Prior epigenetic status predicts future susceptibility to seizures in mice.

Wide variation of responses to identical stimuli presented to genetically inbred mice suggests the hypothesis that stochastic epigenetic variation during neurodevelopment can mediate such phenotypic differences. However, this hypothesis is largely untested since capturing pre-existing molecular states requires non-destructive, longitudinal recording. Therefore, we tested the potential of Calling Cards (CC) to record transient neuronal enhancer activity during postnatal development, and thereby associate epigenetic variation with a subsequent phenotypic presentation - degree of seizure response to the pro-convulsant pentylenetetrazol.

Investigating the NLRP3 inflammasome and its regulator miR-223-3p in multiple sclerosis and experimental demyelination.

Innate immune signaling pathways are essential mediators of inflammation and repair following myelin injury. Inflammasome activation has recently been implicated as a driver of myelin injury in multiple sclerosis (MS) and its animal models, although the regulation and contributions of inflammasome activation in the demyelinated central nervous system (CNS) are not completely understood. Herein, we investigated the NLRP3 (NBD-, LRR- and pyrin domain-containing protein 3) inflammasome and its endogenous regulator microRNA-223-3p within the demyelinated CNS in both MS and an animal model of focal demyelination.

TAAR1 Expression in Human Macrophages and Brain Tissue: A Potential Novel Facet of MS Neuroinflammation.

TAAR1 is a neuroregulator with emerging evidence suggesting a role in immunomodulation. Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. Here, we investigate TAAR1 expression in human primary monocytes, peripherally-derived macrophages, and MS brain tissue.

Interleukin-1 receptor antagonist: An exploratory plasma biomarker that correlates with disability and provides pathophysiological insights in relapsing-remitting multiple sclerosis.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disorder. Interleukin-1 receptor antagonist (IL-1RA) is an endogenous soluble antagonist of the IL-1 receptor and blocks the pro-inflammatory effects of IL-1β known to contribute to MS pathology. The objectives of this study were to determine whether IL-1RA is associated with disability in MS and how this correlates with neurofilament light (NfL) levels in cerebrospinal fluid (CSF).

Inhibitory milieu at the multiple sclerosis lesion site and the challenges for remyelination.

Regeneration of myelin, following injury, can occur within the central nervous system to reinstate proper axonal conductance and provide trophic support. Failure to do so renders the axons vulnerable, leading to eventual degeneration, and neuronal loss. Thus, it is essential to understand the mechanisms by which remyelination or failure to remyelinate occur, particularly in the context of demyelinating and neurodegenerative disorders.

MicroRNA-223 protects neurons from degeneration in experimental autoimmune encephalomyelitis.

Multiple sclerosis is a chronic inflammatory, demyelinating, and neurodegenerative disease affecting the brain, spinal cord and optic nerves. Neuronal damage is triggered by various harmful factors that engage diverse signalling cascades in neurons; thus, therapeutic approaches to protect neurons will need to focus on agents that can target multiple biological processes. We have therefore focused our attention on microRNAs: small non-coding RNAs that primarily function as post-transcriptional regulators that target messenger RNAs and repress their translation into proteins.

Corrigendum: Phagocytosis in the Brain: Homeostasis and Disease.

[This corrects the article DOI: 10.3389/fimmu.2019.

Phagocytosis in the Brain: Homeostasis and Disease.

Microglia are resident macrophages of the central nervous system and significantly contribute to overall brain function by participating in phagocytosis during development, homeostasis, and diseased states. Phagocytosis is a highly complex process that is specialized for the uptake and removal of opsonized and non-opsonized targets, such as pathogens, apoptotic cells, and cellular debris. While the role of phagocytosis in mediating classical innate and adaptive immune responses has been known for decades, it is now appreciated that phagocytosis is also critical throughout early neural development, homeostasis, and initiating repair mechanisms.

miR-223 promotes regenerative myeloid cell phenotype and function in the demyelinated central nervous system.

In the injured central nervous system, myeloid cells, including macrophages and microglia, are key contributors to both myelin injury and repair. This immense plasticity emphasizes the need to further understand the precise molecular mechanisms that contribute to the dynamic regulation of myeloid cell polarization and function. Herein, we demonstrate that miR-223 is upregulated in multiple sclerosis (MS) patient monocytes and the alternatively-activated and tissue-regenerating M2-polarized human macrophages and microglia.

The roles of extracellular vesicle microRNAs in the central nervous system.

MicroRNAs (miRNAs) are small, highly conserved non-coding RNA molecules that post-transcriptionally regulate protein expression and most biological processes. Mature miRNAs are recruited to the RNA-induced silencing complex (RISC) and target mRNAs via complementary base-pairing, thus resulting in translational inhibition and/or transcript degradation. Here, we present evidence implicating miRNAs within extracellular vesicles (EVs), including microvesicles and exosomes, as mediators of central nervous system (CNS) development, homeostasis, and injury.

Effects of fumarates on inflammatory human astrocyte responses and oligodendrocyte differentiation.

Objective: Dimethyl fumarate (DMF) is a fumaric acid ester approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). In both the brain and periphery, DMF and its metabolite monomethyl fumarate (MMF) exert anti-inflammatory and antioxidant effects. Our aim was to compare the effects of DMF and MMF on inflammatory and antioxidant pathways within astrocytes, a critical supporting glial cell in the central nervous system (CNS).

miRNAs As Emerging Regulators of Oligodendrocyte Development and Differentiation.

Chronic demyelination is a hallmark of neurological disorders such as multiple sclerosis (MS) and several leukodystrophies. In the central nervous system (CNS), remyelination is a regenerative process that is often inadequate during these pathological states. In the MS context, in situ evidence suggests that remyelination is mediated by populations of oligodendrocyte progenitor cells (OPCs) that proliferate, migrate, and differentiate into mature, myelin-producing oligodendrocytes at sites of demyelinated lesions.