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The interleukin (IL)‐6/gp130 family of cytokines (e.g., IL‐6, IL‐11, leukemia inhibitory factor (LIF) and oncostatin M (OSM)) play important roles in the central nervous system (CNS) during neuroinflammation and neurodevelopment. However, little is known regarding the responses by astroglia and microglia to this family of cytokines. Here the expression of the IL‐6/gp130 cytokine receptors and subsequent...
The endocannabinoids 2‐araquidonoylglycerol (2‐AG) and anandamide (AEA) are bioactive lipids crucially involved in the regulation of brain function in basal and pathological conditions. Blockade of endocannabinoid metabolism has emerged as a promising therapeutic strategy for inflammatory diseases of the central nervous system, including myelin disorders such as multiple sclerosis. Nevertheless, the...
Milk fat globule‐epidermal growth factor‐factor 8 (Mfge8) has been described as an essential molecule during microglia‐mediated clearance of apoptotic cells via binding to phosphatidylserine residues and subsequent phagocytosis. Impaired uptake of apoptotic cells by microglia results in prolonged inflammatory responses and damage of healthy cells. Although the mechanisms of Mfge8‐mediated engulfment...
Glycogen phosphorylase (GP) is activated to degrade glycogen in response to different stimuli, to support both the astrocyte's own metabolic demand and the metabolic needs of neurons. The regulatory mechanism allowing such a glycogenolytic response to distinct triggers remains incompletely understood. In the present study, we used siRNA‐mediated differential knockdown of the two isoforms of GP expressed...
Hepatic encephalopathy (HE) is a frequent complication of liver cirrhosis and is due to a low‐grade cerebral edema associated with oxidative/nitrosative stress. Recent reports suggest that cognitive impairment in cirrhotic patients may not resolve completely after an attack of manifest HE. As astrocyte dysfunction is central to the pathogenesis of HE and astrocytes are critically involved in synaptic...
Microglia and astroglia play critical roles in the development, function, and survival of neurons in the CNS. However, under inflammatory conditions the role of astrogliosis in the inflammatory process and its effects on neurons remains unclear. Here, we used several types of cell cultures treated with the bacterial inflammogen LPS to address these questions. We found that the presence of astroglia...
Genetic targeting of microglia and other myeloid cells in the central nervous system (CNS) is highly desirable as they are critical effectors and regulators of changes in CNS homeostasis during development as well as in health and disease. Therefore, genetic reprogramming of microglia could constitute a central approach for potentially reducing disease burden. Previous attempts to target only microglia...
Seizures frequently accompany gliomas and often escalate to peritumoral epilepsy. Previous work revealed the importance of tumor‐derived excitatory glutamate (Glu) release mediated by the cystine‐glutamate transporter (SXC) in epileptogenesis. We now show a novel contribution of GABAergic disinhibition to disease pathophysiology. In a validated mouse glioma model, we found that peritumoral parvalbumin‐positive...
The central nervous system (CNS) of terrestrial vertebrates underwent a prominent molecular change when proteolipid protein (PLP) replaced P0 protein as the most abundant protein of CNS myelin. However, PLP did not replace P0 in peripheral nervous system (PNS) myelin. To investigate the possible consequences of a PLP to P0 shift in PNS myelin, we engineered mice to express PLP instead of P0 in PNS...
Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of...
Apolipoprotein E (apoE) is well known as a regulator of cholesterol homeostasis, and is increasingly recognized to play a prominent role in the modulation of innate immune response, including cell‐to‐cell communication and migration. Alzheimer's disease (AD) is a slowly progressive neurodegenerative disorder characterized by neuroinflammation that appears to be an important component of the pathophysiology...
Waves of spreading depolarization (SD) have been implicated in the progressive expansion of acute brain injuries. SD can persist over several days, coincident with the time course of astrocyte activation, but little is known about how astrocyte activation may influence SD susceptibility. We examined whether activation of astrocytes modified SD threshold in hippocampal slices. Injection of a lentiviral...
Tryptophan catabolism is increasingly recognized as a key and druggable molecular mechanism active in cancer, immune, and glioneural cells and involved in the modulation of antitumor immunity, autoimmunity and glioneural function. In addition to the pivotal rate limiting enzyme indoleamine‐2,3‐dioxygenase, expression of tryptophan‐2,3‐dioxygenase (TDO) has recently been described as an alternative...
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