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Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

Acta neuropathologica, 2013-04, Vol.125 (4), p.595-608 [Peer Reviewed Journal]

The Author(s) 2013 ;COPYRIGHT 2013 Springer ;Springer-Verlag Berlin Heidelberg 2013 ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-013-1082-0 ;PMID: 23354834

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Title:
Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
Author: Singh, Shailender ; Metz, Imke ; Amor, Sandra ; van der Valk, Paul ; Stadelmann, Christine ; Brück, Wolfgang
Subjects: Adult ; Aged ; Amyloid beta-protein ; Amyloid beta-Protein Precursor - metabolism ; Autoimmunity ; Axons - metabolism ; Axons - pathology ; Brain - metabolism ; Brain - pathology ; Female ; HLA-DR Antigens - metabolism ; Humans ; Inflammation ; Male ; Medicine ; Medicine & Public Health ; Microglia - metabolism ; Microglia - pathology ; Middle Aged ; Multiple sclerosis ; Multiple Sclerosis - metabolism ; Multiple Sclerosis - pathology ; Nerve Fibers, Myelinated - metabolism ; Nerve Fibers, Myelinated - pathology ; Neuropeptide Y ; Neurosciences ; Original Paper ; Pathology ; Receptors, Neuropeptide Y - metabolism ; Wallerian Degeneration - metabolism ; Wallerian Degeneration - pathology
Is Part Of: Acta neuropathologica, 2013-04, Vol.125 (4), p.595-608
Description: Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesions. Although the etiology of MS is still not known, inflammation and autoimmunity are considered to be the central components of this disease. Previous studies provide evidence that Wallerian degeneration, occurring as a consequence of structural damage in MS lesions, might be responsible for observed pathological abnormalities in connected normal-appearing white matter. As innate immune cells, microglia/macrophages are the first to react to even minor pathological changes in the CNS. Biopsy tissue from 27 MS patients and autopsy and biopsy tissue from 22 normal and pathological controls were analyzed to determine the incidence of microglial nodules. We assessed MS periplaque white matter tissue from early disease stages to determine whether microglial nodules are associated with altered axons. With immunohistochemical methods, the spatial relation of the two phenomena was visualized using HLA-DR antibody for MHC II expression by activated microglia/macrophages and by applying antibodies against damaged axons, i.e., SMI32 (non-phosphorylated neurofilaments) and amyloid precursor protein as well as neuropeptide Y receptor Y1, which marks axons undergoing Wallerian degeneration. Our data demonstrate that the occurrence of microglial nodules is not specific to MS and is associated with degenerating as well as damaged axons in early MS. In addition, we show that early MS microglial nodules exhibit both pro- and antiinflammatory phenotypes.
Publisher: Berlin/Heidelberg: Springer-Verlag
Language: English
Identifier: ISSN: 0001-6322
EISSN: 1432-0533
DOI: 10.1007/s00401-013-1082-0
PMID: 23354834
Source: ProQuest One Psychology
MEDLINE
Alma/SFX Local Collection
Springer Nature OA/Free Journals
ProQuest Central

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Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

The Author(s) 2013 ;COPYRIGHT 2013 Springer ;Springer-Verlag Berlin Heidelberg 2013 ;ISSN: 0001-6322 ;EISSN: 1432-0533 ;DOI: 10.1007/s00401-013-1082-0 ;PMID: 23354834

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