 264.7 cells. In vivo, plasmalogens significantly reduced ROS levels, improved the immune microenvironment, decreased the proinflammatory (iNOS)/anti-inflammatory (ARG-1) ratio, lowered neuronal (TUJ-1) apoptosis (Caspase-3, BAX), and reduced axonal degeneration while promoting myelin (MBP) regeneration, indicating a neuroprotective effect. These findings are linked to the activation of the AKT/mTOR signaling pathway. Plasmalogens reduce ROS levels and regulate inflammation-induced damage, contributing to neuroprotection. This study reveals that plasmalogens promote remyelination, reduce axonal degeneration and neuronal apoptosis, and-used here for the first time in spinal cord injury repair- may protect neurons by reducing ROS levels and activating the AKT/mTOR signaling pathway.

Neuroglial decline defines cognitive ageing

Neuroglia of the central nervous system, represented by astroglia, oligodendroglia and microglia, are fundamental for life-long support of homeostasis, plasticity and defence of the neural tissue. In particular neuroglial cells contribute to the cognitive reserve, which defines the neurological and cognitive outcome of both physiological and pathological ageing. Physiological ageing is accompanied with structural and functional decline of neuroglia. In particular, astrocytes undergo morphological atrophy and functional asthenia which compromises their vital functions such as glutamate clearance, K+ buffering and synaptic support. Old oligodendrocytes lose their myelination capacity, which results in the thinning of myelin sheath and atrophy of white matter. Finally, ageing is associated with accumulation of dystrophic microglia which limits neuroprotection. Age-dependent neuroglial decline impedes cognitive reserve, contributes to cognitive impairment, and increases vulnerability of the nervous system to neurodegeneration. Life style changes positively impact on neuroglial structure and function this improving cognitive longevity. Keywords: ageing; cognitive longevity; neuroglia, astroglia, oligodendroglia; oligodendroglial precursor cells; microglia

Hypomyelinating Leukodystrophy 14 (HLD14)-Related UFC1 p.Arg23Gln Decreases Cell Morphogenesis: A Phenotype Reversable with Hesperetin.

In the central nervous system (CNS), proper interaction between neuronal and glial cells is crucial for the development of mature nervous tissue. Hypomyelinating leukodystrophies (HLDs) are a group of genetic CNS disorders characterized by hypomyelination and/or demyelination. In these conditions, genetic mutations disrupt the biological functions of oligodendroglial cells, which are responsible for wrapping neuronal axons with myelin sheaths. Among these, an amino acid mutation of the ubiquitin-fold modifier conjugating enzyme 1 (UFC1) is associated with HLD14-related disease, characterized by hypomyelination and delayed myelination in the brain. UFC1 is a critical component of the UFMylation system, functioning similarly to E2-conjugating enzymes in the ubiquitin-dependent protein degradation system. We describe how a missense mutation in UFC1 (p.Arg23Gln) leads to the aggregation of UFC1 primarily in lysosomes in FBD-102b cells, which are undergoing oligodendroglial cell differentiation. Cells with mutated UFC1 exhibit reduced Akt kinase phosphorylation and reduced expression of differentiation and myelination marker proteins. Consistently, these cells exhibit impaired morphological differentiation with a reduced ability to extend widespread membranes. Interestingly, hesperetin, a citrus flavonoid with known neuroprotective properties, was found to restore differentiation abilities in cells with the UFC1 mutation. These findings indicate that the HLD14-related mutation in UFC1 causes its lysosomal aggregation, impairing its morphological differentiation. Furthermore, the study highlights potential therapeutic insights into the pathological molecular and cellular mechanisms underlying HLD14 and suggests hesperetin as a promising candidate for treatment.

Establishment and Validation of the Diagnostic Value of Oligodendrocyte-related Genes in Alzheimer's Disease.

AD is a demyelinating disease. Myelin damage initiates the pathological process of AD, resulting in abnormal synaptic function and cognitive decline. The myelin sheath formed by oligodendrocytes (OL) is a crucial component of white matter. Investigating AD from the perspective of OL may offer novel diagnostic and therapeutic perspectives. This study aimed to analyze the association between OL-related genes and Alzheimer's disease (AD) using bioinformatics and verify this association via molecular biology experiments. The AD datasets were acquired from the Gene Expression Omnibus (GEO) database of NCBI. Consensus clustering was employed to determine the subtypes of AD, followed by evaluating the clinical characteristics of these subtypes. Subsequently, immune infiltration analysis of relevant genes and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identify modules and hub genes associated with AD progression. The intersection of genes obtained was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. To narrow down the scope and identify OL-related genes with diagnostic potential, three machine learning algorithms were utilized. In addition, the eXtreme Sum (XSum) algorithm was used to screen small molecule drug candidates based on the connectivity map (CMAP) database. Finally, these identified genes were validated using Real-time fluorescence quantitative PCR (RT-qPCR). Among the three subtypes of AD, Cluster A and Cluster C exhibited increased levels of Braak and neurofibrillary tangles compared to Cluster B. The proportion of females was greater than that of males among the three subclasses of AD. There were no significant differences in age among the three subclasses, but significant differences in gene expression existed. Through WGCNA analysis, 108 genes were identified. Among these, 16 genes were identified as shared genes by the least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machines (SVM) algorithms, and logistic regression further determined 11 genes. The establishment of a nomogram demonstrated the significance of these 11 genes in AD. The "XSum" algorithm revealed five drugs with therapeutic potential for AD. qPCR analysis revealed the upregulation and downregulation of the highlighted genes. According to this study, 11 genes related to OL were also found to be associated with immune cell infiltration in AD patients. These genes demonstrated potential diagnostic value for AD. Additionally, we screened five small molecular drugs that exhibit potential therapeutic effects on AD. This research provides a new perspective for personalized clinical management and treatment of AD.

Recommendations of Multiple Sclerosis and Neuroimmunology Section of Polish Neurological Society and Immuno-oncology Section of Polish Society of Oncology on oncological risk in patients with multiple sclerosis undergoing immunomodulatory therapy.

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS) that is usually diagnosed between the ages of 20 and 40. Changes in the immune system also observed in cancer may suggest a higher prevalence of cancer in the MS patient population. In recent years, many highly effective immunosuppressive drugs have been introduced into disease-modifying therapy (DMT) which may be associated with a higher risk of cancer development in patients with MS. This paper presents current data on the oncological risk of individual drugs. In addition, it provides recommendations on the management for qualifying for DMT and monitoring the safety of the therapy from anoncological perspective.

Suspected fenugreek (Trigonella foenum-graecum L.) toxicosis in a herd of Saskatchewan beef cattle.

An apparent outbreak of fenugreek forage toxicosis occurred in a beef cattle herd near Moose Jaw, Saskatchewan in February-May 2022. The herd had consumed fenugreek hay from late fall to early winter. Clinical signs included various degrees of weakness, ataxia, knuckling, walking on hocks, and recumbency. All adult cattle in the herd eventually died or were euthanized. Feed analysis did not reveal nutritional deficiencies or mycotoxin contamination. Liver mineral and vitamin status of affected animals did not indicate any consistent abnormality. The last live cow in the herd was presented to a veterinary teaching hospital for evaluation and subsequent postmortem examination. Major postmortem findings included emaciation, and sciatic nerve and spinal cord axonal degeneration. Histologic examination of the sciatic nerve showed Wallerian-like axonal degeneration, increased Schwann cell nuclei, and endoneurial fibrosis. Histologic examination of the spinal cord showed infrequent myelin sheath dilation and digestion chambers within white matter. These results are consistent with other reports of natural and experimental outbreaks of fenugreek poisoning in livestock. To our knowledge, fenugreek toxicosis has not been reported previously in Canada. We conclude that caution should be taken when feeding fenugreek hay to cattle.

Single-Cell Multi-omics Assessment of Spinal Cord Injury Blocking via Cerium-doped Upconversion Antioxidant Nanoenzymes.

Spinal cord injury (SCI) impairs the central nervous system and induces the myelin-sheath-deterioration because of reactive oxygen species (ROS), further hindering the recovery of function. Herein, the simultaneously emergency treatment and dynamic luminescence severity assessment (SETLSA) strategy is designed for SCI based on cerium (Ce)-doped upconversion antioxidant nanoenzymes (Ce@UCNP-BCH). Ce@UCNP-BCH can not only efficiently eliminate the SCI localized ROS, but dynamically monitor the oxidative state in the SCI repair process using a ratiometric luminescence signal. Moreover, the classic basso mouse scale score and immunofluorescence analysis together exhibit that Ce@UCNP-BCH effectively facilitates the regeneration of spinal cord including myelin sheath, and promotes the functional recovery of SCI mice. Particularly, the study combines snATAC-eq and snRNA-seq to reveal the heterogeneity of spinal cord tissue following Ce@UCNP-BCH treatment. The findings reveal a significant increase in myelinating oligodendrocytes, as well as higher expression of myelination-related genes, and the study also reveals the gene regulatory dynamics of remyelination after treatment. Besides, the ETLSA strategy synergistically boosts ROS consumption through the superoxide dismutase (SOD)-related pathways after SOD-siRNA treatment. In conclusion, this SETLSA strategy with simultaneously blocking and dynamic monitoring oxidative stress has enriched the toolkit for promoting SCI repair.

Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice

As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change. Furthermore, disrupted proliferation of oligodendrocyte precursor cells (OPCs) contributes to repeated sevoflurane exposure-induced myelin defect. This may be owing to an accumulated tuberous sclerosis complex 1 (TSC1) expression and inhibition of mammalian target of rapamycin (mTOR) signaling, leading to the unbalance of TSC1-mTORC1 activity after repeated sevoflurane exposure, which is critical for proper myelination of the central nervous system (CNS). Moreover, repeated sevoflurane exposure aggregates myelination defect in the cuprizone-induced demyelination model. Together, our present work establishes the role of sevoflurane exposure in myelin integrity in the PFC of the adult male mice and provides a new insight to elucidate the mechanism of GAs-induced brain dysfunctions.

Quantitative magnetization transfer and g-ratio imaging of white matter myelin in early psychotic spectrum disorders.

Myelin abnormalities in white matter have been implicated in the pathophysiology of psychotic spectrum disorders (PSD), which are characterized by brain dysconnectivity as a core feature. Among evidence from in vivo MRI studies, diffusion imaging findings have largely supported disrupted white matter integrity in PSD; however, they are not specific to myelin changes. Using a multimodal imaging approach, the current study aimed to further delineate myelin and microstructural changes in the white matter of a young PSD cohort. We utilized quantitative magnetization transfer (qMT) imagingcombined with advanced diffusion imaging to estimate specific myelin-related biophysical properties in 51 young adult PSD patients compared with 38 age-matched healthy controls. The macromolecular proton fraction (MPF) obtained from qMT was used as a specific marker of myelin content. Additionally, MPF was employed along with diffusion metrics of axonal density (vic) and extra-cellular volume fraction to derive the g-ratio, a measure of relative myelin sheath thickness defined as the ratio of inner to outer axonal diameter. Compared to controls, we observed a widespread MPF reduction and localized g-ratio increase in patients, primarily those with a diagnosis of schizophrenia or depressive schizoaffective disorder. No between-group differences were noted in vic, suggesting similar axonal densities across groups. Correlation analysis revealed that lower MPF was significantly related to poorer working memory performance in PSD, while the HC group showed a positive association for working memory with both g-ratio and vic. The pattern of changes observed in our multimodal imaging markers suggests that PSD, depending on symptomatology, is characterized by specific alterations in white matter integrity and myelin-axonal geometry of major white matter tracts, which may impact working memory function. These findings provide a more detailed view of myelin-related white matter changes in early stages of PSD.

Cholesterol Metabolism in CNS Diseases: The Potential of SREBP2 and LXR as Therapeutic Targets.

The brain is the organ with the highest cholesterol content in the body. Cholesterol in the brain plays a crucial role in maintaining the integrity of synapses and myelin sheaths to ensure normal brain function. Disruptions in cholesterol metabolism are closely associated with various central nervous system (CNS) diseases, including Alzheimer's disease (AD), Huntington's disease (HD), and multiple sclerosis (MS). In this review, we explore the synthesis, regulation, transport, and functional roles of cholesterol in the CNS. We discuss in detail the associations between cholesterol homeostasis imbalance and CNS diseases including AD, HD, and MS, highlighting the significant role of cholesterol metabolism abnormalities in the development of these diseases. Sterol regulatory element binding protein-2 (SREBP2) and liver X receptor (LXR) are two critical transcription factors that play central roles in cholesterol synthesis and reverse transport, respectively. Their cooperative interaction finely tunes the balance of brain cholesterol metabolism, presenting potential therapeutic value for preventing and treating CNS diseases. We particularly emphasize the alterations in SREBP2 and LXR under pathological conditions and their impacts on disease progression. This review summarizes current therapeutic agents targeting these two pathways, with the hope of broadening the perspectives of CNS drug developers and encouraging further study into SREBP2 and LXR-related therapies for CNS diseases.

Evolutionary origins of synchronization for integrating information in neurons.

The evolution of brain-expressed genes is notably slower than that of genes expressed in other tissues, a phenomenon likely due to high-level functional constraints. One such constraint might be the integration of information by neuron assemblies, enhancing environmental adaptability. This study explores the physiological mechanisms of information integration in neurons through three types of synchronization: chemical, electromagnetic, and quantum. Chemical synchronization involves the diffuse release of neurotransmitters like dopamine and acetylcholine, causing transmission delays of several milliseconds. Electromagnetic synchronization encompasses action potentials, electrical gap junctions, and ephaptic coupling. Electrical gap junctions enable rapid synchronization within cortical GABAergic networks, while ephaptic coupling allows structures like axon bundles to synchronize through extracellular electromagnetic fields, surpassing the speed of chemical processes. Quantum synchronization is hypothesized to involve ion coherence during ion channel passage and the entanglement of photons within the myelin sheath. Unlike the finite-time synchronization seen in chemical and electromagnetic processes, quantum entanglement provides instantaneous non-local coherence states. Neurons might have evolved from slower chemical diffusion to rapid temporal synchronization, with ion passage through gap junctions within cortical GABAergic networks potentially facilitating both fast gamma band synchronization and quantum coherence. This mini-review compiles literature on these three synchronization types, offering new insights into the physiological mechanisms that address the binding problem in neuron assemblies.

Exercise therapy facilitates neural remodeling and functional recovery post-spinal cord injury via PKA/CREB signaling pathway modulation in rats.

Neuronal structure is disrupted after spinal cord injury (SCI), causing functional impairment. The effectiveness of exercise therapy (ET) in clinical settings for nerve remodeling post-SCI and its underlying mechanisms remain unclear. This study aims to explore the effects and related mechanisms of ET on nerve remodeling in SCI rats. We randomly assigned rats to various groups: sham-operated group, sham-operated + ET, SCI alone, SCI + H89, SCI + ET, and SCI + ET + H89. Techniques including motor-evoked potential (MEP), video capture and analysis, the Basso-Beattie-Bresnahan (BBB) scale, western blotting, transmission electron microscopy, hematoxylin and eosin staining, Nissl staining, glycine silver staining, immunofluorescence, and Golgi staining were utilized to assess signal conduction capabilities, neurological deficits, hindlimb performance, protein expression levels, neuron ultrastructure, and tissue morphology. H89-an inhibitor that targets the protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway-was employed to investigate molecular mechanisms. This study found that ET can reduce neuronal damage in rats with SCI, protect residual tissue, promote the remodeling of motor neurons, neurofilaments, dendrites/axons, synapses, and myelin sheaths, reorganize neural circuits, and promote motor function recovery. In terms of mechanism, ET mainly works by mediating the PKA/CREB signaling pathway in neurons. Our findings indicated that: (1) ET counteracted the H89-induced suppression of the PKA/CREB signaling pathway following SCI; (2) ET significantly alleviated neuronal injury and improved motor dysfunction; (3) ET facilitated neuronal regeneration by mediating the PKA/CREB signaling pathway; (4) ET enhanced synaptic and dendritic spine plasticity, as well as myelin sheath remodeling, post-SCI through the PKA/CREB signaling pathway.

Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.

Oligodendrocytes, the myelinating cells in the central nervous system, are implicated in several neurological disorders marked by dysfunctional RNA-binding proteins (RBPs). The present study aimed at investigating the role of hnRNP A1 in the proteome of the corpus callosum, prefrontal cortex, and hippocampus of a murine cuprizone-induced demyelination model. Right after the cuprizone insult, we administered an hnRNP A1 splicing activity inhibitor and analyzed its impact on brain remyelination by nanoESI-LC-MS/MS label-free proteomic analysis to assess the biological processes affected in these brain regions. Significant alterations in essential myelination proteins highlighted the involvement of hnRNP A1 in maintaining myelin integrity. Pathways related to sphingolipid and endocannabinoid signaling were affected, as well as the synaptic vesicle cycle and GABAergic synapses. Although behavioral impairments were not observed, molecular changes suggest potential links to memory, synaptic function, and neurotransmission processes. These findings enhance our understanding of the multifaceted roles of hnRNP A1 in the central nervous system, providing valuable insights for future investigations and therapeutic interventions in neurodegenerative and demyelinating diseases.

Anterior bilateral optic neuritis as a complication of Varicella‐Zoster virus (VZV)

Aims/Purpose: To shed light on optic neuritis as a potential ocular complication of Varicella‐Zoster virus (VZV) infection.Methods: Presentation of a clinical case.Results: We present the case of a 70‐year‐old woman, who arrived at the Emergency Room complaining of a bilateral acute loss of visual acuity. She had received treatment on several occasions for a recurring zoster involving the left V2 territory, the last episode being one month before her visit. She had a visual acuity of 0.3 on her right eye, and 0.6 on her left eye. Pupil examination evidenced a relative afferent pupillary defect (RAPD) on her right eye. Dyschromatopsia was documented by red desaturation and Ishihara tests. Fundus examination displayed an asymmetrical bilateral papillitis, predominant in her right eye. This finding was confirmed by an Optic Coherence Tomography (OCT). A cranial CT scan and a general blood analysis were performed, and both returned normal results. The patient was admitted to the Hospital to start treatment with intravenous steroids. Additional tests were performed, including blood serological tests, a temporal artery Doppler ultrasound, a cranial MRI, and a lumbar puncture. Blood serological tests showed positive high titles of IgG VZV, and came back negative for IgM VZV. Lastly, the polymerase chain reaction (PCR) test on the CSF sample turned out positive for VZV, shedding light on the diagnosis. Steroids were suspended and the patient was started on intravenous Acyclovir. Clinical evolution was favorable, and her visual acuity on the 2‐month follow‐up visit had climbed up to 0.6 on her right eye and 0.7 on her left eye.Conclusions: This case illustrates the relevance of ruling out infectious causes of optic neuritis, specifically VZV, in patients in which other causes are less likely, those who present a bad evolution on inflammatory treatment, or who have a recent episode of VZV infection. MRI demyelination is a frequent finding in both demyelinating and infectious diseases, therefore not ruling out the latter. Positive blood serology indicates previous contact with VZV, but has little sensibility for detecting an active infection. All these reasons justify the need to select patient who may benefit of a lumbar puncture, as an early diagnosis radically changes the therapeutical approach.