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In mammals, large caliber axons are ensheathed by myelin, a glial specialization supporting axon integrity and conferring accelerated and energy‐efficient action potential conduction. Myelin basic protein (MBP) is required for normal myelin elaboration with maximal mbp transcription in oligodendrocytes requiring the upstream M3 enhancer. To further characterize the mechanism regulating mbp transcription,...
Protein zero (P0) is the major structural component of peripheral myelin. Lack of this adhesion protein from Schwann cells causes a severe dysmyelinating neuropathy with secondary axonal degeneration in humans with the neuropathy Dejerine‐Sottas syndrome (DSS) and in the corresponding mouse model (P0null‐mice). In the mammalian CNS, the tetraspan‐membrane protein PLP is the major structural myelin...
Fyn, a member of the Src family of nonreceptor tyrosine kinases, promotes central nervous system myelination during development; however the mechanisms mediating this effect remain unknown. Here we show that Fyn phosphorylation is modulated by BDNF in vivo. Concordant with this, we find that BDNF stimulates Fyn phosphorylation in myelinating cocultures, an effect dependent on oligodendroglial expression...
Myelin is the multi‐layered membrane that surrounds most axons and is produced by oligodendrocytes in the central nervous system (CNS). In addition to its important role in enabling rapid nerve conduction, it has become clear in recent years that myelin plays additional vital roles in CNS function. Myelinating oligodendrocytes provide metabolic support to axons and active myelination is even involved...
Myelination in corpus callosum plays important role for normal brain functions by transferring neurological information between various brain regions. However, the factors controlling expression of myelin genes in myelination are poorly understood. Here, CXXC5, a recently identified protein with CXXC‐type zinc finger DNA binding motif, was characterized as a transcriptional activator of major myelin...
The Na+/Ca2+ exchanger NCX3, recently identified as a myelin membrane component, is involved in the regulation of [Ca2+]i during oligodendrocyte maturation. Here NCX3 involvement was studied in myelin oligodendrocyte glycoprotein (MOG)‐induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Western blotting and quantitative colocalization studies performed in...
White matter injury following ischemic stroke is a major cause of functional disability. Injury to both myelinated axons and oligodendrocytes, the myelin producing cells in the central nervous system, occurs in experimental models of ischemic stroke. Age‐related changes in white matter vulnerability to ischemia have been extensively studied and suggest that both the perinatal and the aged periods...
Multiple sclerosis is a chronic inflammatory, demyelinating degenerative disease of the central nervous system. Current treatments target pathological immune responses to counteract the inflammatory processes. However, these drugs do not restrain the long‐term progression of clinical disability. For this reason, new therapeutic approaches and identification of novel target molecules are needed to...
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