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M2 microglia-derived migrasome-enriched extracellular vesicles restore mitochondrial homeostasis to orchestrate neurovascular unit recovery after ischemic stroke.

Ischemic stroke is a major cause of disability with few treatment options available. Microglia-driven neuroinflammation contributes signific … cell models and MCAO mice. These migrasome-enriched EVs were efficiently internalized by microglia, astrocytes, neurons, and microvascular endothelial cells, promoting microglial M2 polarization, suppressing astrocytic aberrant activation, reducing neuronal apoptosis, and enhancing angiogenesis. Intracerebral administration of M2 microglia-derived migrasome- …

Connexin 50 mediates disease-relevant alpha-synuclein oligomer propagation and neuroinflammation in neurodegenerative disease.

Connexins, fundamental components of gap junctions and hemichannels, regulate intercellular communication and are emerging neurodegeneration regulators. Primary synucleinopathies and co-morbid synuclein pathologies feature pathological α-synuclein (α-Syn) aggregation, yet mechanisms driving pathogenic α-Syn propagation remain unclear. We identify that connexin 50 (Cx50) interacts with α-Syn aggregates in synucleinopathy-affected human brain tissue. Ex vivo dye uptake assays show markedly elevated hemichannel activity in synucleinopathy mouse brain tissue versus wild-type controls, suppressed b

Complement C3a induces synaptic elimination in the hippocampus and neurobehavioral deficits in later life of septic neonatal rats triggered by lipopolysaccharide.

Neonatal septic encephalopathy is a severe complication of sepsis, yet its underlying neuropathological mechanisms remain poorly understood. This study investigated the role of the complement component C3a in mediating synaptic elimination and neurobehavioral deficits in later life of a lipopolysaccharide (LPS)-induced neonatal sepsis model. We found that activated hippocampal astrocytes upregulated C3a expression, while its receptor, C3aR, was elevated in both microglia and neurons. Blocking the C3a/C3aR axis with a C3a receptor antagonist (C3aRA) attenuated cognitive impairments, synaptic lo…

Plasma GFAP and language-network tau mediate the effect of amyloid burden on semantic fluency: A mediation analysis.

INTRODUCTION: Amyloid burden may relate to semantic fluency through tau and astrocytic pathways, but their contributions remain unclear. METHODS: In this cross-sectional study, we analyzed 210 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants with amyloid positron emission tomography (PET), tau PET, plasma glial fibrillary acidic protein (GFAP), and animal fluency. Joint mediation models estimated indirect effects through language-network tau and GFAP, with subgroup analyses in amyloid beta (Aβ)-positive participants. RESULTS: In the full sample, both tau and GFAP significantly

2,6-diaminopurine enhances Aqp4 stop codon readthrough and AQP4 perivascular localization in the brain.

In the brain, the water channel Aquaporin 4 (AQP4) is largely restricted to astrocytes, enriched at perivascular astrocytic processes, and involved in fluid balance and neurological disease. The perivascular pool is functionally unique as it is depolarized in diseases, targeted by neuromyelitis optica autoantibodies, and implicated in the clearance of brain metabolites such as amyloid beta. The perivascular AQP4 was recently shown to be AQP4X, an extended isoform arising from readthrough, where approximately 20% of translating ribosomes continue through the Aqp4 stop codon. Because Aqp4 termin…

Neuroprotective Role of Synthetic Peptide DP1 in Reducing Inflammation-Associated Brain Damage and Cognitive Impairments.

Neuroinflammation serves as a central process in the development of various neurodegenerative diseases, often triggered by systemic inflammation. Within the realm of current scientific investigation, there is considerable interest in antimicrobial peptides (AMPs) due to their versatile attributes, extending beyond their traditional antimicrobial functions, encompassing significant anti-inflammatory properties. Among these, the novel peptide DP1 stands out as an example, exhibiting antimicrobial and anti-inflammatory properties. This study evaluates the anti-inflammatory potential of DP1 agains

iPSC-derived neurospheres: A cellular platform for Tau and Alzheimer's disease immunotherapy.

Alzheimer's disease is the most prevalent type of dementia, which is characterized by a progressive loss of memory and cognitive impairment. … on response to Tau aggregates, releasing cytokines and undergoing calcium homeostasis. iPSC-derived astrocytes demonstrated a reactive state and disruption in calcium homeostasis upon the exposure of the pathological proteins, contributing to neurodegeneration. Further, the mechanisms of Tau and Amyloid-β internalization in iPSC-derived cells provide insight …

Значение сыворотки фибрилкислого белка как биомаркера астроглиоза в различных неврологических заболеваниях.

Глиал фибриллярный протеин (GFAP) — хорошо известный биомаркер астроцитов и астроглиоза, патологический ответ, наблюдаемый в различных неврологических заболеваниях. Цель этого исследования заключалась в оценке диагностических характеристик сыворотки GFAP в болезни Альцгеймера (AD), множественных склерозов (MS) и транстиретинового амилоида (ATTR) полинеропратии. Мы провели ретроспективное исследование, в котором приняли участие 498 человек (337 здоровых и 161 пациент с амилоидозом AD, MS или ATTR). Уровни Serum GFAP измерялись с использованием платформы Lumipulse G1200, и был проведен статистич

Совпадение в аннотации оригинала
BACKGROUND: Glial Fibrillary Acidic Protein (GFAP) is a well-established biomarker of astrocytes and astrogliosis, a pathological response observed in various neurological diseases. This study aimed to evaluate the diagnostic performance of serum GFAP in Alzheimer's disease (AD), multiple sclerosis (MS), and transthyretin amyloidosis (ATTR) polyneuropathy. …

Nedl1 knockout impaired the learning and memory of mice.

BACKGROUND: Protein ubiquitination is a common post-translational modification involved in protein degradation and various life processes in … emory. Nedl1 knockout did not affect the number of neurons and oligodendrocytes in the hippocampus. Astrocytes proliferated in the hippocampus of Nedl1-/- mice. The amino acid metabolism of Nedl1+/+and Nedl1-/- mice is different, especially the increase in proline and tryptophan. CONCLUSION: This study showed that Nedl1 knockout impaired learning and memory …

Insulin Docking Within the Open Hemichannel of Connexin 43 May Reduce Risk of Amyotrophic Lateral Sclerosis.

BACKGROUND/AIM: Type 2 diabetes (T2D), characterized by hyperinsulinemia, protects motor neurons against amyotrophic lateral sclerosis (ALS). Type 1 diabetes and a total lack of insulin are associated with increased risk of ALS. Connexin 43 (Cx43), an astrocyte protein, operates as an open pore via which toxic substances from the astrocytes reach motor neurons. MATERIALS AND METHODS: In the current study, we performed molecular docking of insulin with monomeric Cx31, monomeric Cx43, and hexameric Cx31 to assess whether insulin might affect the pore. Hexameric Cx31 and hexameric Cx43 are trans…

Long-term microglia depletion impairs synapse elimination and auditory brainstem function.

Specialized sound localization circuit development requires synapse strengthening, refinement, and pruning. Many of these functions are carried out by microglia, immune cells that aid in regulating neurogenesis, synaptogenesis, apoptosis, and synaptic removal. We previously showed that postnatal treatment with BLZ945 (BLZ), an inhibitor of colony stimulating factor 1 receptor (CSF1R), eliminates microglia in the brainstem and disables calyceal pruning and maturation of astrocytes in the medial nucleus of the trapezoid body (MNTB). BLZ treatment results in elevated hearing thresholds and delaye…

A thermodynamic function of glycogen in brain and muscle.

Brain and muscle glycogen are generally thought to function as local glucose reserves, for use during transient mismatches between glucose s … row, spatially constrained astrocyte processes that ensheath neuronal synapses and in cells such as astrocytes and myocytes that release Pi from phosphocreatine during energy demand. The thermodynamic effect may also explain glycolytic super-compensation in brain when glycogen is not available, and aspects of exercise physiology in muscle glycogen phosphoryl …

In Situ Temporospatial Characterization of the Glial Response to Prion Infection.

Mammalian transmissible spongiform encephalopathies (TSEs) display marked activation of astrocytes and microglia that precedes neuronal loss. Investigation of clinical parallels between TSEs and other neurodegenerative protein misfolding diseases, such as Alzheimer's disease, has revealed similar patterns of neuroinflammatory responses to the accumulation of self-propagating amyloids. The contribution of glial activation to the progression of protein misfolding diseases is incompletely understood, with evidence for mediation of both protective and deleterious effects. Glial populations are het…

Oxygen-Induced Retinopathy from Recurrent Intermittent Hypoxia Is Not Dependent on Resolution with Room Air or Oxygen, in Neonatal Rats.

Preterm infants often experience intermittent hypoxia (IH) with resolution in room air (RA) or hyperoxia (Hx) between events. Hypoxia is a major inducer of vascular endothelial growth factor, which plays a key role in normal and aberrant retinal angiogenesis. This study tested the hypothesis that neonatal IH which resolved with RA is less injurious to the immature retina than IH resolved by Hx between events. Newborn rats were exposed to: (1) Hx (50% O₂) with brief hypoxia (12% O₂); (2) RA with 12% O₂; (3) Hx with RA; (4) Hx only; or (5) RA only, from P0 to P14. Pups were examined at P14 or pl

Chromatin Switches during Neural Cell Differentiation and Their Dysregulation by Prenatal Alcohol Exposure.

Prenatal alcohol exposure causes persistent neuropsychiatric deficits included under the term fetal alcohol spectrum disorders (FASD). Cellular identity emerges from a cascade of intrinsic and extrinsic (involving cell-cell interactions and signaling) processes that are partially initiated and maintained through changes in chromatin structure. Prenatal alcohol exposure influences neuronal and astrocyte development, permanently altering brain connectivity. Prenatal alcohol exposure also alters chromatin structure through histone and DNA modifications. However, the data linking alcohol-induced d

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an in vitro model of CNS tuberculosis.

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier … r Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Sh …

C1q, the classical complement pathway protein binds Hirano bodies in Pick's disease.

Haematoxylin/Eosin staining was performed to screen for Hirano bodies from the temporal lobe including the hippocampus in 10 Pick's disease … ent factor B. Hirano bodies also remained negative with the antiglial fibrillary acidic protein for astrocytes and HLA class II antibody CR3/43 for microglia. The results demonstrate that Hirano bodies have strong immunoreactivity to C1q; however, whether other complement components are associated with these inclusions remains to be further investigated.

Uteroplacental insufficiency alters rat hippocampal cellular phenotype in conjunction with ErbB receptor expression.

INTRODUCTION: Uteroplacental insufficiency (UPI) produces significant neurodevelopmental deficits affecting the hippocampus of intrauterine growth-restricted (IUGR) offspring. IUGR males have worse deficits as compared with IUGR females. The exact mechanisms underlying these deficits are unclear. Alterations in hippocampal cellular composition along with altered expression of neural stem cell (NSC) differentiation molecules may underlie these deficits. We hypothesized that IUGR hippocampi would be endowed with altered neuronal, astrocytic, and immature oligodendrocytic proportions at birth, wi

Temporal and cell-specific deletion establishes that neuronal Npc1 deficiency is sufficient to mediate neurodegeneration.

Niemann-Pick type C (NPC) disease is an autosomal recessive lysosomal storage disorder caused by mutations in the NPC1 or NPC2 genes. Loss o … s, CNS histopathology or synaptic function. We conclude that defects arising in neurons, but not in astrocytes, are the determining factor in the development of NPC neuropathology.

Amelioration of enteric neuropathology in a mouse model of Niemann-Pick C by Npc1 expression in enteric glia.

Niemann-Pick C (NPC) disease is an autosomal recessive, lethal, neurodegenerative disorder caused by mutations in NPC1. By using the glial fibrillary acidic protein (GFAP) promoter, we demonstrated previously that astrocyte-specific expression of Npc1 decreased neuronal storage of cholesterol in Npc1(-/-) mice; reduced numbers of axonal spheroids; and produced less degeneration of neurons, reactive astrocytes, and loss of myelin tracts in the central nervous system. GFAP-Npc1, Npc1(-/-) mice exhibited markedly enhanced survival, and death was not associated with the severe terminal weight loss…