Результаты поиска

RAC1 regulates Sonic Hedgehog-medulloblastoma growth via GLI-mediated transcription.

BACKGROUND: Medulloblastoma (MB) is the most common malignant brain tumor of childhood, and current treatments cannot sufficiently inhibit t … 2661, transcript profiling, chromatin immunoprecipitation, and cytotoxicity assays in primary human astrocytes. We also determined the efficacy, brain penetration, and toxicity of GYS32661 in orthotopic spheroid Ptch1-/- mouse and rat models. RESULTS: RAC1 activity was markedly increased in the MB tissue compared to the normal cerebellum. RAC1 depletion sup …

Brain extracellular matrix implications in multiple neurological disorders revealed through a meta-analysis of transcriptional changes.

Neurological disorders comprise a wide range of illnesses that may affect the central and peripheral nervous systems. Despite their diverse … terns suggesting that GFAP (glial fibrillary acidic protein), a key intermediate filament in mature astrocytes and a well-known marker of reactive astrocytes, and IFITM3 (interferon-induced transmembrane protein 3), a crucial component of the first-line antiviral defense, were on average the most frequently reported genes among the studied disorders. Our stu …

Human Stem Cell-Derived Models of the Alzheimer's Disease Neuroimmune System.

Mounting evidence implicates dysregulation of the neuroimmune system in Alzheimer's disease (AD). Neuroimmune cells, namely microglia and astrocytes, have the potential to contribute to AD through mechanisms such as promoting neuroinflammation and propagating amyloid-β (Aβ) and tau aggregates. Human induced pluripotent stem cell (hiPSC)-derived models offer advantages for studying the AD neuroimmune system, such as recapitulating genetic variants associated with the disease and allowing for precise manipulation of human cells in vitro. Here, we provide an overview of modern techniques for gene…

Down-regulation of platelet-derived growth factor receptor β in pericytes increases blood-brain barrier permeability and significantly enhances α-synuclein in a Parkinson's Disease 3D cell model in vitro under hyperglycemic condition.

BACKGROUND: Parkinson's Disease (PD) often presents with a compromised blood-brain barrier (BBB), which hyperglycemia may exacerbate. Pericytes, a key cell for BBB integrity, are potential therapeutic targets for neurodegenerative disorders. Few studies have developed 3D PD cell models incorporating neurovascular units (NVU) through the co-culture of human endothelial, pericytes, astrocytes, and SH-SY5Y cells to evaluate BBB impairment and the role of pericytes under hyperglycemic condition. METHOD: A 3D PD like cell model was developed using 6-OHDA-affected SH-SY5Y cells, combined with endot…

Expression of CD44 and Its Spliced Variants: Innate and Inducible Roles in Nervous Tissue Cells and Their Environment.

CD44, a structurally diverse cell-surface glycoprotein, plays a multifaceted and indispensable role in neural tissue across both physiological and pathological conditions. It orchestrates complex cell-extracellular matrix interactions and intracellular signaling through its variant isoforms and post-translational modifications and is broadly expressed in neural stem/progenitor cells, microglia, astrocytes, and selected neuronal populations. The interactions of CD44 with ligands such as hyaluronan and osteopontin regulate critical cellular functions, including migration, differentiation, inflam…

The Therapeutic Potential of Butyrate and Lauric Acid in Modulating Glial and Neuronal Activity in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by amyloid-β plaque accumulation, tau tangles, and extensive neuroinflammation. Neuroinflammation, driven by glial cells like microglia and astrocytes, plays a critical role in AD progression. Initially, these cells provide protective functions, such as debris clearance and neurotrophic support. However, as AD progresses, chronic activation of these cells exacerbates inflammation, contributing to synaptic dysfunction, neuronal loss, and cognitive decline. Microglia release pro-inflammatory cytokines and reactive oxygen…

Magnolol Traverses the Blood-brain Barrier and Enhances Temozolomide-induced Intrinsic Apoptosis of Glioblastoma Cells via a p53 Redox Signaling Mechanism.

BACKGROUND/AIM: Temozolomide (TMZ) is the standard chemotherapeutic agent for glioblastoma multiforme (GBM), yet its efficacy is limited by severe side effects and high rates of drug resistance. This study investigated whether magnolol, a bioactive compound from Magnolia officinalis, enhances TMZ-induced apoptosis in glioblastoma cells and explored the underlying mechanisms. MATERIALS AND METHODS: The safety of magnolol was evaluated in normal human astrocytes and mouse cerebral endothelial cells (CECs). Its ability to traverse the CEC tight junction barrier was examined, followed by assessme…

SYSTEM XC- AS A MOLECULAR MECHANISM FOR EVOLUTIONARY NEW FORMS OF ADVANCED COGNITION.

Human cognitive abilities are deeply rooted in evolutionary building blocks that maximize computation while maintaining efficiency. These abilities are not without evolutionary signatures; conserved processes like vision have undergone continual phylogenetic adjustments to better serve ecological niches. Conversely, more sophisticated forms of cognition may have required evolutionary innovations to transform existing neuronal processing to expand computational abilities. One such innovation is system xc- (Sxc), a cystine-glutamate antiporter predominantly localized to astrocytes that emerged i…

Aβ Deposition in Extracellular Space Disrupts Glial-Neuron Communication and Triggers Alzheimer's Disease.

Disruptions in glial-neuron communication are linked to brain diseases; however, the exact mechanisms are not yet fully understood. This review highlights the critical role of glia-neuron interactions in sustaining normal brain functions. Under physiological conditions, astrocytes, microglia and oligodendrocytes, collaboratively regulate the homeostasis of brain structures and functions through diverse communication mechanisms. Conversely, under pathological conditions, disorders in glial-neuron communication can precipitate in neurodegenerative diseases, such as Alzheimer's Disease (AD). In A…

In vivo and in vitro susceptibility and inflammatory response of postnatal mouse cortical neurons and glial cells to zika virus infection.

Zika virus (ZIKV) poses a significant threat to neural tissue, causing substantial damage to unborn children exposed to the virus in utero, … the susceptibility to ZIKV infection, viral replication, immune response, and survival of neurons, astrocytes and microglial cells during postnatal developmental stages, using both in vivo and in vitro mice models. In vivo, a non-lethal but extensive infection of neurons and microglia was shown. The infection caused a robust but controlled immune response w …

Trisomy 21 Disrupts Thyroid Hormones Signaling During Human iPSC-Derived Neural Differentiation In Vitro.

Thyroid hormones (THs) are essential for brain development, and their dysregulation is associated with cognitive deficits and neurodevelopme … -and downstream target genes in hiPSCs, hiPSC-derived neural progenitor cells (NPCs), hiPSC-derived astrocytes, and hiPSC-derived neurons. DS-derived hiPSCs, hiPSC-derived NPCs, and hiPSC-derived neurons exhibited 2- to 7-fold increases in the gene expression of DIO2 and 3- to 8-fold reductions in DIO3, alongside 1- to 3-fold downregulation of THRA and THRB …

Consequences of Adhesion Molecule Close Homolog of L1 Deficiency for Neurons and Glial Cells in the Mouse Spinal Cord After Injury.

After spinal cord injury, pathological changes predominantly proceed caudal to the site of injury. To what extent these changes contribute t … ured mutant mice were lower than in wild-type littermates. Whereas injury did not affect numbers of astrocytes and oligodendrocytes in the gray matter, numbers of microglia/macrophages were increased. In the mutant white matter, numbers of oligodendrocytes were reduced, with no changes in numbers of astrocytes and microglia. A loss of motoneurons and interne …

Пересадка глиальных клеток человека в муринные мозги: систематический обзор эффективности и безопасности в нейродегенеративных расстройствах.

Справочная информация: Нейродегенеративные заболевания затрагивают миллионы людей во всем мире. С годами исследования мозга были сосредоточены главным образом на нейронах, но сейчас внимание перемещается на глиальные клетки, вспомогательные клетки мозга, которые играют жизненно важную роль в нейродегенеративных расстройствах. Таким образом, трансплантация глиальных клеток представляет собой новаторский подход к лечению различных нейродегенеративных расстройств, способных восстановить нейронную функцию. Мы провели оценку терапевтической эффективности трансплантации человеческих глиальных клеток

Совпадение в аннотации оригинала
Background: Neurodegenerative diseases impact millions of individuals globally. Over the years, brain research has predominantly focused on … and adverse outcomes were analyzed. Results: Study results highlight promising findings, including astrocytes improving motor function and slowing disease progression in neurodegenerative animal models through neurotrophic factor secretion and reduced inflammation. Similarly, microglia transplantation has demonstrated effectiveness in reducing α-synuclein t …

A Disintegrin And Metalloprotease 10 expression within the murine central nervous system.

A Disintegrin And Metalloprotease 10 (ADAM10), is able to control several important physiopathological processes through the shedding of a large number of protein substrates. Although ADAM10 plays a crucial role in the central nervous system (CNS) development and function, its protein distribution in the CNS has not been fully addressed. Here, we described the regional and cellular ADAM10 protein expression in C57BL/6 mice examined by immunofluorescence 1) throughout the adult mouse brain, cerebellum and spinal cord in vivo and 2) in different cell types as neurons, astrocytes, oligodendrocyte…

Linking Gba1 E326K mutation to microglia activation and mild age-dependent dopaminergic Neurodegeneration.

Mutations in the GBA1 gene have been identified as a prevalent genetic risk factor for Parkinson's disease (PD). GBA1 mutations impair enzym … . Furthermore, we observed increased levels of pro-inflammatory cytokines and formation of reactive astrocytes in primary microglia and astrocytes, respectively, cultured from Gba1 E326K KI mice following treatment with pathologic α-syn preformed fibrils (PFF). Additionally, the gut inoculation of α-syn PFF in Gba1 E326K KI mice significantly enhanced the ac …

Neurotoxic mechanisms of mycotoxins: Focus on aflatoxin B1 and T-2 toxin.

Aflatoxin B1 (AFB1) and T-2 toxin are commonly found in animal feed and stored grain, posing a serious threat to human and animal health. My … -brain barrier, toxins can directly affect glial cells, alter the activation state of microglia and astrocytes, thereby promoting brain inflammation, disrupting the blood-brain barrier, and influencing the synaptic transmission process. We discussed the diverse effects of various concentrations of toxins and different modes of exposure on neurotoxicity. In a …

Neuropathological findings in Down syndrome, Alzheimer's disease and control patients with and without SARS-COV-2: preliminary findings.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an incr … A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-rela …

Galectin-3 Plays a Role in Neuroinflammation in the Visual Pathway in Experimental Optic Neuritis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) featuring numerous neuropathologies, in … naïve and EAE mice during the chronic stage. Gal-3 was detected mainly in microglia/macrophages and astrocytes in the visual pathway in EAE mice. In addition, gal-3+/Iba-1+ cells, identified as phagocytic by immunostaining for cathepsin D, accumulated in demyelinating lesions in the visual pathway during the peak disease stage of EAE. Moreover, NLRP3 express …

Preclinical translational platform of neuroinflammatory disease biology relevant to neurodegenerative disease.

Neuroinflammation is a key driver of neurodegenerative disease, however the tools available to model this disease biology at the systems level are lacking. We describe a translational drug discovery platform based on organotypic culture of murine cortical brain slices that recapitulate disease-relevant neuroinflammatory biology. After an acute injury response, the brain slices assume a chronic neuroinflammatory state marked by transcriptomic profiles indicative of activation of microglia and astrocytes and loss of neuronal function. Microglia are necessary for manifestation of this neuroinflam…

An Association of Chitinase-3 Like-Protein-1 With Neuronal Deterioration in Multiple Sclerosis.

Elevated levels of Chitinase-3-like protein-1 (CHI3L1) in cerebrospinal fluid have previously been linked to inflammatory activity and disease progression in multiple sclerosis (MS) patients. This study aimed to investigate the presence of CHI3L1 in the brains of MS patients and in the cuprizone model in mice (CPZ), a model of toxic/metabolic demyelination and remyelination in different brain areas. In MS gray matter (GM), CHI3L1 was detected primarily in astrocytes and in a subset of pyramidal neurons. In neurons, CHI3L1 immunopositivity was associated with lipofuscin-like substance accumulat…