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Somatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation.

Somatostatin-expressing (SST) interneurons modulate hemodynamic responses both directly and indirectly, but their precise role remains unclear. Here, we investigated the influence of SST interneurons on hemodynamic control in response to optogenetic stimulation of SST neurons and somatosensory stimulation in both awake and anesthetized mice. Prolonged optogenetic stimulation of SST neurons induces fast vasodilation through nitric oxide synthase-expressing neurons that co-express SST, and slow vasodilation mediated by astrocytes. Similar neurovascular coupling mechanisms are observed during pro…

Targeting the cholinergic-astrocyte axis: A novel strategy for brain metastasis prevention in lung adenocarcinoma.

Brain metastasis (BM) represents a highly detrimental complication of lung adenocarcinoma (LUAD), persisting even following curative resection of primary tumors, with limited effective preventive measures. This study explores the role of cholinergic metabolism, a pathway crucial for both LUAD progression and brain function, in the pathogenesis of BM. Through comprehensive analysis of RNA-sequencing data from 875 LUAD cases and validation using tissue microarrays from 280 patients, we identified cholinergic metabolic activation as a defining characteristic of tumors prone to BM, which is signif

Lipocalin-2 regulates astrocyte-oligodendrocyte interaction to drive post-stroke secondary demyelination.

Secondary demyelination worsens outcomes after cerebral infarction, but astrocyte-oligodendrocyte interactions in this process remain unclear. Using distal middle cerebral artery occlusion (dMCAO) in mice, we show that lipocalin-2 (LCN2), partially diffusing from the infarct-adjacent corpus callosum, is transcriptionally and translationally upregulated in reactive astrocytes of the contralateral corpus callosum by 7 days post-injury. At upstream levels, PERK-orchestrated endoplasmic reticulum stress drives contralateral astrocytic activation and autonomous LCN2 synthesis. Subsequent LCN2 uptak…

NSUN2 enhances the stability of PTPRD mRNA via m5C methylation to aggravate astrocyte activation.

This study attempts to investigate the functional role of NOP2/Sun RNA methyltransferase 2 (NSUN2) in astrocyte activation and inflammatory … ors and m5C levels. Bioinformatics analysis identified m5C-related proteins associated with TBI and astrocytes. RT-qPCR detected NSUN2 expression, and immunofluorescence examined NSUN2-glial fibrillary acidic protein (GFAP) colocalization. In vitro experiments included m5C level detection, RNA immunoprecipitation, and RNA stability assays. Flow cytometry ana …

Astrocytic connexin43 phosphorylation contributes to seizure susceptibility after mild traumatic brain injury.

Astrocytes play a crucial role in maintaining brain homeostasis through functional gap junctions (GJs) primarily formed by connexin43 (Cx43) in the cortical gray matter. These GJs facilitate electrical and metabolic coupling between astrocytes, allowing the passage of ions, glucose, and metabolites. Dysregulation of Cx43 has been implicated in various pathologies, including traumatic brain injury (TBI) and acquired epilepsy. After mild TBI/concussion, we previously identified a subset of atypical astrocytes, which are correlated with the development of spontaneous seizures. These astrocytes ex…

Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice.

BACKGROUND: Reports indicate that depression is a common mental health issue following traumatic brain injury (TBI). Our prior research suggests that Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-related neuroinflammation, modulated by glial cells such as astrocytes, is likely to play a crucial role in the progression of anxiety and cognitive dysfunction. However, there is limited understanding of the potential of astrocytic NLRP3 in treating depression under mild TBI condition. This study aimed to determine whether astrocytic NLRP3 knockout (KO) could mitigate depr…

Neural tube defects induce abnormal astrocyte development by activation and epigenetic permissiveness of STAT3.

The open neural tube defect, myelomeningocele (MMC), is a debilitating congenital defect of the central nervous system, characterized by impaired spinal cord development. The pathological development of MMC spinal cord involves enhanced astrogenesis. However, the mechanisms underlying the abnormal generation of astrocytes in MMC spinal cord are poorly understood. Using a fetal rat model of this defect, we discovered that neural progenitor cells (NPCs) in the developing spinal cord undergo the accelerated acquisition of astrocytic competency and the abnormal induction of GFAP expression, result…

Astrocyte-microglia crosstalk in the hippocampus mediates cognitive impairments induced by chronic intermittent hypoxia.

Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a common systemic disease with a high-risk factor for … liorated these CIH-induced impairments. Furthermore, CIH enhanced the interaction between activated astrocytes and microglia, accompanied by upregulation of complement C3 in astrocytes and C3aR in microglia. Notably, blocking C3aR with SB290157 attenuated microglial overactivation, reduced aberrant synaptic engulfment, and improved cognitive performance in C …

Astrocyte lactoferrin deficiency affects the construction and function of spinal neurons by regulating cholesterol metabolism.

Astrocytes play pivotal roles in central nervous system (CNS) homeostasis, with emerging evidence implicating astrocyte-derived lactoferrin (Lf) in neurodevelopmental and neurodegenerative processes. This study investigates Lf's functional significance in spinal cord integrity using astrocyte-specific Lf knockout (cKO) mice. Behavioral analyses of 1-month-old male cKO mice revealed impaired motor coordination (increased balance beam scores and prolonged pole-climbing latency) and delayed nociceptive responses (increased thermal withdrawal latency). Morphological assessments demonstrated neuron…

Astrocyte heterogeneity and gliosis in Huntington's disease: Histopathological insights into striatal and white matter pathology.

Huntington's disease (HD) is a devastating, autosomal dominant neurodegenerative disorder characterized by progressive motor dysfunction, co … ting from the secondary cortex and passing through the striatum. While the functional role of these astrocytes remains unclear, they express Glial Fibrillary Acidic Protein (GFAP), a marker typically associated with both fibrous and reactive astrocytes. The discovery of this white matter-associated astrocyte subtype, along with other astrocytic subtypes diff …

Identification of a reactive astrocyte subpopulation during HIV-associated pain pathogenesis in mouse models.

Pain is a common complication in individuals with HIV, yet the underlying pathogenic mechanisms remain poorly understood. Reactive astrocytes are selectively activated in the spinal dorsal horn of HIV patients experiencing pathological pain, implicating their potential role in pain pathogenesis. However, the specific pathogenic subtype of these reactive astrocytes has not been defined. Here, we identify a distinct subpopulation of pain-associated reactive astrocytes in the lumbar spinal cord of HIV-1 gp120 transgenic mice using single-nucleus RNA sequencing. This astrocyte subpopulation displa…

Убиквитационное регулирование гликолитического фермента MCT4 в поощрении астроцитной реактивности во время нейроинфламмации.

Одним из гистопатологических признаков нервно-воспалительных заболеваний, таких, как множественный склероз (MS), является появление астроцитной реактивности. Накопление данных свидетельствует о том, что чрезмерный гликолиз может привести к астроцитной реактивности и способствовать нейроэнфламативным реакциям. Однако сложные механизмы, лежащие в основе метаболического перепрограммирования астроцитов в направлении гликолиза, остаются в значительной степени неизвестными. Здесь мы провели эксперименты in vitro с использованием первичных астроцитов и в vivo в экспериментальной аутоиммунной энцефало

Совпадение в аннотации оригинала
One of the histopathological hallmarks of neuroinflammatory diseases such as multiple sclerosis (MS) is the emergence of astrocyte reactivit … ng towards glycolysis remain largely unknown. Here, we conducted in vitro experiments using primary astrocytes and in vivo studies in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS). We observed increased astrocytic expression of MCT4, a key glycolytic regulator, in EAE mice. MCT4 enhanced astrocyte reactivity throug …

Astrocytic Neuroligin-3 influences gene expression and social behavior, but is dispensable for synapse number.

Neuroligin-3 (Nlgn3) is an autism-associated cell-adhesion molecule that interacts with neurexins and is robustly expressed in both neurons and astrocytes. Neuronal Nlgn3 is an essential regulator of synaptic transmission but the function of astrocytic Nlgn3 is largely unknown. Given the high penetrance of Nlgn3 mutations in autism and the emerging role of astrocytes in neuropsychiatric disorders, we here asked whether astrocytic Nlgn3 might shape neural circuit properties in the cerebellum similar to neuronal Nlgn3. Imaging of tagged Nlgn3 protein produced by CRISPR/Cas9-mediated genome editi…

Mechanism of S100A9-mediated astrocyte activation via TLR4/NF-κB in Parkinson's disease.

Astrocyte-mediated neuroinflammation plays a key role in Parkinson's disease (PD) progression. The proinflammatory protein S100A9 is linked … (TH+) in the substantia nigra (SN) in PD mice. Interestingly, S100A9 was predominantly expressed in astrocytes (GFAP+S100A9+ cells) rather than in neurons or microglia, and its inhibition significantly reduced astrocyte activation (GFAP+ cells), reversed A1 astrocyte gene upregulation (H2-D1, C3, Serping1), and increased A2 astrocyte gene expression (Emp1, P …

Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer's Disease.

Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer's disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with (n = 42) AD, (n = 18) mild cognitive impairment (MCI) and (n = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinf

The Effect of the Optogenetic Stimulation of Astrocytes on Neural Network Activity in an In Vitro Model of Alzheimer's Disease.

Optogenetics is a combination of optical and genetic technologies used to activate or, conversely, inhibit specific cells in living tissues. The possibilities of using optogenetics approaches for the treatment of epilepsy, Parkinson's and Alzheimer's disease (AD) are being actively researched. In recent years, it has become clear that one of the most important players in the development of AD is astrocytes. Astrocytes affect amyloid clearance, participate in the development of neuroinflammation, and regulate the functioning of neural networks. We used an adeno-associated virus carrying the gli…

Conservation of neuron-astrocyte coordinated activity among sensory processing centers of the developing brain.

Afferent neurons in developing sensory organs exhibit a prolonged period of burst firing prior to the onset of sensory experience. This intrinsically generated activity propagates from the periphery through central processing centers to promote the survival and physiological maturation of neurons and refine their synaptic connectivity. Recent studies in the auditory system indicate that these bursts of action potentials also trigger metabotropic glutamate receptor-mediated calcium increases within astrocytes that are spatially and temporally correlated with neuronal events; however, it is not …

Mesencephalic Astrocyte-derived Neurotrophic Factor Supports Hepatitis B Virus-induced Immunotolerance.

BACKGROUND & AIMS: The immune tolerance induced by hepatitis B virus (HBV) is a major challenge for achieving effective viral clearance, and the mechanisms involved are not well-understood. One potential factor involved in modulating immune responses is mesencephalic astrocyte-derived neurotrophic factor (MANF), which has been reported to be increased in patients with chronic hepatitis B. In this study, our objective is to examine the role of MANF in regulating immune responses to HBV. METHODS: We utilized a commonly used HBV-harboring mouse model, where mice were hydrodynamically injected wi