title: Oligodendroglial response in the spinal cord in TDP-43 proteinopathy with motor neuron involvement.
abstract: BACKGROUND
  TDP-43 proteinopathies represent a spectrum of neurodegenerative disorders. Variable clinical presentations including frontotemporal dementia, amyotrophic lateral sclerosis (ALS) and mixed forms are associated with the spatial heterogeneity of the TDP-43 pathology. Recent studies have emphasized the role of oligodendrocytes in the pathogenesis of ALS.
  
  
  OBJECTIVE
  To evaluate whether TDP-43 proteinopathies are associated with an oligodendroglial response.
  
  
  METHODS
  We performed a study on 7 controls and 10 diseased patients with spinal cord involvement. Using the oligodendroglia-specific antibody TPPP/p25, we assessed oligodendrocyte density in the lateral corticospinal tracts (LCSs) along with the presence of perineuronal oligodendrocytes (PNOGs) in the anterior horns. We performed a densitometry of myelin basic protein (MBP) immunoreactivity. The numbers of TDP-43 and p62 immunoreactive inclusions were counted in both the LCSs and the anterior horns.
  
  
  RESULTS
  Double immunolabeling confirmed that oligodendrocytes harbor TDP-43 inclusions. In the LCSs, MBP density, but not the number of oligodendrocytes, was decreased in the diseased group. However, oligodendrocyte counts in the LCS correlated positively, and the density of MBP inversely, with the number of neuronal inclusions in the anterior horn, suggestive of a compensatory response of oligodendrocytes. The number of neurons with PNOGs correlated with the amount of inclusions.
  
  
  CONCLUSIONS
  Our study further emphasizes the importance of oligodendroglia in the pathogenesis of TDP-43 proteinopathies with spinal cord involvement.
authors.affiliation: Department of Pathology and Molecular Medicine, Thomayer Hospital, Charles University in Prague, Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Rohan
authors.forename: Radoslav
authors.initials: R
authors.lastname: Matej
authors.forename: Robert
authors.initials: R
authors.lastname: Rusina
authors.forename: Gabor G
authors.initials: GG
authors.lastname: Kovacs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000870:Anterior Horn Cells / Q000378:metabolism / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism / Q000473:pathology*; D011712:Pyramidal Tracts / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology*; D057177:TDP-43 Proteinopathies / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; C499048:MBP protein, human; D004676:Myelin Basic Protein; C118585:P62 protein, human; D016601:RNA-Binding Proteins; C000598624:TARDBP protein, human