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Enhanced re-myelination in transthyretin null mice following cuprizone mediated demyelination.

Thyroid hormones (THs) impact nearly every tissue in the body, including the adult and developing central nervous system. The distribution of THs around the body is facilitated by specific TH distributor proteins including transthyretin (TTR). In addition to being produced in the liver, TTR is synthesized in the choroid plexus of the brain. The synthesis of TTR by choroid plexus epithelial cells allows transport of THs from the blood into the brain. Adequate supply of THs to the brain is required for developmental myelination of axons and the maintenance of mature myelin throughout adult life,

Glucagon-Like Peptide-1 Receptor Agonists as Potential Myelination-Inducible and Anti-Demyelinating Remedies.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) were developed as insulinotropic and anti-hyperglycemic agents for the treatment of typ … rticle, we describe the potential efficacy of GLP-1RAs for the induction of axonal regeneration and remyelination following nerve lesions and the prevention and alleviation of demyelinating disorders, particularly multiple sclerosis.

Подстегнутая стрессом связь с нанотрубкой в глиальных клетках CNS: последствия провокационного демиэлирования и отказа в ремонте.

Множественные склерозы и связанные с ними воспалительные расстройства центральной нервной системы, включая расстройство спектра нейромиелита, расстройство спектра и болезнь миэлина олигодендроцита гликопротеина, связанные с антителами, характеризуются повреждениями имунной ткани, глиальной дисфункцией, метаболическим стрессом и неполным ремонтом. Хотя периферическая иммунная инфильтрация и антителные механизмы объясняют многие аспекты образования острых повреждений, они не в полной мере учитывают стойкую активность повреждения, метаболическую нестабильность или отказ от ремиэлирования в местно

Совпадение в аннотации оригинала
Multiple sclerosis and related inflammatory demyelinating disorders of the central nervous system, including neuromyelitis optica spectrum d … sion formation, they do not fully account for persistent lesion activity, metabolic instability, or remyelination failure within the local tissue microenvironment. Tunneling nanotubes are thin, actin-rich membranous connections that enable direct intercellular transfer of organelles, vesicles, proteins, ions, and stress-related cargoes. In the nervous system, t …

A gelatin methacryloyl (GelMA)-based biomimetic melatonin/vascular endothelial growth factor-encoding plasmid (pVEGF) nerve conduit regulates the early redox-angiogenic microenvironment for long-gap peripheral nerve repair.

Biological macromolecule-derived matrices and biomimetic delivery interfaces can convert artificial nerve conduits from passive bridges into locally regulatory repair platforms. Long-gap peripheral nerve defects remain difficult to repair because the defect region must rapidly rebuild a vascularized, cytoprotective, and cell-permissive microenvironment for Schwann cell survival, axonal extension, and remyelination. Here, we developed a Gelatin Methacryloyl (GelMA)-based biomimetic melatonin/vascular endothelial growth factor (VEGF)-encoding plasmid DNA (pVEGF) Polycaprolactone (PCL)/GelMA nerv…

Построение олигодендроцитов, подобных прекурсорам, из эмбриональных фибробатластов мыши с использованием miR-7a Имитация.

ЦЕЛИ: Разработка эффективных стратегий повышения эффективности мер по ликвидации последствий по-прежнему является одной из основных терапевтических проблем в связи с такими демиелинизирующими расстройствами, как множественный склероз (МС). МикроРНК (миРНК) стали мощным регулятором клеточной судьбы. Было показано, что miR-7a , в значительной степени выражается в олигодендроцитных клетках-прекурсорах (ОПК). Цель этого исследования заключалась в изучении вопроса о том, является ли завышенное выражение мнений miR-7a :: может перепрограммировать эмбриональные фибробатласты мыши (МЭФ) в похожие на O

Совпадение в аннотации оригинала
OBJECTIVES: Developing effective strategies to enhance remyelination remains a major therapeutic challenge in demyelinating disorders such as multiple sclerosis (MS). MicroRNAs (miRNAs) have emerged as powerful regulators of cell fate. It has been shown that miR-7a is highly expressed in oligodendrocyte precursor cells (OPCs). This study aimed to investigate…

Curcumin-Piperine Self-Nanoemulsifying Delivery in Zanthoxylum rhetsa Seed Oil Attenuates Cuprizone-Induced Frontal Cortex Toxicity.

Background/Objectives: Demyelination and neuroinflammation are central features of multiple sclerosis (MS), contributing to motor deficits a … ction. MBP levels were highest in PFZ-treated mice, surpassing control values and indicating strong remyelination potential. These improvements persisted and further advanced at week 7, especially in PFZ and CFZ groups. Conclusions: Curcumin-based SNEDDS, particularly PFZ, significantly mitigated CPZ-induced neuroinflammation, promoted remyelination, and restor …

Minocycline Ameliorates Depressive-Like Behavior and Demyelination Induced by Transient Global Cerebral Ischemia by Inhibiting Microglial Activation.

Global cerebral ischemia (GCI) commonly occurs in the elderly. Subcortical white matter lesions and oligodendrocyte (OLG) loss caused by cerebral ischemia have been implicated in the development of post-ischemic depression and cognitive impairment. OLGs are necessary for axonal myelination; the disrupted differentiation of OLG progenitor cells (OPCs) is associated with impaired remyelination. Evidence has indicated that increased levels of inflammatory cytokines released from activated microglia induce depression-like behaviors by affecting neurotransmitter pathways, but the mechanisms remain …

Oct4 transcription factor in conjunction with valproic acid accelerates myelin repair in demyelinated optic chiasm in mice.

Multiple sclerosis is a demyelinating disease with severe neurological symptoms due to blockage of signal conduction in affected axons. Spontaneous remyelination via endogenous progenitors is limited and eventually fails. Recent reports showed that forced expression of some transcription factors within the brain converted somatic cells to neural progenitors and neuroblasts. Here, we report the effect of valproic acid (VPA) along with forced expression of Oct4 transcription factor on lysolecithin (LPC)-induced experimental demyelination. Mice were gavaged with VPA for one week, and then inducib…

Acetyl-l-carnitine enhances myelination of regenerated fibers of the lateral olfactory tract.

It is well known that acetyl-l-carnitine (ALC) has various neuroprotective effects against neurodegenerative diseases. In addition, it has been reported that ALC facilitates myelination of regenerated axons after peripheral nerve injuries. We previously reported that spontaneous regeneration of the lateral olfactory tract (LOT), the main fiber tract of the central olfactory system, consistently occurred in newborn rats and a majority of these regenerated fibers were unmyelinated in neonatally LOT-transected young adult rats. To investigate the effects of ALC treatment on myelination in LOT, ne

Pathophysiology and Repair Potential in Degenerative Cervical Myelopathy.

Degenerative cervical myelopathy (DCM) is a chronic spinal cord disorder caused by progressive compression leading to ischemia, cell death, … of perfusion and plasticity. Adjunctive strategies, including neuroprotection, neuromodulation, and remyelination therapies, with rehabilitation, represent promising approaches to enhance recovery by targeting residual neural circuits and the evolving repair environment.

Opposing and potentially antagonistic effects of BMP and TGF-β in multiple sclerosis: The "Yin and Yang" of neuro-immune Signaling.

Bone Morphogenetic Proteins (BMP) and Transforming Growth Factor-beta (TGF-β) are cytokines with similar receptors and messengers. They are important for immune cell function, with BMPs exerting mainly proinflammatory but also anti-inflammatory effects, and TGF-β suppressing inflammation. Patients with Multiple Sclerosis exhibit BMP overactivity and suppressed TGF-β signaling. This dysregulated signaling participates in the crosstalk between infiltrating immune cells and glia, where BMP inhibits remyelination. Reciprocal antagonism between the two pathways takes place via a variety of mechanis…

Hypertrophic neuropathy with complete conduction block-- hereditary motor and sensory neuropathy type III.

Hypertrophic neuropathy is a non-specific consequence of repeated demyelination and remyelination, encountered in a wide range of inherited and acquired disorders. We report an 11-year-old boy with HMSN III, a kind of hypertrophic neuropathy, with clinical, electrophysiologic and pathologic data. The electrophysiologic studies show complete conduction block in the upper and lower extremities with severe abnormal spontaneous activities. The pathologic findings of sural nerve reveal prominent hypomyelination, onion bulb formation, and severe endoneurial collagenization. Complete conduction block…

Lysophosphatidyl choline-induced focal demyelination in the rabbit corpus callosum. Electron-microscopic observations.

Under electrophysiological control, a focal demyelinating lesion can be produced in the corpus callosum of the rabbit by slow pressure injection of a 1% solution of lysophosphatidyl choline (LPC). Light- and electron-microscopic examination of the LPC demyelinated corpus callosum indicates that many axons remain structurally intact after LPC injection. In addition, some axons show early signs of remyelination. Our results indicate that small diameter, central nervous system myelinated axons can be focally demyelinated with LPC. Furthermore, our procedure for producing demyelination in the corp…

Pathology of disulfiram neuropathy.

The pathological changes in a sural nerve biopsy from a 42-year-old woman with disulfiram-induced peripheral neuropathy were assessed by quantitative light microscopy, electron microscopy, and the study of teased nerve fibres. The nerve had a marked loss of myelinated fibres; of the remaining myelinated fibres some were undergoing Wallerian-type axonal degeneration. Large myelinated fibres were preferentially involved. Primary demyelination, remyelination, and evidence of regeneration were not present. Because of the marked differences between the pathological findings in disulfiram neuropathy…

Rhynchophylline inhibits cluster of differentiation 36 (CD36) on endothelial cells to reduce fibrotic scar formation and enhance functional recovery after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) causes severe neurological deficits due to extensive neurodegeneration and secondary pathological event … tological analyses were performed to examine functional recovery, vascular integrity, fibrosis, and remyelination. In vitro, bEnd.3 endothelial cells were exposed to IL-1β to induce inflammatory stress, and the effects of Rhy on CD36 expression, tight junction proteins, and trans-endothelial permeability were analyzed. Neuronal survival and neurite outgrowth as …

A Comprehensive Description of the Roadmap to Identify and Validate a Myelin Biomarker.

BACKGROUND: Demyelination and remyelination are major issues for scientists dealing with myelin disorders in both clinical and research fields. Despite that, rapid, reliable and convenient tools to monitor myelin changes still lack both in central and peripheral nervous system. Given that myelin is enriched in specific lipids and proteins, it is reasonable they could represent eligible candidates as structural damage biomarkers for this characteristic membrane. Among them, we focused on sphingomyelin (SM) due to the enrichment in myelin and because it is easily measurable in different biologic…

Arecoline alleviates autism spectrum disorder-like behaviors and cognition disorders in a valproic acid mouse model by activating the AMPK/CREB/BDNF signaling pathway.

Studies in humans have revealed that the pathogenesis of autism spectrum disorder (ASD) is linked to white matter abnormalities involving hy … expression of downstream BDNF, an essential neurotrophic factor for oligodendrocyte maturation and remyelination. These findings suggest that the AMPK/CREB/BDNF pathway may contribute to the therapeutic effects of arecoline, potentially through increased oligodendrocyte maturation and remyelination. This study provides preclinical evidence supporting arecoline …

Targeting Oligodendrocyte Dysfunction in Alzheimer's Disease: a New Frontier for Drug Repurposing with Antihistamines and Serotonin Receptor Agonists.

Emerging data highlight oligodendrocyte dysfunction and myelin degeneration as early contributors to the pathology of Alzheimer's disease (AD), questioning the conventional neuron-focused amyloid-tau model. This comprehensive review recapitulates both clinical and preclinical data linking oligodendrocytes (OLs) and oligodendrocyte precursor cells (OPCs) to amyloid-β secretion, accelerated cellular ageing, and loss of metabolic and trophic support. Simultaneously, microglial activation and neuroinflammation exacerbate damage to myelin and impair remyelination. High-field imaging technologies ar…

The transcription factor Stat-1 is essential for Schwann cell differentiation, myelination and myelin sheath regeneration.

BACKGROUND: Myelin sheath is a crucial accessory to the functional nerve-fiber unit, its disruption or loss can lead to axonal degeneration … n myelination. To test this, we used the following experiments: (1) In vivo, the effect of Stat1 on remyelination was observed in an in vivo myelination mode with Stat1 knockdown in sciatic nerves or specific knockdown in SCs. (2) In vitro, the RNA interference combined with cell proliferation assay, scratch assay, SC aggregate sphere migration assay, and a SC …

High phenylalanine concentrations induce demyelination and microglial activation in mouse cerebellar organotypic slices.

Phenylketonuria (PKU) is an inborn error of metabolism. Mutations in the enzyme phenylalanine hydroxylase (PAH)-encoding gene lead to a decr … exposure to a toxic concentration of Phe, a switch to the control medium for 7 days did not lead to remyelination, while very active remyelination was seen in slices following demyelination with lysolecithin. An enhanced number of microglia, displaying an activated type morphology, was seen after exposure of the slices to 2.4 mM Phe for 10 or 21 DIV. The result …