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Expression of proinflammatory molecules by glial cells is involved in the pathophysiological changes associated with chronic neurological diseases. Under pathological conditions, astrocytes release a number of proinflammatory molecules, such as interleukin‐6 (IL‐6) and interferon‐γ‐inducible protein‐10 (IP‐10). The ovarian hormone estradiol exerts protective effects in the central nervous system that,...
Microglia express Toll‐like receptors (TLRs) that recognize invading pathogens as well as endogenous proteins such as fibronectin under nonphysiological conditions. Here, we demonstrated that fibronectin stimulates murine microglia in culture in a dose‐dependent manner: microglial cells secreted proinflammatory cytokines and chemokines and increased phagocytosis of Escherichia coli DH5α and E. coli...
We previously demonstrated that transforming growth factor‐β1 (TGF‐β1), while having no effect alone, enhances nitric oxide (NO) production in primary, purified mouse astrocytes induced by lipopolysaccharide (LPS) plus interferon‐γ (IFN‐γ), by recruiting a latent population of astrocytes to respond, thereby enhancing the total number of cells that express Nos2. In this investigation, we evaluated...
In the brain, translocator protein (18 kDa) (TSPO), previously called peripheral benzodiazepine receptor (PBR), is a glial protein that has been extensively used as a biomarker of brain injury and inflammation. However, the functional role of TSPO in glial cells is not well characterized. In this study, we show that the TSPO‐specific ligands R‐PK11195 (PK) and Ro5‐4864 (Ro) increased microglia proliferation...
There is increasing evidence that astrocytes play important roles in immune regulation in the brain. Astrocytes express toll‐like receptors (TLR) and build up responses to innate immune triggers by releasing proinflammatory molecules. We investigate signaling pathways and released molecules after astrocyte TLR4 activation. Purified rodent brain astrocyte cultures were treated with the TLR4 activator...
Sex‐related differences have been observed in the incidence and severity of several neurological diseases and in sepsis in humans. Cyclic adenosine monophosphate (cAMP) has been shown to play an important role in modulating the inflammatory environment during neuroinflammation and importantly in protecting myelin from excitotoxic cell death. Considering the sexual dimorphism in the functional properties...
Recently, neurotransmitters/neurohormones have been identified as factors controlling the function of microglia, the immune competent cells of the central nervous system. In this study, we compared the responsiveness of microglia to neurotransmitters/neurohormones. We freshly isolated microglia from healthy adult C57Bl/6 mice and found that only a small fraction (1–20%) responded to the application...
Inflammation is a common component of acute injuries of the central nervous system (CNS) such as ischemia, and degenerative disorders such as Alzheimer's disease. Glial cells play important roles in local CNS inflammation, and an understanding of the roles for microRNAs in glial reactivity in injury and disease settings may therefore lead to the development of novel therapeutic interventions. Here,...
Microglia, the major immune cells in central nervous system, act as the surveillance and scavenger of immune defense and inflammatory response. Previous studies suggest that there might be close relationship between acid‐sensing ion channels (ASICs) and inflammation, however, the exact role of ASICs in microglia during inflammation remains elusive. In the present study, we identified the existence...
Sleep‐wake behavior is altered in response to immune challenge. Although the precise mechanisms that govern sickness‐induced changes in sleep are not fully understood, interleukin‐1β (IL‐1) is one mediator of these responses. To better understand mechanisms underlying sleep and inflammatory responses to immune challenge, we used two transgenic mouse strains that express IL‐1 receptor 1 (IL1R1) only...
Microglia, the immune cells of the CNS, are highly adaptive cells that can acquire different pro‐ and anti‐inflammatory activation states with distinct functions in CNS homeostasis and pathologies. To study microglial function in vitro, primary microglia or immortalized cell lines are commonly used. An alternative to these cells are embryonic stem cell‐derived microglia (ESdM). ESdM have previously...
Severe peripheral infections induce an adaptive sickness behavior and an innate immune reaction in various organs including the brain. On the long term, persistent alteration of microglia, the brain innate immune cells, is associated with an increased risk of psychiatric disorders. It is thus critical to identify genes and mechanisms controlling the intensity and duration of the neuroinflammation...
Glial activation with the production of pro‐inflammatory mediators is a major driver of disease progression in neurological processes ranging from acute traumatic injury to chronic neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. Posttranscriptional regulation is a major gateway for glial activation as many mRNAs encoding pro‐inflammatory mediators contain...
Gamma‐aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the brain, affects numerous immune cell functions. Microglia, the brain's resident innate immune cells, regulate GABA signaling through GABA receptors and express the complete GABAergic machinery for GABA synthesis, uptake, and release. Here, the use of primary microglial cell cultures and ex vivo brain tissue sections allowed...
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