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Diffuse midline glioma (DMG) is a type of lethal brain tumor that develops mainly in children. The majority of DMG harbor the K27M mutation in histone H3. Oligodendrocyte progenitor cells (OPCs) in the brainstem are candidate cells‐of‐origin for DMG, yet there is no genetically engineered mouse model of DMG initiated in OPCs. Here, we used the RCAS/Tv‐a avian retroviral system to generate DMG in Olig2‐expressing...
Neuron–microglia communication through the Cx3cr1–Cx3cl1 axis is essential for the development and refinement of neural circuits, which determine their function into adulthood. In the present work we set out to extend the behavioral characterization of Cx3cr1−/− mice evaluating innate behaviors and spatial navigation, both dependent on hippocampal function. Our results show that Cx3cr1‐deficient mice,...
Synaptic elements from neuromuscular junctions (NMJs) undergo massive morphological and functional changes upon nerve injury. While morphological changes of NMJ‐associated glia in response to injury has been investigated, their functional properties remain elusive. Perisynaptic Schwann cells (PSCs), glial cells at the NMJ, are essential for NMJ maintenance and repair, and are involved in synaptic...
Exposure of microglia to an inflammatory environment may lead to their priming and exacerbated response to future inflammatory stimuli. Here we aimed to explore hypothalamic microglia priming and its consequences on energy balance regulation. A model of intracerebroventricular administration of neuraminidase (NA, which is present in various pathogens such as influenza virus) was used to induce acute...
Norepinephrine exerts powerful influences on the metabolic, neuroprotective and immunoregulatory functions of astrocytes. Until recently, all effects of norepinephrine were believed to be mediated by receptors localized exclusively to the plasma membrane. However, recent studies in cardiomyocytes have identified adrenergic receptors localized to intracellular membranes, including Golgi and inner nuclear...
Schizophrenia is a complex, chronic mental health disorder whose heterogeneous genetic and neurobiological background influences early brain development, and whose precise etiology is still poorly understood. Schizophrenia is not characterized by gross brain pathology, but involves subtle pathological changes in neuronal populations and glial cells. Among the latter, astrocytes critically contribute...
Retinal neovascularization (NV) is the major cause of severe visual impairment in patients with ischemic eye diseases. While it is known that retinal microglia contribute to both physiological and pathological angiogenesis, the molecular mechanisms by which these glia regulate pathological NV have not been fully elucidated. In this study, we utilized a retinal microglia‐specific Transforming Growth...
Cover Illustration: Tgfbr2‐deficient microglia (upper panel) transform to an activated state and a dramatically different localization and morphology compared to microglia in control eyes (lower panel). Four weeks after tamoxifen induction of Tgfbr2 KO (ΔMG), Tgfbr2 deficient microglia (red stain with IBA1 antibody) tightly adhered to retinal vessels (blue stain with GS lectin) in the outer retinal...
Microglia play many critical roles in neural development. Recent single‐cell RNA‐sequencing studies have found diversity of microglia both across different stages and within the same stage in the developing brain. However, how such diversity is controlled during development is poorly understood. In this study, we first found the expression of the macrophage mannose receptor CD206 in early‐stage embryonic...
Preterm infants often show pathologies of the cerebellum, which are associated with impaired motor performance, lower IQ and poor language skills at school ages. Using a mouse model of inflammation‐induced encephalopathy of prematurity driven by systemic administration of pro‐inflammatory IL‐1β, we sought to uncover causes of cerebellar damage. In this model, IL‐1β is administered between postnatal...
Mechanisms regulating oligodendrocyte differentiation, developmental myelination and myelin maintenance in adulthood are complex and still not completely described. Their understanding is crucial for the development of new protective or therapeutic strategies in demyelinating pathologies such as multiple sclerosis. In this perspective, we have investigated the role of Cyclin‐dependent kinase 7 (Cdk7),...
Astrocytes are glial cells that serve homeostatic functions in the central nervous system (CNS). Recent research, however, suggests that under pathological conditions, astrocytes are stimulated by various factors and actively participate in CNS inflammation. In the present study, we found that astrocytes upregulate various inflammatory factors including prostaglandin E2 (PGE2) by co‐stimulation with...
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