White matter integrity in mice requires continuous myelin synthesis at the inner tongue.

Myelin, the electrically insulating sheath on axons, undergoes dynamic changes over time. However, it is composed of proteins with long lifetimes. This raises the question how such a stable structure is renewed.

TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice.

The mechanisms regulating myelin repair in the adult central nervous system (CNS) are unclear. Here, we identify DNA hydroxymethylation, catalyzed by the Ten-Eleven-Translocation (TET) enzyme TET1, as necessary for myelin repair in young adults and defective in old mice. Constitutive and inducible oligodendrocyte lineage-specific ablation of Tet1 (but not of Tet2), recapitulate this age-related decline in repair of demyelinated lesions.

α-Synuclein in Plasma-Derived Extracellular Vesicles Is a Potential Biomarker of Parkinson's Disease.

Background: Extracellular vesicles are small vesicles that are released from many cells, including neurons. α-Synuclein has recently been described in extracellular vesicles derived from the central nervous system and may contribute to the spreading of disease pathology in α-synuclein-related neurodegeneration.

Objectives: We aimed to examine the potential diagnostic value of α-synuclein in plasma extracellular vesicles from patients with Parkinson's disease (PD).

Transmission Electron Microscopy of Oligodendrocytes and Myelin.

In this chapter, we describe protocols to study different aspects of oligodendrocytes and myelin using electron microscopy. First, we describe in detail how to prepare central nervous system tissue routinely by perfusion fixation of the animal and conventional embedding in Epon resin. Then, we explain how, with some modifications, chemically fixed tissue can be used for immunoelectron microscopy on cryosections.

Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity.

Glial support is critical for normal axon function and can become dysregulated in white matter (WM) disease. In humans, loss-of-function mutations of which encodes the inward-rectifying potassium channel KIR4.1, causes seizures and progressive neurological decline.

The MICOS component Mic60 displays a conserved membrane-bending activity that is necessary for normal cristae morphology.

The inner membrane (IM) of mitochondria displays an intricate, highly folded architecture and can be divided into two domains: the inner boundary membrane adjacent to the outer membrane and invaginations toward the matrix, called cristae. Both domains are connected by narrow, tubular membrane segments called cristae junctions (CJs). The formation and maintenance of CJs is of vital importance for the organization of the mitochondrial IM and for mitochondrial and cellular physiology.

A discoidin domain receptor 1 knock-out mouse as a novel model for osteoarthritis of the temporomandibular joint.

Discoidin domain receptor 1 (DDR-1)-deficient mice exhibited a high incidence of osteoarthritis (OA) in the temporomandibular joint (TMJ) as early as 9 weeks of age. They showed typical histological signs of OA, including surface fissures, loss of proteoglycans, chondrocyte cluster formation, collagen type I upregulation, and atypical collagen fibril arrangements. Chondrocytes isolated from the TMJs of DDR-1-deficient mice maintained their osteoarthritic characteristics when placed in culture.

Migratory chondrogenic progenitor cells from repair tissue during the later stages of human osteoarthritis.

The regeneration of diseased hyaline cartilage continues to be a great challenge, mainly because degeneration--caused either by major injury or by age-related processes--can overextend the tissue's self-renewal capacity. We show that repair tissue from human articular cartilage during the late stages of osteoarthritis harbors a unique progenitor cell population, termed chondrogenic progenitor cells (CPCs). These exhibit stem cell characteristics such as clonogenicity, multipotency, and migratory activity.

Nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis cartilage.

Objective: To investigate the presence and function of nidogen-1 and nidogen-2 in healthy human cartilage and in late-stage osteoarthritis (OA) cartilage.

Methods: The location and quantity of nidogen-1 and nidogen-2 protein and messenger RNA were determined in cartilage tissue obtained from healthy donors and from patients with late-stage knee OA. Samples were analyzed by immunohistochemistry, in situ hybridization, and real-time reverse transcription-polymerase chain reaction.