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Norepinephrine-induced intracellular Ca2+ increase is coupled with astrocytic BK channel activation and capillary response.

Astrocytes are abundant glial cells organized in a meshwork in which each cell is in contact with both neuronal and vascular elements. They receive and respond to neuronal signals and modulate synaptic activity and diameter of blood vessels through changes in their intracellular Ca2+. Norepinephrine plays an important role in both of these astrocytic functions; however, it remains unclear whether norepinephrine-induced intracellular Ca2+ increase leads to further cellular adjustments in astrocyte activity. Here, we reveal a causal relationship between norepinephrine-induced intracellular Ca2+ …

Integrative Constraint-Based Modeling and Proteomics Uncover Astrocytic Metabolic Adaptations to the Post-TBI Microenvironment.

Traumatic brain injury (TBI) is a major neurological condition affecting millions of individuals each year. Mild TBI (mTBI) manifests differently, with some individuals experiencing persistent, debilitating symptoms while others recover more rapidly. Despite its classification as "mild," mTBI leads to both short- and long-term neurological effects, many of which occur due to functional changes in the brain. TBI-induced environmental changes within the brain play a critical role in shaping these functional outcomes. The importance of astrocytes in maintaining central nervous system (CNS) homeos…

Regulating astrocytic activity in the dorsal striatum mitigates L-dopa-induced dyskinesia in Parkinson's disease.

In Parkinson's disease (PD), long-term 3,4-dihydroxy-L-phenylalanine (L-dopa) therapy leads to the development of motor complications, including L-dopa-induced dyskinesia (LID). Increased numbers of reactive astrocytes in the brains of patients with PD are a key feature of this disease. Astrocytes are involved in the development of LID; however, whether the regulation of astrocytic activity influences LID development remains unclear. Therefore, this study aimed to determine the effect of the direct modulation of glial fibrillary acidic protein (GFAP)-expressing glia on LID development during L…

Piezo1 and Piezo2 Ion Channels in Neuronal and Astrocytic Responses to MEA Implants in the Rat Somatosensory Cortex.

Intracortical microelectrode arrays (MEAs) are tools for recording and stimulating neural activity, with potential applications in prostheti … y near the implant site. Furthermore, Piezo1-but not Piezo2-was strongly expressed in GFAP-positive astrocytes within 25 µm of the implant. Piezo2 expression appeared relatively uniform within each brain slice, both in and around the MEA implantation site across cortical layers. Our study builds on previous work by demonstrating a potential role of Piezo1 in …

Astrocytic heterogeneous nuclear ribonucleoprotein U is involved in scar formation after spinal cord injury.

Astrocytes have a beneficial role in tissue repair after central nervous system (CNS) injury. Although astrocyte proliferation is activated in response to injury, the intracellular mechanisms of astrocyte proliferation during acute phase of injury are not fully clarified. In this study, by functionally screening the highly expressed genes in the pathological state of spinal astrocytes, heterogeneous nuclear ribonucleoprotein U (Hnrnpu) is identified as a potential endogenous molecule that regulates astrocyte proliferation and the following scar formation. Inhibition of Hnrnpu in astrocytes imp…

Promoting astrocyte-neuron triiodothyronine shuttling attenuates brain damage in neonatal hypoxic-ischemic encephalopathy.

BACKGROUND: Neonatal Hypoxic-Ischemic Encephalopathy (HIE) is a critical lifelong disabling neonatal disease with insufficient effective the … ole-brain single-cell RNA sequencing was performed at P10, and proteomic profiling was conducted on astrocytes subjected to oxygen–glucose deprivation. We charted astrocyte diversity in situ using multiplex immunofluorescence. Thyroid hormones and signaling pathways were quantified by ELISA and Western blotting. Therapeutic efficacy was assessed by histopath …

Transcription factor RUNX2 participates in astrocyte-mediated neuropathic pain via transcriptional activation of Ccl2.

Neuroinflammation, which is characterized by glial cell activation and the release of inflammatory factors, is critical for the progression … c pain, RUNX2 expression was significantly increased in the spinal cord and was mainly localized to astrocytes. Knockdown of RUNX2 attenuated the astrocyte activation and the production of ROS and inflammatory factors induced by CCD surgery, thus relieving neuropathic pain. C-C motif chemokine ligand 2 (CCL2) has been reported to increase ROS generation, thu …

From glia limitans to glial scars: in vitro co-culture studies of the astrocyte and meningeal interaction.

The brain-meninges interface, comprising of astrocytes and meningeal cells seperated by a shared basement membrane, plays critical roles in the central nervous system. Recent work has shown the importance of signalling between the brain and the meninges in neurodevelopment, health, disease, and in stem cell migration. Despite this recent research, the brain-meninges interface is significantly understudied. This systematic review evaluates 27 studies which examine astrocyte-meningeal cell co-culture models. The papers were identified from a search of PubMed, Scopus, and Web of Science and scree…

Sleep-related changes in astrocytic biomarkers are modulated by APOE ε4 genotype in cognitively unimpaired adults.

Astrocytes are key regulators of sleep and neuroinflammatory responses. However, the relationship between objective sleep parameters and astrocytic fluid biomarkers in cognitively unimpaired individuals remains unclear. We examined how sleep architecture relates to astrocytic, neuroaxonal and Alzheimer's disease-related fluid biomarkers in cognitively unimpaired adults and whether age, sex and APOE ε4 moderate these associations. This cross-sectional study included 51 cognitively unimpaired participants from the Sant Pau Initiative on Neurodegeneration cohort. One-night in-lab polysomnography …

Proposed unified model of late-onset Alzheimer's disease: Chronic astrocytic and neuronal bioenergetic failure.

Late-onset Alzheimer's disease (LOAD) is framed here as progressive astrocyte-neuronal metabolic and neurovascular uncoupling initiated by astrocytic bioenergetic collapse. In genetically or environmentally predisposed brains, a self-reinforcing loop of lipid accumulation, inflammation, vascular impairment, glucose-handling defects, and mitochondrial dysfunction erodes astrocytic functional capacity. Subsequent cerebrovascular dysfunction and loss of blood-brain barrier (BBB) integrity perpetuate the neuroinflammatory response and drive amyloid-β deposition. Astrocytic failure then disrupts as

В Vivo Assessment of Cortical Astrocyte Network Dysфункция во время аутоиммунной демиелиции: корреляция с недугом.

Кортические повреждения и дисфункция являются патологической характеристикой множественного склероза (МС), который коррелирует с тяжестью физической и когнитивной инвалидности. Астроциты участвуют в патобиологии MS с помощью различных механизмов, и астроциклическое сигналирование кальция было указано как патогенный механизм кортикальной дисфункции в MS. В то же время в vivo доказательства дерегулирования механизмов, зависящих от астроцита кальция, в кортикальных MS по-прежнему ограничены. Здесь мы применили волокнистую фотометрию к продольному анализу спонтанной и сенсорной астроцитной активно

Совпадение в аннотации оригинала
Cortical damage and dysfunction is a pathological hallmark of multiple sclerosis (MS) that correlates with the severity of physical and cognitive disability. Astrocytes participate in MS pathobiology through a variety of mechanisms, and abnormal astrocytic calcium signaling has been pointed as a pathogenic mechanism of cortical dysfunction in MS. However, in…

Withaferin A protects against epilepsy by promoting LCN2-mediated astrocyte polarization to stopping neuronal ferroptosis.

BACKGROUND: Epilepsy is among the most frequent severe brain diseases, with few treatment options available. Neuronal ferroptosis is an impo … se depend. Furthermore, WFA treatment was proven to enhance to the transformation of post-epileptic astrocytes from neurotoxic-type A1 to A2 astrocytes in both in vivo and in vitro experiments by inhibiting the phosphoinositide 3-kinase /AKT signaling pathway. At last, transcriptomics analysis in combination with functional experimental validation, it was di …

Aerobic exercise improves astrocyte mitochondrial quality and transfer to neurons in a mouse model of Alzheimer's disease.

Mitochondrial dysfunction is a well-established hallmark of Alzheimer's disease (AD). Despite recent documentation of transcellular mitochondrial transfer, its role in the pathogenesis of AD remains unclear. In this study, we report an impairment of mitochondrial quality within the astrocytes and neurons of adult 5 × FAD mice. Following treatment with mitochondria isolated from aged astrocytes induced by exposure to amyloid protein or extended cultivation, cultured neurons exhibited an excessive generation of reactive oxygen species and underwent neurite atrophy. Notably, aerobic exercise enha…

Astrocytic proteins involved in regulation of the extracellular environment are increased in the Alzheimer's disease middle temporal gyrus.

Alzheimer's disease (AD) has complex pathophysiology involving numerous cell types and brain processes. Astrocyte involvement in AD is gaining increased attention, however a complete characterisation of astrocytic changes in the AD human brain is warranted. Astrocytes perform important homeostatic functions including regulation of the extracellular microenvironment, critical for the health of all brain cells. We have investigated changes to key astrocyte proteins involved in the regulation of CNS extracellular environment in the human AD middle temporal gyrus (MTG): aquaporin-4 (AQP-4), glutam…

Chrysophanol accelerates astrocytic mitochondria transfer to neurons and attenuates the cerebral ischemia-reperfusion injury in rats.

Astrocytes transfer extracellular functional mitochondria into neurons to rescue injured neurons after a stroke. However, there are no reports on drugs that interfere with intercellular mitochondrial transfer. Chrysophanol (CHR) was an effective drug for the treatment of cerebral ischemia-reperfusion injury (CIRI) and was selected as the test drug. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model and the middle cerebral artery occlusion animal model were established to investigate the effect of CHR on CIRI. The result showed that astrocytes could act as mitochondrial donors to a…

Empagliflozin Attenuates High-Glucose-Induced Astrocyte Activation and Inflammation via NF-κB Pathway.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors regulate blood glucose levels in patients with type 2 diabetes mellitus and may also exert anti-inflammatory and anti-atherosclerotic effects by promoting M2 macrophage polarization. Although SGLT2 is expressed in brain regions that influence glucose balance and cognitive function, its roles in the central nervous system are unclear. This study investigated the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic inflammation associated with metabolic diseases. Mice were subjected to a high-fat diet (HFD) for varying durations (

Olig2+/NG2+/BLBP+ astrocyte progenitors: a novel component of the neurovascular unit in the developing mouse hippocampus.

Astrocytes are key components of the neurovascular unit. While we have recently identified Olig2+ astrocyte progenitors (ASPs) in the developing mouse dentate gyrus (DG), their molecular signature remains incompletely characterized. Here we demonstrate that Olig2+ ASPs predominantly express brain lipid-binding protein (BLBP), while only a small population of them expresses gfap-GFP. These Olig2+/BLBP+ ASPs co-express the transcription factors Sox3, Sox9 and the proteoglycan NG2 but not Sox10, a marker for oligodendrocyte progenitors (OLPs). Olig2+ ASPs appear from embryonic day 18 (E18) onward…

Investigating Neuroplasticity Changes Reflected by BDNF Levels in Astrocyte-Derived Extracellular Vesicles in Patients with Depression.

PURPOSE: To investigate the neuroplasticity hypothesis of depression by measuring brain-derived neurotrophic factor (BDNF) levels in plasma astrocyte-derived extracellular vesicles (ADEVs) and to evaluate their potential as biomarkers for depression compared with plasma BDNF levels. PATIENTS AND METHODS: Thirty-five patients with major depressive disorder (MDD) and 35 matched healthy controls (HCs) were enrolled. Plasma ADEVs were isolated using a combination of ultracentrifugation and immunoaffinity capture. Isolated ADEVs were validated using transmission electron microscopy, nanoparticle t

Mechanisms and Therapeutic Prospects of Microglia-Astrocyte Interactions in Neuropathic Pain Following Spinal Cord Injury.

Neuropathic pain is a prevalent and debilitating condition experienced by the majority of individuals with spinal cord injury (SCI). The complex pathophysiology of neuropathic pain, involving continuous activation of microglia and astrocytes, reactive gliosis, and altered neuronal plasticity, poses significant challenges for effective treatment. This review focuses on the pivotal roles of microglia and astrocytes, the two major glial cell types in the central nervous system, in the development and maintenance of neuropathic pain after SCI. We highlight the extensive bidirectional interactions …

Ocular stress enhances contralateral transfer of lenadogene nolparvovec gene therapy through astrocyte networks.

Lenadogene nolparvovec (GS010) was developed to treat a point mutation in mitochondrial ND4 that causes Leber hereditary optic neuropathy. G … gap junction connexin 43 (Cx43), required for distant redistribution of metabolic resources between astrocytes during stress. After unilateral IOP elevation and GS010 injection, Cx43 knockdown eradicated ND4 RNA transcript detection in contralateral retinal tissues, while transcript was still detectable in optic nerves. Overall, our study indicates long-rang …