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Glial cell activation plays an important role in the pathogenesis of various neurodegenerative disorders as well as in chronic and neuropathic pain. This chapter describes a model which allows one to assess the individual and combined contributions of astrocytes and microglia in response to a pro-inflammatory stimulus, with emphasis on ionotropic purinergic receptors.
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http://dx.doi.org/10.1007/978-1-4939-7571-6_10 | DOI Listing |
Neuron
June 2025
Ann Romney Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. Electronic address:
Genetic studies implicate clusterin (CLU) in the pathogenesis of Alzheimer's disease (AD), yet its precise molecular impact remains unclear. Through unbiased proteomic profiling and functional validation in CLU-deficient astrocytes, we identify increased nuclear factor κB (NF-κB)-dependent signaling and complement C3 secretion. Reduction of astrocyte CLU induced microglia-dependent modulation of extracellular apolipoprotein E (APOE) and phosphorylated tau, as well as increased microglial phagocytosis and reduced synapse numbers.
View Article and Find Full Text PDFFront Psychiatry
March 2025
Department of Neurology, Klinikum Vest, Academic Teaching Hospital of the Ruhr University Bochum, Recklinghausen, Germany.
Schizophrenia is a severe mental disorder with a strong lifetime impact on patients' health and wellbeing. Usually, symptomatic treatment includes typical or atypical antipsychotics. Study findings show an involvement of low-grade inflammation (blood, brain parenchyma, and cerebrospinal fluid) in schizophrenia.
View Article and Find Full Text PDFResearch (Wash D C)
January 2025
Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.
Sepsis-associated encephalopathy (SAE) is a severe and frequent septic complication, characterized by neuronal damage as key pathological features. The astrocyte-microglia crosstalk in the central nervous system (CNS) plays important roles in various neurological diseases. However, how astrocytes interact with microglia to regulate neuronal injury in SAE is poorly defined.
View Article and Find Full Text PDFFront Toxicol
January 2025
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, United States.
Primary cell cultures from rodent brain are widely used to investigate molecular and cellular mechanisms of neurotoxicity. To date, however, it has been challenging to reliably culture endogenous microglia in dissociated mixed cultures. This is a significant limitation of most neural cell models given the growing awareness of the importance of interactions between neurons, astrocytes and microglia in defining responses to neurotoxic exposures.
View Article and Find Full Text PDFJ Alzheimers Dis
December 2024
Department of Electrical and Computer Engineering, University of California-Davis, Davis, CA, USA.
Background: Microglia play a critical role in neurodegenerative disorders, such as Alzheimer's disease, where alterations in microglial function may result in pathogenic amyloid-β (Aβ) accumulation, chronic neuroinflammation, and deleterious effects on neuronal function. However, studying these complex factors in vivo, where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of critical cell types in the same culture.
Objective: We employed a rat primary tri-culture (neurons, astrocytes, and microglia) model and compared it to co-culture (neurons and astrocytes) and mono-culture (microglia) to study microglial function (i.