The Biology of Oligodendrocytes

Half-title......Page 3
Title......Page 5
Copyright......Page 6
Dedication......Page 7
Contents......Page 9
Preface......Page 11
Contributors......Page 13
Neuroglia......Page 17
The third element – discovery of the oligodendrocyte......Page 18
Morphology of oligodendrocytes......Page 19
Organization of myelinated axons......Page 20
Non-compact myelin......Page 21
Evolution of myelination: myelin makes the world go around......Page 24
Oligodendrocyte involvement in psychiatric disorders......Page 25
Perturbation of oligodendrocyte function in transgenic models......Page 26
Myelin model of the human brain......Page 28
Classification of NG2+ cells......Page 29
NG2+ cells communicate with neurons......Page 30
NG2+ cells can spike......Page 31
Oligodendrocytes secrete soluble mediators......Page 32
Wrap up......Page 34
Introduction......Page 35
Origin and specification of oligodendrocytes......Page 36
Origin and specification of Schwann cells......Page 39
Function, migration, survival and differentiation of Schwann cell precursors......Page 41
Immature Schwann cells: sorting out of myelin-competent axons and switch to the myelination program......Page 43
Axonal control of myelination......Page 44
Cell contact in myelination......Page 47
Myelin-specific components of oligodendrocytes and Schwann cells......Page 49
The contribution of myelinating glial cells to the formation of nodal compartments......Page 50
The node of Ranvier proper......Page 51
Paranodes......Page 52
Juxtaparanodes......Page 53
Impact of oligodendrocytes......Page 54
The myelin-associated inhibitors Nogo, MAG and OMgp and their impact on axon regeneration......Page 55
Axon guidance molecules as oligodendrocyte-derived inhibitors of neurite growth......Page 58
Impact of Schwann cells......Page 59
Expression of Schwann-cell-related nerve growth-promoting molecules and lack of persistent nerve growth inhibitors foster axonal regrowth in the PNS......Page 60
Schwann-cell-related limitations in peripheral nerve regeneration: long-term denervation and pathway cues......Page 63
Introduction......Page 65
Oligodendrocyte precursors and stem cells......Page 66
Localized origins of oligodendrocyte precursors......Page 67
Extracellular cues controlling the initial appearance of OPCs......Page 69
Relationships between oligodendrocytes, astrocytes and neurons......Page 70
Transcriptional control of OPC induction......Page 71
Regulation of oligodendrocyte precursor proliferation and maturation......Page 73
Major mitogens for oligodendrocyte precursors......Page 74
Migration of oligodendrocyte precursors during development......Page 75
Intrinsic timers of oligodendrocyte differentiation......Page 77
The control of the onset of myelination......Page 78
Consequences for myelin repair......Page 79
Oligodendrocytes have a highly polarized shape......Page 80
Molecular composition of myelin and oligodendrocyte membranes......Page 85
Compact myelin and roles of the major myelin proteins......Page 86
Radial component of compact CNS myelin......Page 90
Non-compact myelin domains and axonal organization at the node......Page 91
The nodal region......Page 94
Paranodal loops......Page 95
Juxtaparanodal regions......Page 96
Adaxonal membrane and internodal axolemma......Page 97
The abaxonal membrane and outer tongue process......Page 99
Premyelinating oligodendrocytes have non-polarized membranes......Page 100
Establishment of a specialized microtubule network underlies oligodendrocyte polarization......Page 102
βIV tubulin expression......Page 103
Secretory pathway proteins are targeted to different oligodendrocyte membranes......Page 105
Unfolded protein response......Page 107
Myelin basic protein is localized via RNA translocation......Page 108
Spiral growth extends the oligodendrocyte plasma membrane around axons......Page 110
Reciprocal interactions between oligodendrocytes and axons regulate myelination and promote axonal survival......Page 112
Axonal signaling modulates myelin thickness......Page 113
Oligodendrocytes modulate axonal diameter and survival......Page 116
Summary and conclusions......Page 118
Oligodendrocyte specification......Page 119
Genomic approaches to oligodendrocyte biology......Page 120
Genetic diseases affecting oligodendrocytes......Page 122
Post-transcriptional regulation of myelination......Page 126
Prospectus......Page 129
Multiple sclerosis......Page 139
Progressive multifocal leukoencephalopathy (PML)......Page 141
Acute disseminated encephalomyelitis......Page 142
Neuromyelitis optica (NMO)......Page 143
Major histocompatibility complex (MHC)......Page 144
Cytokines......Page 145
Chemokines......Page 147
Clusters of differentiation (CD)......Page 149
Glutamate......Page 151
Corticosteroids and NF-kB......Page 152
Adhesion molecules......Page 153
Complement......Page 154
Oligodendrocytes as antigen-presenting cells......Page 155
Macrophages......Page 156
Lymphocytes......Page 157
Conclusion and perspectives......Page 159
Introduction......Page 161
Oligodendrocyte damage in disease: demyelination......Page 162
Repair of demyelination; oligodendrocyte regeneration......Page 163
What cells are responsible for spontaneous myelin repair?......Page 164
Why is spontaneous remyelination not more extensive?......Page 167
Therapeutic remyelination: could therapy with myelinating cells reverse MS?......Page 169
Axon damage and MS......Page 173
Stem cells and tissue repair in MS......Page 175
Introduction......Page 178
Oligodendrocyte pathology in injury......Page 182
Myelin sheath pathology in injury......Page 184
Response of oligodendrocyte progenitors to injury......Page 186
Remyelination after injury: how complete is it?......Page 189
Myelin pathology in injury and normal aging: many commonalities?......Page 191
Conclusion......Page 193
Oligodendroglial pathology in early and chronic MS lesions......Page 195
Apoptosis-related mechanisms......Page 198
Cell-mediated mechanisms......Page 199
Antibody-and complement-mediated mechanisms......Page 202
Histotoxic hypoxia......Page 203
Glutamate-mediated mechanisms......Page 204
Reactive oxygen species-and reactive nitrogen species-mediated mechanisms......Page 205
Remyelination in MS lesions......Page 206
Oligodendrocyte progenitor cells......Page 208
Summary......Page 209
Periventricular leukomalacia......Page 210
Hypoxic-ischemic injury and periventricular leukomalacia......Page 213
Excitotoxicity and PVL......Page 214
AMPA receptors expressed in oligodendrocytes: culture studies......Page 215
AMPA receptors expressed in oligodendrocytes: in vivo studies......Page 216
NMDA receptor expression in white matter......Page 217
Metabotropic glutamate receptor expression in white matter......Page 219
Glutamate transporters in white matter......Page 220
Glutamatergic signaling in oligodendrocyte development and myelination......Page 222
Summary......Page 224
References......Page 226
Index......Page 302