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BRAINCELL modelling platform for stochastic nanoscale organisation and dynamic extracellular signalling among neurons and glia.

Biophysical cell models have been central to understanding signal processing in brain cells and their networks, yet important limitations re … ic simulations of extracellular interactions between inhibitory and excitatory neurons, neurons and astrocytes, axons and myelin, microglia and ligand gradients. By integrating stochastic morphology with dynamic extracellular signalling, BRAINCELL produces task-specific predictions that often differ from conventional models. The platform is freely available …

Gangliosides in the 21st century: therapeutic prospects for the brain and spine.

Gangliosides are sialylated glycosphingolipids highly enriched in the central nervous system, where they regulate membrane signaling, metabolism, neurogenesis, and immune responses. This Review integrates recent advances across distinct experimental and clinical domains. First, recent studies demonstrate that the monosialoganglioside GM1 enhances astrocyte-neuron metabolic coupling via the astrocyte-neuron lactate shuttle, thereby supporting neuronal bioenergetics and resilience. Complementary mechanistic work shows that specific gangliosides regulate adult neurogenesis through developmentally

Карта мозга 4D Marmoset показывает МРТ и молекулярные сигнатуры начала множественных повреждений, подобных склерозу.

Подведение клеточной и молекулярной динамики множественных склерозовых (MS) повреждений после смерти тканей, собранных спустя десятилетия, является сложной задачей. С помощью направленного с помощью магнитного резонансного изображения (MRI) трафарктографического анализа RNA в экспериментальном аутоиммунном энцефалите (EAE) мы картировали динамику повреждений и моделировали молекулярные возмущения, имеющие отношение к MS. Было выявлено пять различных микроокружающих объектов, включая нейроглиальные реакции, разрушение и ремонт тканей, а также регулирование границ мозга. Перед демиелинцией МРТ в

Совпадение в аннотации оригинала
Inferring cellular and molecular dynamics of multiple sclerosis (MS) lesions from postmortem tissue collected decades after onset is challen … and oligodendrocyte precursors, later replaced by monocytes and lymphocytes. We highlight SERPINE1+ astrocytes as a signaling hub underlying lesion onset in both marmoset EAE and MS.

Acetate enables metabolic fitness and cognitive performance during sleep disruption.

Sleep is essential for overall health, and its disruption is linked to increased risks of metabolic, cognitive, and cardiovascular dysfunctions; however, the molecular mechanisms remain poorly understood. This study investigated how sleep disturbances contribute to metabolic imbalance and cognition impairment using a chronic sleep fragmentation (SF) mouse model. SF mice exhibited impaired cognition, glucose metabolism, and insulin sensitivity compared with controls. We identified increased acetate levels in hypothalamic astrocytes as a defensive response in SF mice. Through acetate infusion or…

Organization of Purkinje cell development by neuronal MEGF11 in cerebellar granule cells.

As cerebellar granule cells (GCs) coordinate the formation of regular cerebellar networks during postnatal development, molecules in GCs are … most of the cerebellar structures. Thus, apart from phagocytic functions of its related homologs in astrocytes, MEGF11 in GCs promotes proper PC development and cerebellar network formation by regulating immature synaptic transmission.

Asymmetric dysregulation of glutamate dynamics across the synaptic cleft in a mouse model of Alzheimer's disease.

Most research on glutamate spillover focuses on the deleterious consequences of postsynaptic glutamate receptor overactivation. However, two decades ago, it was noted that the glial coverage of hippocampal synapses is asymmetric: astrocytic coverage of postsynaptic sites exceeds coverage of presynaptic sites by a factor of four. The fundamental relevance of this glial asymmetry remains poorly understood. Here, we used the glutamate biosensor iGluSnFR, and restricted its expression to either CA3 or CA1 neurons to visualize glutamate dynamics at pre- and postsynaptic microenvironments, respectiv

Human striatal glia differentially contribute to AD- and PD-specific neurodegeneration.

The commonalities and differences in cell-type-specific pathways that lead to Alzheimer disease (AD) and Parkinson disease (PD) remain unknown. Here, we performed a single-nucleus transcriptome comparison of control, AD and PD striata. We describe three astrocyte subpopulations shared across different brain regions and evolutionarily conserved between humans and mice. We reveal common features between AD and PD astrocytes and regional differences that contribute toward amyloid pathology and neurodegeneration. In contrast, we found that transcriptomic changes in microglia are largely unique to …

AD-16 Protects Against Hypoxic-Ischemic Brain Injury by Inhibiting Neuroinflammation.

Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic (HI) insult in the neonatal brain. AD-16 is a novel anti-inflammatory compound, recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic mediators. In this study, we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation (OGD) in vitro and in mice with neonatal HI brain injury in vivo. We demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell injury. Single dose post-t…

Real-time imaging of glutamate clearance reveals normal striatal uptake in Huntington disease mouse models.

It has become well accepted that Huntington disease (HD) is associated with impaired glutamate uptake, resulting in a prolonged time-course … er (iGluSnFR) and electrophysiological recordings of synaptically activated transporter currents in astrocytes. These techniques reveal a disconnect between the results obtained in synaptosomes and those in situ. Exogenous glutamate uptake is impaired in synaptosomes, whereas real-time measures of glutamate clearance in the HD striatum are normal or even acc …

Propentofylline: glial modulation, neuroprotection, and alleviation of chronic pain.

Propentofylline is a unique methylxanthine with clear cyclic AMP, phosphodiesterase, and adenosine actions, including enhanced synaptic aden … rtite synaptic action of propentofylline that includes modulation of pre- and postsynaptic neurons, astrocytes, and microglia in the treatment of chronic pain syndromes, including, but not limited to, neuropathic pain.

An essential role for frizzled 5 in mammalian ocular development.

Microphthalmia, coloboma and persistent fetal vasculature within the vitreous cavity are among the most common human congenital ocular anoma … s of mesenchymal cells in the vitreous cavity, an excess of retinal astrocyte precursors and mature astrocytes, and persistence of the hyaloid vasculature in association with a large number of pigment cells. Fz5(-/-) mice also exhibit a late-onset progressive retinal degeneration by approximately 6 months of age, which might be related to the expression of F …

Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants.

Growth-promoting macroglia (aldynoglia) with growth properties and immunological markers similar to Schwann cells, are found in loci of the mammalian CNS where axon regeneration occurs throughout life, like the olfactory sytem, hypothalamus-hypophysis and the pineal gland. Contrary to Schwann cells, aldynoglia mingle freely with astrocytes and can migrate in brain and spinal cord. Transplantation of cultured and immunopurified olfactory ensheathing cells (OECs) in the spinal cord after multiple central rhizotomy, promoted sensory and central axon growth and partial functional restoration, judg…

Immunopathology of experimental African sleeping sickness: detection of cytokine mRNA in the brains of Trypanosoma brucei brucei-infected mice.

The immunopathology of Trypanosoma brucei brucei in the central nervous system was studied by using an experimental model of chronic meningoencephalitis in outbred CD-1 mice. Mice infected with T. b. brucei were treated with a subcurative dose of the trypanocidal compound diaminazine aceturate. These mice relapsed and were again drug treated. The brains were examined histologically and by immunocytochemistry to identify activated astrocytes. The polymerase chain reaction was used to detect cytokine RNA transcripts. The infected and treated animals developed severe chronic meningoencephalitis c…

PNS-CNS transitional zone of the first cranial nerve.

This study examined the ultrastructure of the region of transition where fascicles of olfactory axons leave the peripheral nervous system (PNS) to enter the central nervous system (CNS), the so-called PNS-CNS transitional zone. Adult rats were transcardially perfused with a solution of 1% glutaraldehyde and 1% paraformaldehyde, decapitated, and the heads decalcified over a period of several weeks in a solution of 1% glutaraldehyde in 0.1 M tetrasodium ethylenediamine tetraacetic acid; the latter solution was changed daily. It was found that astrocytes did not form the glia limitans at the nerv…

Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institut…

Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.

Behavioral and psychological symptoms of dementia (BPSD) affect the majority of patients with Alzheimer's disease (AD), substantially increasing caregiver burden and the likelihood of institutionalization. The clinical management of BPSD remains challenging because of its poorly understood pathogenesis, the limited efficacy of conventional interventions, and significant safety concerns associated with current treatments. These limitations underscore the urgent need to identify novel therapeutic targets and develop glia-centered treatment strategies. As essential components of the central nervo

Exploring Human Brain Metabolism via Genome-Scale Metabolic Modeling with Highlights on Multiple Sclerosis.

Cerebral dysfunctions give rise to a wide range of neurological diseases due to the structural and functional complexity of the human brain stemming from the interactive cellular metabolism of its specific cells, including neurons and glial cells. In parallel with advances in isolation and measurement technologies, genome-scale metabolic models (GEMs) have become a powerful tool in the studies of systems biology to provide critical insights into the understanding of sophisticated eukaryotic systems. In this study, brain cell-specific GEMs were reconstructed for neurons, astrocytes, microglia, …

The Role of Glial Cells in Synaptic Dysfunction: Insights into Alzheimer's Disease Mechanisms.

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that impacts a substantial number of individuals globally. Despite its … n this review, we aim to provide a summary of the role of various glial cells, including microglia, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells, in regulating synaptic dysfunction. This may offer a new perspective on investigating the underlying mechanisms of AD.

Glial Fibrillary Acidic Protein Astrocytopathy: Review of Pathogenesis, Imaging Features, and Radiographic Mimics.

Glial fibrillary acidic protein (GFAP) astrocytopathy is a recently described autoimmune inflammatory disorder of the CNS characterized by the presence of specific antibodies targeting the intracellular filament protein in mature astrocytes. The pathogenesis is heterogeneous and poorly understood, with around 20%-34% of cases occurring as a paraneoplastic syndrome, most frequently associated with ovarian teratomas. It presents clinically as acute or subacute encephalomyelitis, and the diagnosis relies on imaging and detection of GFAP-Immunoglobulin (GFAP-IgG) in the CSF. Characteristic imaging…