Increasing in situ nick end labeling of oligodendrocytes in white matter of patients with Binswanger's disease.
Increasing evidence suggests the presence of apoptotic cell death in many neurodegenerative diseases. However, in Binswanger's disease (BD), no information is available concerning the apoptosis-related pathologic changes that may occur in the white matter. To investigate whether apoptotic cell death is included in the pathophysiology of the white matter changes in BD, autopsied brains from patients with BD (n = 5) were compared with those of non-neurologic controls (n = 5). Terminal deoxynucleotidyl transferase-mediated dUTP in situ nick end labeling (TUNEL) was used as a marker for cell damage with DNA fragmentation. A proteolipid protein (PLP) messenger RNA (mRNA) hybridization signal was also used as a sensitive and specific marker of oligodendrocytes as well as glial fibrillary acidic protein (GFAP) immunoreactivity as a marker of astrocytes. There were frequent TUNEL-positive cells in the rarefied white matter of patients with BD. TUNEL-positive cells were found 15-fold more numerously in BD than in controls (P < .01). TUNEL-positive cells were presumably oligodendrocytes because of their coexpression with PLP mRNA. The numbers of GFAP-positive astrocytes were significantly decreased in BD compared with those in control subjects. The reduction in numbers of PLP mRNA-positive oligodendrocytes were also seen in BD, but these changes did not reach the level of significance. The pathologic alterations in BD brains include increased TUNEL-positive oligodendrocytes, associated with degradation of myelin. Although TUNEL-positive glial cells did not show typical apoptotic morphologic features, these findings suggest that increase in in situ nick end labeling of oligodendrocytes in white matter may play an important role in the pathophysiology of BD.
Masumura
M
M
Brain Function Research Institute, c/o National Cardiovascular Center, Suita, Osaka, Japan.
Hata
R
R
Akatsu
H
H
Kosaka
K
K
Yamamoto
T
T
Nagai
Y
Y
Sawada
T
T