Myelination, the process by which oligodendrocytes form the myelin sheath around axons, is key to axonal signal transduction and related motor function in the central nervous system (CNS). Aging is characterized by degenerative changes in the myelin sheath, although the molecular underpinnings of normal and aberrant myelination remain incompletely understood. Here we report that axon myelinatio...

Despite the biophysical and clinical importance of differentiating nodal and internodal axolemma, very little is known about the process. We chose to study myelination and node of Ranvier formation in the hypomyelinating mouse mutant claw paw (clp). The phenotype of clp is delayed myelination in the peripheral nervous system. The specific defect is unknown but is thought to arise from a breakdo...

Bilirubin-induced neurologic dysfunction (BIND) and kernicterus has been used to describe moderate to severe neurologic dysfunction observed in children exposed to excessive levels of total serum bilirubin (TSB) during the neonatal period. Here we use a new mouse model that targets deletion of the Ugt1 locus and the Ugt1a1 gene in liver to promote hyperbilirubinemiainduced seizures and central ...

In the gray matter of the brain, astrocytes have been suggested to export lactate (derived from glucose or glycogen) to neurons to power their mitochondria. In the white matter, lactate can support axon function in conditions of energy deprivation, but it is not known whether lactate acts by preserving energy levels in axons or in oligodendrocytes, the myelinating processes of which are damaged...

Wrapping of the myelin sheath around axons by oligodendrocytes is critical for the rapid conduction of electrical signals required for the normal functioning of the CNS. Myelination is a multistep process where oligodendrocytes progress through a well coordinated differentiation program regulated by multiple extracellular growth and differentiation signals. The intracellular transduction of the...

Low levels of survival of motor neuron (SMN) protein lead to spinal muscular atrophy (SMA). The major pathological hallmark of SMA is a loss of lower motor neurons from spinal cord and peripheral nerve. However, recent studies have revealed pathological changes in other cells and tissues of the neuromuscular system. Here, we demonstrate intrinsic, SMN-dependent defects in Schwann cells in SMA. ...

In this study, we show that oligodendrocyte differentiation is powerfully inhibited by activation of the Notch pathway. Oligodendrocytes and their precursors in the developing rat optic nerve express Notch1 receptors and, at the same time, retinal ganglion cells express Jagged1, a ligand of the Notch1 receptor, along their axons. Jagged1 expression is developmentally regulated, decreasing with ...

A specific antibody to myelin basic protein has been used to localize the protein in developing rat oligodendroglia and myelin. Basic protein is found in the oligodendroglial cytoplasm of anterior commissures of 5- and 7-day old rats before the beginning of myelination. Staining of basic protein in oligodendroglia increases, becoming most intense during early myelination; it decreases during ra...

Myelin is synthesized about the time of birth. The Src-family tyrosine kinase Fyn is involved in the initial events of myelination. Fyn is present in myelin-forming cells and is activated through stimulation of cell surface receptors such as large myelin-associated glycoprotein (L-MAG). Here we show that Fyn stimulates transcription of the myelin basic protein (MBP) gene for myelination. MBP is...

Previous transcriptome studies observed disrupted cellular processes in late-onset Alzheimer's disease (LOAD), yet it is unclear whether these changes are specific to LOAD, or are common to general neurodegeneration. In this study, we address this question by examining transcription in LOAD and comparing it to cognitively normal controls and a cohort of "disease controls." Differential transcri...