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Brain Proteome-Wide and Transcriptome-Wide Asso-ciation Studies, Bayesian Colocalization, and Mendelian Randomization Analyses Reveal Causal Genes of Parkinson's Disease.

How genome-wide associated loci confer risk for Parkinson's disease is unclear. We aim to reveal causal genes through effects on brain prote … tent with transcriptomic evaluations. CD38 and GPNMB were preferentially enriched in astrocytes and oligodendrocyte precursor cells, respectively. And CD38 and GPNMB were suggested to be the targets of many oncological drugs from Drug-Gene Interaction database. In conclusion, utilizing multidimensional data, GPNMB and CD38 were prioritized as the causal genes of Parkinson's dise …

Myelin modifications after chronic sleep loss in adolescent mice.

STUDY OBJECTIVES: Previous studies found that sleep loss can suppress the expression of genes implicated in myelination and can have adverse effects on oligodendrocyte precursor cells. On the other hand, sleep may favor myelination by promoting the expression of genes involved in its formation and maintenance. Albeit limited, these results suggest that sleep loss can have detrimental effects on the formation and maintenance of myelin. METHODS: Here, we tested this hypothesis by evaluating ultrastructural modifications of myelin in two brain regions (corpus callosum and lateral olfactory tract…

Genetic background modulates the effect of glucocorticoids on proliferation, differentiation and myelin formation of oligodendrocyte lineage cells.

Anxiety disorders are prevalent mental disorders. Their predisposition involves a combination of genetic and environmental risk factors, such as psychosocial stress. Myelin plasticity was recently associated with chronic stress in several mouse models. Furthermore, we found that changes in both myelin thickness and node of Ranvier morphology after chronic social defeat stress are influenced by the genetic background of the mouse strain. To understand cellular and molecular effects of stress-associated myelin plasticity, we established an oligodendrocyte (OL) model consisting of OL primary cell

NSUN5 Deficiency Drives Anxiety-Like Behaviors in Mice via Increased Microglial Activation and Impaired LTD Induction in the Basolateral Amygdala.

Williams-Beuren Syndrome (WBS), is a neurodevelopmental disorder characterized by anxiety, hypersociality and neurocognitive abnormalities, … rs without hypersociality in both adult male and female mice. NSUN5 exhibits specific expression in oligodendrocyte precursor cells (OPCs) within the basolateral amygdala (BLA), which is one of the main brain regions linked to anxiety. In addition, NSUN5 deficiency in mice leads to reduced OPCs proliferation accompanied with microglial activation. Mechanistically, we revealed th …

Near infrared light reduces oxidative stress and preserves function in CNS tissue vulnerable to secondary degeneration following partial transection of the optic nerve.

Traumatic injury to the central nervous system (CNS) is accompanied by the spreading damage of secondary degeneration, resulting in further … ing partial injury. The WARP 10 NIR light treatment also prevented increases in NG-2-immunopositive oligodendrocyte precursor cells (OPCs) that occurred in ventral ON as a result of partial ON transection. Importantly, normal visual function was restored by NIR light treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and the Y-maze pattern discriminati …

Rosiglitazone alleviates white matter injury by inhibiting NLRP3/capspase-1 mediated microglial pyroptosis via downregulating KLF4.

White matter injury (WMI) is a critical pathological feature of various neurological disorders. Microglial pyroptosis, a form of inflammator … re significantly suppressed by ROSI. ROSI also reduced LPS/ATP-induced injury in co-cultured MO3.13 oligodendrocyte precursor cells (OPCs), improving cell viability and reducing apoptosis. In direct-treatment experiments, ROSI did not significantly affect MO3.13 cell viability, supporting an indirect protective effect on OPCs. Mechanistically, ROSI downregulated KLF4, a transcri …

Олигодендроглиевые клетки-прекурсоры модифицируют иммунную реакцию и раннее обезвоживание в муслиновой модели множественного склероза.

Возрождение патофизиологии множественного склероза человека (MS) в моделях животных имеет решающее значение для выявления механизмов, спровоцирующих демиэлизацию, и разработки стратегий раннего вмешательства. Здесь мы стремились моделировать чрезмерно активированный Wnt (место беспутной интеграции), сигнализирующий ранее в посмертных тканях мозга пациентов с MS путем создания экспериментального аутоиммунного энцефаломиелита (EAE) в PdgfraCreER; Apcfl/fl и Olig2Cre; Apcfl/fl мыши. Эти мыши перегружены сигнализацией Wnt в клетках-прекурсорах олигодендроцитах (OPC) из-за условного выруба аденомат

Совпадение в аннотации оригинала
Reproducing the pathophysiology of human multiple sclerosis (MS) in animal models is critical to identifying mechanisms triggering demyelina … in PdgfraCreER;Apcfl/fl and Olig2Cre;Apcfl/fl mice. These mice have overactivated Wnt signaling in oligodendrocyte precursor cells (OPCs) because of a conditional knockout of the pathway repressor adenomatous polyposis coli (APC). PdgfraCreER;Apcfl/fl EAE mice exhibited increased expression of markers for Wnt activation such as Axis inhibition protein 2 (AXIN2) and Wnt inhibito …

Protective effects of 4-aminopyridine in experimental optic neuritis and multiple sclerosis.

Chronic disability in multiple sclerosis is linked to neuroaxonal degeneration. 4-aminopyridine (4-AP) is used and licensed as a symptomatic … nglion cells. Rather, histology and in vitro experiments indicated 4-AP stabilization of myelin and oligodendrocyte precursor cells associated with increased nuclear translocation of the nuclear factor of activated T cells. In experimental optic neuritis, 4-AP potentiated the effects of immunomodulatory treatment with fingolimod. As extended release 4-AP is already licensed for …

Sodium Butyrate, a Histone Deacetylase Inhibitor, Exhibits Neuroprotective/Neurogenic Effects in a Rat Model of Neonatal Hypoxia-Ischemia.

Neonatal hypoxic-ischemic (HI) injury still remains an important issue as it is a major cause of neonatal death and neurological dysfunction … by HI. Moreover, the application of this HDACi protected against HI-induced loss of neuroblasts and oligodendrocyte precursor cells, as well as against neuroinflammation. The observed neuroprotective action suggests that SB may serve as a potential candidate for future treatment of HI-evoked injury in neonates.

Zika virus cell tropism in the developing human brain and inhibition by azithromycin.

The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital Z … cing viral proliferation. In the brain, ZIKV preferentially infected neural stem cells, astrocytes, oligodendrocyte precursor cells, and microglia, whereas neurons were less susceptible to infection. These findings suggest mechanisms for microcephaly and other pathologic features of infants with congenital ZIKV infection that are not explained by neural stem cell infection alone …

Increased expression of gamma-aminobutyric acid transporters GAT-1 and GAT-3 in the spinal trigeminal nucleus after facial carrageenan injections.

The present study aimed to elucidate the distribution of gamma-aminobutyric acid (GABA) transporters in the spinal trigeminal nucleus after … others lacked glial filaments, and contained dense marginated heterochromatin, and had features of oligodendrocyte precursor cells. An increase in immunoreactivity to both transporters was observed on the injected but not the contralateral side 3 days after facial carrageenan injections. In rats given three further weekly injections of carrageenan and killed 3 days after the fo …

From Natural Compound Screening to Myelin-Associated Effects: Identification of Morusin as a Potent Promoter of Oligodendrocyte Differentiation.

Myelination is essential for rapid axonal conduction and neuronal integrity, and its loss in demyelinating diseases such as multiple sclerosis (MS) leads to progressive neurological impairment. Despite advances in immunomodulatory therapies, effective strategies that promote remyelination remain limited. Here, we identify Morusin, a prenylated flavonoid natural compound, as a potent enhancer of oligodendrocyte (OL) differentiation and myelination-associated outcomes. Using a fluorescence-based screen of diverse flavonoids in primary rat oligodendrocyte progenitor cells (OPCs), it was found tha

The Myelin-Derived Peptide NSDP1 Suppresses Neuroinflammation and Attenuates Demyelination in Chronic Cuprizone-Fed Mice via Modulation of cGAS-STING Signaling.

Multiple sclerosis (MS) is characterized by demyelination and neuroinflammation. In a cuprizone (CPZ)-induced demyelination mouse model, proteomic analysis revealed the significant downregulation of a myelin basic protein-derived peptide (sequence: DTGILDSIGRFFS), which we have designated as NSDP1 (nervous system-derived peptide 1). In vitro, NSDP1 suppressed LPS-induced microglial activation in BV2 cells, reducing reactive oxygen species (ROS) production, downregulating pro-inflammatory markers (iNOS, TNF-α, IL-1β), and upregulating the expression of anti-inflammatory marker Arg-1. In vivo, N

Ceruloplasmin-deficient mice show changes in PTM profiles of proteins involved in messenger RNA processing and neuronal projections and synaptic processes.

Ceruloplasmin (Cp) is a multicopper oxidase with ferroxidase properties being of importance to the mobilisation and export of iron from cell … regulated proteins, glycoproteins and phosphoproteins appeared mostly to be located to neurons and oligodendrocyte precursor cells. Cp deficiency especially affected the function of proteins involved in the extension of neuronal projections, synaptic signalling and cellular mRNA processing and affected the expression of proteins involved in neurodegenerative disease and diabete …

Neural cells generated from human induced pluripotent stem cells as a model of CNS involvement in mucopolysaccharidosis type II.

Mucopolysaccharidosis type II (MPSII) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene (IDS, Xq28). MPSII is characterized by skeletal deformities, hearing loss, airway obstruction, hepatosplenomegaly, cardiac valvular disease, and progressive neurological impairment. At the cellular level, IDS deficiency leads to lysosomal storage of glycosaminoglycans (GAGs), dominated by accumulation of dermatan and heparan sulfates. Human induced pluripotent stem cells (iPSC) represent an alternative system that complements the available MPSII murine

Spinal implantation of hNT neurons and neuronal precursors: graft survival and functional effects in rats with ischemic spastic paraplegia.

Transient spinal ischemia, a complication associated with aortic cross-clamp may lead to spastic paraplegia. Once fully developed this deficit is permanent. Quantitative histopathological assessments and pharmacological studies show that the ischemic spasticity is secondary to the loss of lumbar GABA and glycinergic inhibitory interneurons. In the present study, we investigated whether human hNT neurons or committed Sprague-Dawley rat spinal neuronal precursors (SNPs) when grafted into previously ischemic spinal segments depleted of inhibitory neurons would restore local inhibitory tone and am

Genetic, cellular, and connectomic characterization of the brain regions commonly plagued by glioma.

For decades, it has been known that gliomas follow a non-random spatial distribution, appearing more often in some brain regions (e.g. the i … nectedness. Brain regions populated with putative cells of origin for glioma, neural stem cells and oligodendrocyte precursor cells, exhibited a high glioma frequency. Leveraging a human brain atlas of post-mortem gene expression, we found that gliomas were localized to brain regions enriched with expression of genes associated with chromatin organization and synaptic signalling …

Neuroinflammation, Microglia and Implications for Retinal Ganglion Cell Survival and Axon Regeneration in Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) refers to a pathological condition caused by a direct or indirect insult to the optic nerves, which often l … isual function recovery after ONC. Activated retinal microglia is required for the proliferation of oligodendrocyte precursor cells (OPCs); however, sustained activation of retinal microglia suppress the differentiation of OPCs into mature oligodendrocytes for remyelination after injury. Collectively, controlled activation of retinal microglia and infiltrating myeloid cells faci …

Expression patterns of prosaposin and its receptors, G protein-coupled receptor (GPR) 37 and GPR37L1 mRNAs, in the chick inner ear.

Prosaposin is a glycoprotein that is widely conserved in vertebrates. It serves as a precursor for saposins A, B, C, and D, which are necessary activators of lysosomal sphingolipid hydrolases. It can also act as a neurotrophic factor. Prosaposin plays a crucial role in the mammalian vestibuloauditory system because it prevents progressive deafness and severe vestibular dysfunction. Prosaposin can exhibit a neurotrophic effect through the G protein-coupled receptor (GPR), and GPR37 and GPR37L1 are its candidate receptors. In this study, we examined the expression patterns of prosaposin, GPR37,

Glial Cells in Alzheimer's Disease: Pathogenic Mechanisms and Therapeutic Frontiers.

The rising incidence of brain diseases parallels the global trend of an aging population, with Alzheimer's disease (AD) being a leading neurodegenerative disorder characterized by memory loss, dementia, and cognitive decline. Despite extensive research, current treatments for AD remain largely symptomatic and have had limited success in halting disease progression, thereby shifting attention toward glial cells as promising therapeutic targets due to their emerging roles in AD pathogenesis. Astrocytes are involved in both beneficial and pathological processes in AD, such as cytokine secretion,