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Mashup Score: 1Syntaxin-1 is necessary for UNC5A-C/Netrin-1-dependent macropinocytosis and chemorepulsion - 6 month(s) ago
IntroductionBrain connectivity requires correct axonal guidance to drive axons to their appropriate targets. This process is orchestrated by guidance cues that exert attraction or repulsion to developing axons. However, the intricacies of the cellular machinery responsible for the correct response of growth cones are just being unveiled. Netrin-1 is a bifunctional molecule involved in axon pathfinding and cell migration that induces repulsion during postnatal cerebellar development. This process is mediated by UNC5 homolog receptors located on external granule layer (EGL) tracts.MethodsBiochemical, imaging and cell biology techniques, as well as syntaxin-1A/B (Stx1A/B) knock-out mice were used in primary cultures and brain explants.Results and discussionHere, we demonstrate that this response is characterized by enhanced membrane internalization through macropinocytosis, but not clathrin-mediated endocytosis. We show that UNC5A, UNC5B, and UNC5C receptors form a protein complex with th
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Mashup Score: 0
Peroxisome proliferator-activated receptor PPARγ coactivator-α (PGC-1α) is concentrated in inhibitory interneurons and plays a vital role in neuropsychiatric diseases. We previously reported some characteristic features of schizophrenia (SZ) in GABAergic neuron-specific Pgc-1alpha knockout (KO) mice (Dlx5/6-Cre: Pgc−1alphaf/f). However, there is a fundamental gap in the molecular mechanism by which the Pgc-1alpha gene is involved in the neurobehavioral abnormalities of SZ. The loss of critical period (CP) triggers–maturations of parvalbumin interneurons (PVIs) and brakes—and the formation of perineuronal nets (PNNs) implicates mistimed trajectories during adult brain development. In this study, using the Pgc-1alpha KO mouse line, we investigated the association of Pgc-1alpha gene deletion with SZ-like behavioral deficits, PVI maturation, PNN integrity and synaptic ultrastructure. These findings suggest that Pgc-1alpha gene deletion resulted in a failure of CP onset and closure, thereby
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Mashup Score: 4Age-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases - 6 month(s) ago
The chemokine fractalkine (FKN, CX3CL1), a member of the CX3C subfamily, contributes to neuron–glia interaction and the regulation of microglial cell activation. Fractalkine is expressed by neurons as a membrane-bound protein (mCX3CL1) that can be cleaved by extracellular proteases generating several sCX3CL1 forms. sCX3CL1, containing the chemokine domain, and mCX3CL1 have high affinity by their unique receptor (CX3CR1) which, physiologically, is only found in microglia, a resident immune cell of the CNS. The activation of CX3CR1contributes to survival and maturation of the neural network during development, glutamatergic synaptic transmission, synaptic plasticity, cognition, neuropathic pain, and inflammatory regulation in the adult brain. Indeed, the various CX3CL1 forms appear in some cases to serve an anti-inflammatory role of microglia, whereas in others, they have a pro-inflammatory role, aggravating neurological disorders. In the last decade, evidence points to the fact that sCX
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Mashup Score: 11Human BBB-on-a-chip reveals barrier disruption, endothelial inflammation, and T cell migration under neuroinflammatory conditions - 6 month(s) ago
The blood-brain barrier (BBB) is a highly selective barrier that ensures a homeostatic environment for the central nervous system (CNS). BBB dysfunction, inflammation, and immune cell infiltration are hallmarks of many CNS disorders, including multiple sclerosis and stroke. Physiologically relevant human in vitro models of the BBB are essential to improve our understanding of its function in health and disease, identify novel drug targets, and assess potential new therapies. We present a BBB-on-a-chip model comprising human brain microvascular endothelial cells (HBMECs) cultured in a microfluidic platform that allows parallel culture of 40 chips. In each chip, a perfused HBMEC vessel was grown against an extracellular matrix gel in a membrane-free manner. BBBs-on-chips were exposed to varying concentrations of pro-inflammatory cytokines tumor necrosis factor alpha (TNFα) and interleukin-1 beta (IL-1β) to mimic inflammation. The effect of the inflammatory conditions was studied by asses
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Mashup Score: 3
Tanshinone IIA serves as a coenzyme for certain biochemical reactions, exhibiting various pharmacological effects in the treatment of neurological diseases including spinal cord injury (SCI), however, its working mechanism in the treatment of SCI is not clear. Based on previous research, we believe that tanshinone IIA promotes the survival and repair of nerves after spinal cord injury through its pharmacological effects such as anti-inflammatory, antioxidant, and prevention of cellular apoptosis in the spinal cord.
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Mashup Score: 2Scratching increases epidermal neuronal branching and alters psychophysical testing responses in atopic dermatitis and brachioradial pruritus - 6 month(s) ago
BackgroundChronic scratching imposes a major stress on the skin and can lead to itch intensity worsening, and consequently, patients may enter an itch–scratch cycle. This repetitive mechanical stress can result in lichenification, worsening of epidermal barrier function, and enhanced cutaneous inflammation. Furthermore, a reduction of intraepidermal nerve fibers was previously described in lichenification.AimThe aim of this study was to investigate the influence of chronic scratching on the epidermal neuroanatomy and on sensory changes, in particular the prevalence of hyperknesis and alloknesis in patients after mechanical, chemical, and electrical stimuli.MethodsAnalyses were performed on pruritic lichenified (chronically scratched), pruritic non-lichenified (not chronically scratched), and non-pruritic non-lesional (unaffected) skin areas of patients with inflammatory pruritus, i.e., atopic dermatitis (n = 35), and neuropathic pruritus, i.e., brachioradial pruritus (n = 34) vs. healt
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Mashup Score: 0
IntroductionGerminal Matrix-Intraventricular Haemorrhage (GM-IVH) is one of the most common neurological complications in preterm infants, which can lead to accumulation of cerebrospinal fluid (CSF) and is a major cause of severe neurodevelopmental impairment in preterm infants. However, the pathophysiological mechanisms triggered by GM-IVH are poorly understood. Analyzing the CSF that accumulates following IVH may allow the molecular signaling and intracellular communication that contributes to pathogenesis to be elucidated. Growing evidence suggests that miRs, due to their key role in gene expression, have a significant utility as new therapeutics and biomarkers.MethodsThe levels of 2,083 microRNAs (miRs) in 15 CSF samples from 10 infants with IVH were measured using miRNA whole transcriptome sequencing. Gene ontology (GO) and miR family analysis were used to uncover dysregulated signalling which were then validated in vitro in human foetal neural progenitor cells treated with IVH-CS
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Mashup Score: 2A juvenile mouse model of anti-N-methyl-D-aspartate receptor encephalitis by active immunization - 7 month(s) ago
IntroductionAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a common autoimmune encephalitis, and it is associated with psychosis, dyskinesia, and seizures. Anti-NMDAR encephalitis (NMDARE) in juveniles and adults presents different clinical charactreistics. However, the pathogenesis of juvenile anti-NMDAR encephalitis remains unclear, partly because of a lack of suitable animal models.MethodsWe developed a model of juvenile anti-NMDAR encephalitis using active immunization with an amino terminal domain peptide from the GluN1 subunit (GluN1356 − 385) against NMDARs in 3-week-old female C57BL/6J mice.ResultsImmunofluorescence staining suggested that autoantibody levels in the hippocampus increased, and HEK-293T cells staining identified the target of the autoantibodies as GluN1, suggesting that GluN1-specific immunoglobulin G was successfully induced. Behavior assessment showed that the mice suffered significant cognition impairment and sociability reduction, which is similar
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Mashup Score: 2
Neurodegenerative diseases (NDDs) pose an increasingly prevalent threat to the well-being and survival of elderly individuals worldwide. NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and so on. They are characterized by progressive loss or dysfunction of neurons in the central or peripheral nervous system and share several cellular and molecular mechanisms, including protein aggregation, mitochondrial dysfunction, gene mutations, and chronic neuroinflammation. Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase that is believed to play a pivotal role in the pathogenesis of NDDs. Here we summarize the structure and physiological functions of GSK3β and explore its involvement in NDDs. We also discussed its potential as a therapeutic target.
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Mashup Score: 0Neurodegeneration and its potential markers in the diagnosing of secondary progressive multiple sclerosis. A review - 7 month(s) ago
Approximately 70% of relapsing-remitting multiple sclerosis (RRMS) patients will develop secondary progressive multiple sclerosis (SPMS) within 10–15 years. This progression is characterized by a gradual decline in neurological functionality and increasing limitations of daily activities. Growing evidence suggests that both inflammation and neurodegeneration are associated with various pathological processes throughout the development of MS; therefore, to delay disease progression, it is critical to initiate disease-modifying therapy as soon as it is diagnosed. Currently, a diagnosis of SPMS requires a retrospective assessment of physical disability exacerbation, usually over the previous 6–12 months, which results in a delay of up to 3 years. Hence, there is a need to identify reliable and objective biomarkers for predicting and defining SPMS conversion. This review presents current knowledge of such biomarkers in the context of neurodegeneration associated with MS, and SPMS conversio
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New Research: Syntaxin-1 is necessary for UNC5A-C/Netrin-1-dependent macropinocytosis and chemorepulsion: Introduction Brain connectivity requires correct axonal guidance to drive axons to their appropriate targets. This process… https://t.co/kfkDLrwmF4 #Molecular #Neuroscience