title: Oligodendroglia in cortical multiple sclerosis lesions decrease with disease progression, but regenerate after repeated experimental demyelination.
abstract: Cerebral cortex shows a high endogenous propensity for remyelination. Yet, widespread subpial cortical demyelination (SCD) is a common feature in progressive multiple sclerosis (MS) and can already be found in early MS. In the present study, we compared oligodendroglial loss in SCD in early and chronic MS. Furthermore, we addressed in an experimental model whether repeated episodes of inflammatory SCD could alter oligodendroglial repopulation and subsequently lead to persistently demyelinated cortical lesions. NogoA(+) mature oligodendrocytes and Olig2(+) oligodendrocyte precursor cells were examined in SCD in patients with early and chronic MS, normal-appearing MS cortex, and control cortex as well as in the rat model of repeated targeted cortical experimental autoimmune encephalomyelitis (EAE). NogoA(+) and Olig2(+) cells were significantly reduced in SCD in patients with chronic, but not early MS. Repeated induction of SCD in rats resulted only in a transient loss of NogoA(+), but not Olig2(+) cells during the demyelination phase. This phase was followed by complete oligodendroglial repopulation and remyelination, even after four episodes of demyelination. Our data indicate efficient oligodendroglial repopulation in subpial cortical lesions in rats after repeated SCD that was similar to early, but not chronic MS cases. Accordingly, four cycles of experimental de- and remyelination were not sufficient to induce sustained remyelination failure as found in chronic cortical MS lesions. This suggests that alternative mechanisms contribute to oligodendrocyte depletion in chronic cortical demyelination in MS.
authors.affiliation: Institute of Neuropathology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37099, Göttingen, Germany.
authors.forename: Enrique Garea
authors.initials: EG
authors.lastname: Rodriguez
authors.forename: Christiane
authors.initials: C
authors.lastname: Wegner
authors.forename: Mario
authors.initials: M
authors.lastname: Kreutzfeldt
authors.forename: Katharina
authors.initials: K
authors.lastname: Neid
authors.forename: Dietmar R
authors.initials: DR
authors.lastname: Thal
authors.forename: Tanja
authors.initials: T
authors.lastname: Jürgens
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Brück
authors.forename: Christine
authors.initials: C
authors.lastname: Stadelmann
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002452:Cell Count; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D002908:Chronic Disease; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology* / Q000503:physiopathology; D009185:Myelin Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000070798:Nogo Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000473:pathology* / Q000502:physiology; D011917:Rats, Inbred Lew
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000076104:Oligodendrocyte Transcription Factor 2; C405708:OLIG2 protein, human; C522729:Olig2 protein, rat; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat