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Decoding dengue's neurological assault: insights from single-cell CNS analysis in an immunocompromised mouse model.

BACKGROUND: Dengue encephalitis, a severe neurological complication of dengue virus infection, is increasingly recognized for its rising incidence and significant public health burden. Despite its growing prevalence, the underlying mechanisms and effective therapeutic strategies remain poorly understood. METHODS: Cellular atlas of dengue encephalitis was determined by single-nucleus RNA sequencing. Viral load of dengue virus and the level of cytokines expression was detected by RT-qPCR. The target cells of dengue virus were verified by immunofluorescence. The cytotoxic effect of CD8+ T cell w

Immunogenic self-DNA drives neuropsychiatric systemic lupus erythematosus in conventional genetic background mice.

Neuropsychiatric systemic lupus erythematosus (NPSLE) represents a significant and growing challenge in both clinical practice and research, … of anxiety-like and depression-like behaviors. In parallel, electrophysiological analysis revealed synaptic transmission deficits and reduced neuronal excitability beginning at week 8, further deteriorating by week 12. Of note, blood-brain barrier (BBB) disruption was observed at 4-8 weeks post immunization, which was evidenced by IgG leakage and FITC-dextran extravas …

Стимулятор Интерферон Генз (STING)-Type I Interferon Signaling: Преодоление иммунитета и боли.

Интерфероны (IFN) являются цитокинами с различными функциями, обладающими антивирусными, антипролиферативными и иммуномодулятивными эффектами. IFN-α и IFN-β, ключевые члены семейства интерферонов типа I (IFN-I), широко используются для лечения таких заболеваний, как гепатит и множественный склероз. В нервной системе микроглии, астроциты и нейроны выражают рецепторы IFN-I. Помимо своих классических функций транскрипции, IFN-I могут подавлять нейронную активность и синаптическую трансмиссию с помощью негеномных механизмов, создавая мощные анальгетические эффекты. Однако IFN-I активно участвует в

Совпадение в аннотации оригинала
Interferons (IFNs) are cytokines with diverse functions, possessing antiviral, antiproliferative, and immunomodulatory effects. IFN-α and IF … receptors. Beyond their classical transcriptional roles, IFN-Is can suppress neuronal activity and synaptic transmission through nongenomic mechanisms, producing potent analgesic effects. However, IFN-Is are active in signaling pathways such as phosphoinositide 3-kinase (PI3K), mitogen-activated protein kinase (MAPK), and the MAPK-interacting serine/threonine-protein …

Novel insight into atogepant mechanisms of action in migraine prevention.

Recently, we showed that while atogepant-a small-molecule calcitonin gene-related peptide (CGRP) receptor antagonist-does not fully prevent … ersus sensitization can explain how reduction in CGRP-mediated slow but not glutamate-mediated fast synaptic transmission between central branches of meningeal nociceptors and nociceptive neurons in the spinal trigeminal nucleus can prevent their sensitization but not activation.

Assessing the Effect of Fatigue on Swallowing Function in Adults with Acute Stroke. A Pilot Study.

OBJECTIVE: To determine if fatigue systematically effects the timing of swallowing events and to discuss underlying causes of fatigue other … ggest that the inconsistencies may stem from a delayed excitatory response of neurons or a delay in synaptic transmission within the nucleus tractus solitarius, potentially associated with stroke. This delay likely contributes to the prolongation of both pharyngeal transit and pharyngeal delay times. Thus, a model focused solely on peripheral neuromuscular fatigue does …

Astragaloside IV mediates radiation-induced neuronal damage through activation of BDNF-TrkB signaling.

BACKGROUND: Electromagnetic radiation is relevant to human life, and radiation can trigger neurodegenerative diseases by altering the function of the central nervous system through oxidative stress, mitochondrial dysfunction, and protein degradation. Astragaloside IV (AS-IV) is anti-oxidative, anti-apoptotic, activates the BDNF-TrkB pathway and enhances synaptic plasticity in radiated mice, which can exert its neuroprotection. However, the exact molecular mechanisms are still unclear. PURPOSE: This study investigated whether AS-IV could play a neuroprotective role by regulating BDNF-TrkB path

Opposite effects of acute and chronic IGF1 on rat dorsal root ganglion neuron excitability.

Insulin-like growth factor-1 (IGF-1) is a polypeptide hormone with a ubiquitous distribution in numerous tissues and with various functions in both neuronal and non-neuronal cells. IGF-1 provides trophic support for many neurons of both the central and peripheral nervous systems. In the central nervous system (CNS), IGF-1R signaling regulates brain development, increases neuronal firing and modulates synaptic transmission. IGF-1 and IGF-IR are not only expressed in CNS neurons but also in sensory dorsal root ganglion (DRG) nociceptive neurons that convey pain signals. DRG nociceptive neurons e…

β-Glucan alleviates goal-directed behavioral deficits in mice infected with Toxoplasma gondii.

BACKGROUND: Toxoplasma gondii (T. gondii) is a neuroinvasive parasite causing neuroinflammation, which in turn is associated with a higher risk for several psycho-behavioral disorders. There is an urgent need to identify drugs capable of improving cognitive deficits induced by T. gondii infection. β-Glucan, an active ingredient in mushrooms, could significantly enhance immunity. However, the effects of β-glucan against neuroinflammation and cognitive decline induced by T. gondii infection remain unknown. The present study aimed to investigate the neuroprotective effect of β-glucan on goal-dire

The profiles and clinical significance of extraocular muscle-expressed lncRNAs and mRNAs in oculomotor nerve palsy.

INTRODUCTION: Oculomotor nerve palsy (ONP) arises from primary abnormalities in the central neural pathways that control the extraocular mus … y expressed mRNAs were identified. The up-regulated mRNAs were significantly related to cholinergic synaptic transmission (such as CHRM3 and CHRND) and the components and metabolism of extracellular matrix (such as CHI3L1 and COL19A1), while the down-regulated mRNAs were significantly correlated with the composition (such as MYH7 and MYL3) and contraction force (such a …

Pilot study evaluating everolimus molecular mechanisms in tuberous sclerosis complex and focal cortical dysplasia.

BACKGROUND: Tuberous sclerosis complex (TSC) and some focal cortical dysplasias (FCDs) are associated with dysfunctional mTOR signaling, res … tified 5 significant modules. Higher phospho-S6 correlated negatively with cellular respiration and synaptic transmission and positively with organophosphate metabolic process, nuclear mRNA catabolic process, and neuron ensheathment. Brain metabolomics identified 14 increased features in Active participants, including N-acetylaspartylglutamic acid. Plasma proteomics an …

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression.

Major depressive disorder (MDD) is a prevalent, chronic, and relapse-prone psychiatric disease. However, the intermediate molecules resultin … EGs in the DG, such as cell adhesion, proteolysis, ion transport, transmembrane transport, chemical synaptic transmission, immune system processes, response to lipopolysaccharide, and nervous system development, may reveal the molecular mechanism of MDD. However, the DEGs in the ACC involved metabolic processes, proteolysis, visual learning, DNA methylation, innate imm …

Vinpocetine amended prenatal valproic acid induced features of ASD possibly by altering markers of neuronal function, inflammation, and oxidative stress.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex etiology and phenotypes. Phosphodiesterase-1 (PDE1) inhibitors … nt biochemical markers of neuronal function (DCX-neurogenesis, BDNF-neuronal survival, synapsin-IIa-synaptic transmission, pCREB-neuronal transcription factor), inflammation (interleukin [IL]-6, IL-10, and TNF-α) and oxidative stress (thiobarbituric acid reactive substance [TBARS] and glutathione (GSH) were studied in important brain areas (frontal cortex, cerebral cor …

Neuroprotective effects of allopurinol on spinal cord injury in rats: a biochemical and immunohistochemical study.

BACKGROUND: Lesion in spinal cord causes a cascade of events such as the apoptosis of neurons and eventually, neurological dysfunction. Neur … on. Glial fibrillary acidic protein (GFAP) takes part in astrocyte and neuronal interconnection and synaptic transmission. MATERIALS AND METHODS: Male Sprague Dawley rats (n = 30) were divided as control, trauma, and trauma + allopurinol (i.p., 50 mg/kg of body weight) groups. Animals were applied a surgical procedure causing spinal cord injury and treated for 7 days …

Gene expression analysis of the cerebellar cortex in essential tremor.

Essential tremor (ET) is one of the most common neurological diseases, with a central feature of an 8-12 Hz kinetic tremor. While previous p … crotubule motor activity, 3) endoplasmic reticulum (ER) to Golgi transport and 4) calcium signaling/synaptic transmission. The results of our transcriptomic analysis suggest there is a range of different processes involved among ET cases, and draws attention to a particular set of genes and regulatory pathways that provide an initial platform to further explore the und …

Functional Status of Neuronal Calcium Sensor-1 Is Modulated by Zinc Binding.

Neuronal calcium sensor-1 (NCS-1) protein is abundantly expressed in the central nervous system and retinal neurons, where it regulates many vital processes such as synaptic transmission. It coordinates three calcium ions by EF-hands 2-4, thereby transducing Ca2+ signals to a wide range of protein targets, including G protein-coupled receptors and their kinases. Here, we demonstrate that NCS-1 also has Zn2+-binding sites, which affect its structural and functional properties upon filling. Fluorescence and circular dichroism experiments reveal the impact of Zn2+ binding on NCS-1 secondary and t…

Recurrent epileptiform discharges in the medial entorhinal cortex of kainate-treated rats are differentially sensitive to antiseizure drugs.

OBJECTIVE: Approximately 30% of patients with epilepsy are refractory to existing antiseizure drugs (ASDs). Given that the properties of the … oncentrations near their average therapeutic plasma concentrations. γ-aminobutyric acid (GABA)ergic synaptic transmission-modulating ASDs (clobazam, midazolam, phenobarbital, stiripentol, tiagabine, and vigabatrin) attenuated REDs only at higher concentrations and, in some cases, prolonged RED durations. ASDs with other/mixed mechanisms of action (bumetanide, ethosuxim …

Recent advances in acetylcholinesterase Inhibitors and Reactivators: an update on the patent literature (2012-2015).

Acetylcholinesterase (AChE) is the major enzyme that hydrolyzes acetylcholine, a key neurotransmitter for synaptic transmission, into acetic acid and choline. Mild inhibition of AChE has been shown to have therapeutic relevance in Alzheimer's disease (AD), myasthenia gravis, and glaucoma among others. In contrast, strong inhibition of AChE can lead to cholinergic poisoning. To combat this, AChE reactivators have to be developed to remove the offending AChE inhibitor, restoring acetylcholine levels to normal. Areas covered: This article covers recent advances in the development of acetylcholine…

BAF53b, a Neuron-Specific Nucleosome Remodeling Factor, Is Induced after Learning and Facilitates Long-Term Memory Consolidation.

Although epigenetic mechanisms of gene expression regulation have recently been implicated in memory consolidation and persistence, the role … 53b before training disrupted long-term memory formation with no effect on short-term memory, basal synaptic transmission, and spine structures. We observed in our qPCR analysis that BAF53b was induced in the lateral amygdala neurons at the late consolidation phase after fear conditioning. Moreover, transient BAF53b overexpression led to persistently enhanced memory fo …

Methamphetamine acutely inhibits voltage-gated calcium channels but chronically up-regulates L-type channels.

In neurons, calcium (Ca(2+) ) channels regulate a wide variety of functions ranging from synaptic transmission to gene expression. They also induce neuroplastic changes that alter gene expression following psychostimulant administration. Ca(2+) channel blockers have been considered as potential therapeutic agents for the treatment of methamphetamine (METH) dependence because of their ability to reduce drug craving among METH users. Here, we studied the effects of METH exposure on voltage-gated Ca(2+) channels using SH-SY5Y cells as a model of dopaminergic neurons. We found that METH has differ…

Protection by glia-conditioned medium in a cell model of Huntington disease.

The physiological role of huntingtin and the pathogenic mechanisms that produce the disease are unknown. Mutant huntingtin changes its normal localization and produces cytoplasmic and intranuclear inclusions, changes gene transcription, alters synaptic transmission, impairs mitochondrial activity and activates caspases and other pro-apoptotic molecules, promotes excitotoxicity, energy deficits, synthesis and release reduction of neurotrophic factors and oxidative stress. Previous studies confirm that the mutant huntingtin difficult neurotrophic function of astrocytes leading to neuronal dysfun…