title: Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis.
abstract: Oligodendrocytes are well known targets for immune-mediated and infectious diseases, and have been suggested to play a role in neurodegeneration. Here, we report the involvement of oligodendrocytes and their progenitor cells in the ventral grey matter of the spinal cord in amyotrophic lateral sclerosis, a neurodegenerative disease of motor neurons. Degenerative changes in oligodendrocytes were abundantly present in human patients with amyotrophic lateral sclerosis and in an amyotrophic lateral sclerosis mouse model. In the mouse model, morphological changes in grey matter oligodendrocytes became apparent before disease onset, increasingly so during disease progression, and oligodendrocytes ultimately died. This loss was compensated by increased proliferation and differentiation of oligodendrocyte precursor cells. However, these newly differentiated oligodendrocytes were dysfunctional as suggested by their reduced myelin basic protein and monocarboxylate transporter 1 expression. Mutant superoxide dismutase 1 was found to directly affect monocarboxylate transporter 1 protein expression. Our data suggest that oligodendroglial dysfunction may be a contributor to motor neuron degeneration in amyotrophic lateral sclerosis.
authors: Laboratory of Neurobiology, Vesalius Research Centre, VIB, 3000 Leuven, Belgium.
authors: Thomas
authors: T
authors: Philips
authors: Andre
authors: A
authors: Bento-Abreu
authors: Annelies
authors: A
authors: Nonneman
authors: Wanda
authors: W
authors: Haeck
authors: Kim
authors: K
authors: Staats
authors: Veerle
authors: V
authors: Geelen
authors: Nicole
authors: N
authors: Hersmus
authors: Benno
authors: B
authors: Küsters
authors: Ludo
authors: L
authors: Van Den Bosch
authors: Philip
authors: P
authors: Van Damme
authors: William D
authors: WD
authors: Richardson
authors: Wim
authors: W
authors: Robberecht
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009836:Oligodendroglia / Q000201:enzymology / Q000473:pathology*; D013482:Superoxide Dismutase / Q000235:genetics
chemical_list: C109415:SOD1 G93A protein; D013482:Superoxide Dismutase
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