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Targeting Reactive Astrocytes with Flavonoids to Alleviate Neuroinflammation and Promote Synaptic Function.

Astrocytes are central regulators of neural homeostasis, synaptic function, and neuroinflammatory responses in the central nervous system (CNS). Upon pathological stimuli, astrocytes undergo reactive transformations, producing pro-inflammatory cytokines, reactive oxygen species (ROS), and chemokines, which exacerbate neuronal injury. Flavonoids, a diverse class of polyphenolic compounds found in fruits, vegetables, and medicinal plants, have emerged as potent modulators of astrocyte activity, promoting neuroprotection and cognitive enhancement. These compounds, including quercetin, hesperetin,…

Old dog, new tricks: Astrocytes use the CD40 pathway to propagate neuroinflammation.

In addition to myeloid antigen-presenting cells (APCs), CD40 also induces APC potential in astrocytes during neuroinflammation.

Astrocytes mediate the dopaminergic modulation of tonic GABAergic signaling in substantia nigra.

Recent studies have implicated dopaminergic signaling within the substantia nigra pars reticulata (SNr) in the emergence of Parkinsonian mot … rons. In contrast, the ability of D2R agonists to disinhibit SNr neurons depended on D2R-expressing astrocytes and stimulation of GAT-3 uptake of GABA from the extracellular space. In addition to underscoring the importance of dendritically released dopamine in modulating synaptic transmission, our studies demonstrate that dopaminergic modulation of astrocyt …

Yin Yang 1 Specifically Supports the Development of Olig2 Positive Cerebellar Astrocytes.

Astrocytes regulate the assembly and functions of neural circuits, contribute to synaptic homeostasis, provide metabolic support to neurons, and control ion balance and blood-brain barrier integrity. These cells are morphologically and molecularly very heterogeneous and perform unique functions to accommodate the needs of subsets of neurons. In this study, we identified and characterized a subpopulation of cerebellar astrocytes expressing the transcription factor Olig2 (O2AST). We defined their molecular identity and transcriptional divergence from other well-established subpopulations of cere…

Astrocytes orchestrate neuroprotection and pathogenesis via bidirectional neuronal interactions in Parkinson's disease.

Parkinson's disease (PD), a prevalent neurodegenerative disorder, is characterized by the degeneration of dopaminergic neurons in the substantia nigra and striatum of the midbrain, manifesting as distinct motor impairments. While conventional theories attribute PD's development to neuronal damage, astrocytes have garnered significant attention for their potential protective role. As the most abundant glial cells in the central nervous system (CNS), astrocytes may exert neuroprotective effects through mechanisms including secretion of neurotrophic factors, regulation of the blood-brain barrier …

Singlet oxygen controls vasodilation through the activation of calcium signalling in astrocytes.

The central nervous system is highly active and one of the fastest consumers of oxygen. Thus, the brain requires immediate and effective oxygenation by arterial blood supply. Singlet oxygen is a non-radical form of oxygen which can be produced in cells by non-enzymatic and enzymatic means. Generation of non-toxic doses of singlet oxygen in a primary co-culture of neurons and astrocytes by 1267 nm laser induces calcium signalling in astrocytes via the induction of lipid peroxidation, activation of phospholipase C and production of IP3. [Ca2+]i rise in astrocytes triggers fusion of vesicular com…

Interactions between astrocytes and cerebral endothelial cells in central nervous system diseases.

Endothelial cells and astrocytes are the two main types of cells in the blood-brain barrier, and each plays a pivotal role in the central nervous system. Although they have different functional characteristics, they can mutually communicate and cooperate with each other to maintain the normal function of the neurovascular unit and are substantially altered during pathology. Understanding the relationship between astrocytes and endothelial cells can lay the foundation for advancing protective therapies against central nervous system diseases. From a new perspective of the interactions between e…

SerpinA3N-APOE interaction in astrocytes exacerbates Alzheimer's disease progression through NFκB activation.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders characterized by β-amyloid (Aβ) deposition, neurofibrillary tangles, neuronal loss, and neuroinflammation. It represents a growing global health crisis. Although astrocytes contribute to neuroinflammatory cascades, their molecular regulators in AD progression remains elusive. Here, through single-cell transcriptomic analysis, we identified SerpinA3N as a disease-progressive modulator upregulated in AD astrocytes, with expression levels correlating with pathological severity. Astrocytic SerpinA3N knockdown in AD m…

Cortical reactive microglia activate astrocytes, increasing neurodegeneration in human alcohol use disorder.

Reactive microglia are associated with multiple brain diseases that may have specific disease-related phenotypes. Studies of human cortical … ce reactive microglia are linked to increased glial fibrillary acid protein (GFAP + IR) in reactive astrocytes, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG + IR), and neuron loss, these were determined as well. AUD reactive microglia were identified by increases in expression of multiple markers in the OFC compared to control moderate drinkers. …

Topoisomerase IIα-mediated stemness response in reactive astrocytes to traumatic brain injury.

Rationale: As a highly plastic population, parenchymal astrocytes have demonstrated the capacity to become activated and recapitulate neurogenic potential in response to traumatic central nervous system (CNS) injuries, representing a latent reservoir for neuronal regeneration in non-neurogenic brain regions. However, the extrinsic and intrinsic factors regulating this process remain poorly characterized. Elucidating these molecular mechanisms is crucial to harnessing the regenerative potential of reactive astrocytes in CNS repair. Methods: A multidisciplinary approach combining immunostaining,…

Consumption of L-Proline as Energy Substrate by Cultured Primary Rat Astrocytes.

The catabolism of the proteinogenic amino acid L-proline in mammalian cells is mediated by mitochondrial enzymes that can oxidize proline to provide energy for mitochondrial ATP regeneration. To investigate the potential of astrocytes to consume and metabolize L-proline, we incubated cultured primary rat astrocytes with L-proline in the absence or the presence of other energy substrates and investigated L-proline consumption, cellular ATP content and cell viability. In the absence of glucose, the cells consumed L-proline which allowed the cells to maintain a high cellular ATP level as long as …

Akkermansia моноколонизация модифицирует микроглию и астроциты конкретным штаммом.

Микроглиа и астроциты являются основными глиальными клетками центральной нервной системы (КНС), и их функция определяется множеством факторов. Поступили сообщения о регулировании CNS glia микробиотой, хотя роль конкретных бактерий не была определена. Мы колонизировали мышей, свободных от микробов, с штаммом Akkermansia muciniphila (AmT) и романом A. muciniphila штамм BWH-H3 (Am-H3), изолированным от предмета с множественным склерозом, и по сравнению с мышами, колонизированными с штаммом BWH-E5 (Bc), изолированными от здорового контрольного предмета. Затем мы изучили влияние этих бактерий на ми

Совпадение в аннотации оригинала
Microglia and astrocytes are the primary glial cells in the central nervous system (CNS) and their function is shaped by multiple factors. Regulation of CNS glia by the microbiota have been reported, although the role of specific bacteria has not been identified. We colonized germ-free mice with the type strain Akkermansia muciniphila (AmT) and a novel A. mu…

Comparative Transcriptomic Analysis of Cerebellar Astrocytes across Developmental Stages and Brain Regions.

Astrocytes are the most abundant glial cell type in the central nervous system, and they play a crucial role in normal brain function. While gliogenesis and glial differentiation occur during perinatal cerebellar development, the processes that occur during early postnatal development remain obscure. In this study, we conducted transcriptomic profiling of postnatal cerebellar astrocytes at postnatal days 1, 7, 14, and 28 (P1, P7, P14, and P28), identifying temporal-specific gene signatures at each specific time point. Comparing these profiles with region-specific astrocyte differentially expre…

Bioinformatics analysis reveals multiple functional changes in astrocytes in temporal lobe epilepsy.

Epilepsy is a prevalent chronic neurological disorder characterized by recurrent seizures and brain dysfunction. Existing antiepileptic drugs (AEDs) mainly act on neurons and provide symptomatic control of seizures, but they do not modify the progression of epilepsy and may cause serious adverse effects. Increasing evidence suggests that reactive astrogliosis is critical in the pathophysiology of epilepsy. However, the function of reactive astrocytes in epilepsy has not been thoroughly explored. To provide a new perspective on the role of reactive astrocytes in epileptogenesis, we identified h…

Iron deficiency in astrocytes alters cellular status and impacts on oligodendrocyte differentiation.

Iron deficiency (ID) has been shown to affect central nervous system (CNS) development and induce hypomyelination. Previous work from our laboratory in a gestational ID model showed that both oligodendrocyte (OLG) and astrocyte (AST) maturation was impaired. To explore the contribution of AST iron to the myelination process, we generated an in vitro ID model by silencing divalent metal transporter 1 (DMT1) in AST (siDMT1 AST) or treating AST with Fe3+ chelator deferoxamine (DFX; DFX AST). siDMT1 AST showed no changes in proliferation but remained immature. Co-cultures of oligodendrocyte precur

Carnosine ameliorates postoperative cognitive dysfunction of aged rats by limiting astrocytes pyroptosis.

Postoperative cognitive dysfunction (POCD) is a common postoperative complication in elderly patients, and neuroinflammation is a key hallmark. Recent studies suggest that the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated astrocytes pyroptosis is involved in the regulation of neuroinflammation in many neurocognitive diseases, while its role in POCD remains obscure. Carnosine is a natural endogenous dipeptide with anti-inflammatory and neuroprotective effects. To explore the effect of carnosine on POCD and its mechanism, we established a POCD model by explora…

Astrocytes in preoptic area regulate acute nociception-induced hypothermia through adenosine receptors.

AIMS: The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects body temperature and its mechanism remains poorly studied. METHODS: We used capsaicin, formalin, and surgery to induce acute nociceptive stimulation and monitored rectal temperature. Optical fiber recording, chemical genetics, confocal imaging, and pharmacology assays were employed to confirm the role and interaction of POA astrocytes and extracellular adenosine. Immunofluorescence was utilized for further validation. R…

Aberrant activation of hippocampal astrocytes causes neuroinflammation and cognitive decline in mice.

Reactive astrocytes are associated with neuroinflammation and cognitive decline in diverse neuropathologies; however, the underlying mechanisms are unclear. We used optogenetic and chemogenetic tools to identify the crucial roles of the hippocampal CA1 astrocytes in cognitive decline. Our results showed that repeated optogenetic stimulation of the hippocampal CA1 astrocytes induced cognitive impairment in mice and decreased synaptic long-term potentiation (LTP), which was accompanied by the appearance of inflammatory astrocytes. Mechanistic studies conducted using knockout animal models and hi…

Glutamate Provides Cytoprotective Effect for Astrocytes Against Ischemic Insult and Promotes Astrogliosis.

Glutamate-mediated excitotoxicity has been extensively explored as a therapeutic target for the development of potential treatments of neurological disorders including stroke. However, the effect of glutamate on astrocytes under pathological conditions has been less studied. Using primary astrocyte culture, we determined the effect of glutamate on astrocytes against ischemic insult. Glutamate provided a cytoprotective effect and acted as an alternative substrate for ATP production in primary astrocytes against oxygen glucose deprivation reoxygenation insult, which was blocked by glutamate upta…

Astrocytes control quiescent NSC reactivation via GPCR signaling-mediated F-actin remodeling.

The transitioning of neural stem cells (NSCs) between quiescent and proliferative states is fundamental for brain development and homeostasi … g, G-protein αq subunit, Rho1 GTPase, and Diaphanous (Dia)/Formin during NSC reactivation. Further, astrocytes secrete a Smog ligand Fog to regulate Gαq-Rho1-Dia-mediated NSC reactivation. Together, we establish that the Smog-Gαq-Rho1 signaling axis derived from astrocytes, a NSC niche, regulates Dia-mediated F-actin dynamics in NSC reactivation.