Axonal mitochondria adjust in size depending on g-ratio of surrounding myelin during homeostasis and advanced remyelination.

Demyelinating pathology is common in many neurological diseases such as multiple sclerosis, stroke, and Alzheimer's disease and results in axonal energy deficiency, dysfunctional axonal propagation, and neurodegeneration. During myelin repair and also during myelin homeostasis, mutual regulative processes between axons and myelin sheaths are known to be essential. However, proficient tools are lacking to characterize axon-myelin interdependence during (re)myelination.

Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis.

Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4α (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS.

Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity.

High-grade gliomas (HGGs) are the most aggressive and invasive primary brain tumors. The platelet-derived growth factor (PDGF) signaling pathway drives HGG progression, and enhanced expression of PDGF receptors (PDGFRs) is a well-established aberration in a subset of glioblastomas (GBMs). PDGFRA is expressed in glioma cells, whereas PDGFRB is mostly restricted to the glioma-associated stroma.

Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling.

The cytokine transforming growth factor-β (TGF-β) regulates the development and homeostasis of several tissue-resident macrophage populations, including microglia. TGF-β is not critical for microglia survival but is required for the maintenance of the microglia-specific homeostatic gene signature. Under defined host conditions, circulating monocytes can compete for the microglial niche and give rise to long-lived monocyte-derived macrophages residing in the central nervous system (CNS).

Usability of human Infinium MethylationEPIC BeadChip for mouse DNA methylation studies.

Background: The advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input. Whereas the use of Infinium Human Methylation BeadChips has shown great utility in clinical studies, no equivalent tool is available for rodent animal samples. We examined the feasibility of using the new Infinium MethylationEPIC BeadChip for studying DNA methylation in mouse.

Anti-inflammatory (M2) macrophage media reduce transmission of oligomeric amyloid beta in differentiated SH-SY5Y cells.

Neuroinflammation plays an influential role in Alzheimer's disease (AD), although the mechanisms underlying this phenomenon remain largely unknown. Microglia are thought to be responsible for the majority of these effects and can be characterized into resting (M0), proinflammatory (M1), or anti-inflammatory (M2) functional phenotypes. We investigated the effects of conditioned macrophage media, as an analogue to microglia, on the transfer of oligomeric amyloid beta (oAβ) between differentiated SH-SY5Y cells.

BAFF-secreting neutrophils drive plasma cell responses during emergency granulopoiesis.

Prolonged infections or adjuvant usage can trigger emergency granulopoiesis (EG), leading to dysregulation in neutrophil blood counts. However, the impact of EG on T and B cell function remains largely unknown. In this study, to address this question, we used a mouse model of neutropenia and studied immune activation after adjuvant administration.

Meta-analysis of association between Helicobacter pylori infection and multiple sclerosis.

Despite recent research focus on the association between Helicobacter pylori (H. pylori) infection and multiple sclerosis (MS) there is no consensus about the findings. To obtain a more comprehensive estimate of the association we conducted a meta-analysis to determine the prevalence of H.

Novel mechanism of macrophage-mediated metastasis revealed in a zebrafish model of tumor development.

Cancer metastasis can occur at early stages of tumor development due to facilitative alterations in the tumor microenvironment. Although imaging techniques have considerably improved our understanding of metastasis, early events remain challenging to study due to the small numbers of malignant cells involved that are often undetectable. Using a novel zebrafish model to investigate this process, we discovered that tumor-associated macrophages (TAM) acted to facilitate metastasis by binding tumor cells and mediating their intravasation.

Sweet and sour--oxidative and carbonyl stress in neurological disorders.

The nervous system is a unique network of different cell types and comprises a variety of proteins, lipids, and carbohydrates that have an important interplay with all major organs in the body. Homeostatic regulation of nervous tissue turnover must be carefully controlled, taking into account interactions of the nervous, endocrine, and immune systems. Clinical conditions affecting the nervous system range from mild cognitive perturbations such as headache, to life-threatening acute courses such as meningitis and glioblastoma, and to chronic neurodegenerative diseases such as multiple sclerosis.

Alternative splicing and transcriptome profiling of experimental autoimmune encephalomyelitis using genome-wide exon arrays.

Background: Multiple Sclerosis (MS) is a chronic inflammatory disease causing demyelination and nerve loss in the central nervous system. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that is widely used to investigate complex pathogenic mechanisms. Transcriptional control through isoform selection and mRNA levels determines pathway activation and ultimately susceptibility to disease.