Search results for "glia"
showing 10 items of 1274 documents
Lipoprotein receptor loss in forebrain radial glia results in neurological deficits and severe seizures.
2020
The Alzheimer disease-associated multifunctional low-density lipoprotein receptor-related protein-1 is expressed in the brain. Recent studies uncovered a role of this receptor for the appropriate functioning of neural stem cells, oligodendrocytes, and neurons. The constitutive knock-out (KO) of the receptor is embryonically lethal. To unravel the receptors' role in the developing brain we generated a mouse mutant by specifically targeting radial glia stem cells of the dorsal telencephalon. The low-density lipoprotein receptor-related protein-1 lineage-restricted KO female and male mice, in contrast to available models, developed a severe neurological phenotype with generalized seizures duri…
Differential role of interleukin-1β in neuroinflammation-induced impairment of spatial and nonspatial memory in hyperammonemic rats.
2019
Activated microglia and increased brain IL-1β play a main role in cognitive impairment in much pathology. We studied the role of IL-1β in neuroinflammation-induced impairment of the following different types of learning and memory: novel object recognition (NOR), novel object location (NOL), spatial learning, reference memory (RM), and working memory (WM). All these processes are impaired in hyperammonemic rats. We assessed which of these types of learning and memory are restored by blocking the IL-1 receptor in vivo in hyperammonemic rats and the possible mechanisms involved. Blocking the IL-1 receptor reversed microglial activation in the hippocampus, perirhinal cortex, and prefrontal cor…
Social stress during adolescence activates long-term microglia inflammation insult in reward processing nuclei
2018
The experience of social stress during adolescence is associated with higher vulnerability to drug use. Increases in the acquisition of cocaine self-administration, in the escalation of cocaine-seeking behavior, and in the conditioned rewarding effects of cocaine have been observed in rodents exposed to repeated social defeat (RSD). In addition, prolonged or severe stress induces a proinflammatory state with microglial activation and increased cytokine production. The aim of the present work was to describe the long-term effects induced by RSD during adolescence on the neuroinflammatory response and synaptic structure by evaluating different glial and neuronal markers. In addition to an inc…
Oligodendrocytes support axonal transport and maintenance via exosome secretion
2020
Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of axons depends on intrinsic mechanisms including axonal transport and extrinsic support from adjacent glial cells. The mechanisms of support provided by myelinating oligodendrocytes to underlying axons are only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties of exosomes, which upon delivery to neurons improve neuronal viability in vitro. Here, we show that oligodendroglial exosome secretion is impaired in 2 mouse mutants exhibiting secondary axonal degeneration due to oligodendrocyte-specific gene defects. Wild-type oligodendroglial exosomes …
The Cumulative Effect of Transient Synchrony States on Motor Performance in Parkinson's Disease.
2020
Bursts of beta frequency band activity in the basal ganglia of patients with Parkinson's disease (PD) are associated with impaired motor performance. Here we test in human adults whether small variations in the timing of movement relative to beta bursts have a critical effect on movement velocity and whether the cumulative effects of multiple beta bursts, both locally and across networks, matter.
Dietary salt promotes ischemic brain injury and is associated with parenchymal migrasome formation
2018
Sodium chloride promotes vascular fibrosis, arterial hypertension, pro-inflammatory immune cell polarization and endothelial dysfunction, all of which might influence outcomes following stroke. But despite enormous translational relevance, the functional importance of sodium chloride in the pathophysiology of acute ischemic stroke is still unclear. In the current study, we show that high-salt diet leads to significantly worse functional outcomes, increased infarct volumes, and a loss of astrocytes and cortical neurons in acute ischemic stroke. While analyzing the underlying pathologic processes, we identified the migrasome as a novel, sodium chloride-driven pathomechanism in acute ischemic …
Glia to neuron ratio in the posterior aspect of the human spinal cord at thoracic segments relevant to spinal cord stimulation.
2019
Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, interse…
Short-Term Effects of Microglia-Specific Mitochondrial Dysfunction on Amyloidosis in Transgenic Models of Alzheimer's Disease.
2018
Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer’s disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging. To study the impact of mitochondrial alterations on microglial activity in a homogeneous genetic background, we generated bone marrow chimeras of irradiated 46-days-old APP-transgenic mice. For reconstitution, bone marrow from CX3CR1-eGFP mice with mitochondria of either non-obese diabetic or C57BL/6J animals was utilized. Succes…
Oligodendrocytes Provide Antioxidant Defense Function for Neurons by Secreting Ferritin Heavy Chain.
2020
An evolutionarily conserved function of glia is to provide metabolic and structural support for neurons. To identify molecules generated by glia and with vital functions for neurons, we used Drosophila melanogaster as a screening tool, and subsequently translated the findings to mice. We found that a cargo receptor operating in the secretory pathway of glia was essential to maintain axonal integrity by regulating iron buffering. Ferritin heavy chain was identified as the critical secretory cargo, required for the protection against iron-mediated ferroptotic axonal damage. In mice, ferritin heavy chain is highly expressed by oligodendrocytes and secreted by employing an unconventional secret…
Mast cells are associated with the onset and progression of celiac disease
2017
Background Celiac disease (CD) is an immune-mediated disorder characterized by an accumulation of immune cells in the duodenal mucosa as a consequence of both adaptive and innate immune responses to undigested gliadin peptides. Mast cells (MCs) are innate immune cells that are a major source of costimulatory signals and inflammatory mediators in the intestinal mucosa. Although MCs have previously been associated with CD, functional studies have never been performed. Objective We aimed at evaluating the role of MCs in the pathogenesis of CD. Methods Intestinal biopsy specimens of patients with CD were scored according to the Marsh classification and characterized for leukocyte infiltration a…