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Characteristic microglial features in patients with hereditary diffuse leukoencephalopathy with spheroids.

Abstract：

OBJECTIVE:To clarify the histopathological alterations of microglia in the brains of patients with hereditary diffuse leukoencephalopathy with spheroids (HDLS) caused by mutations of the gene encoding the colony stimulating factor-1 receptor (CSF-1R). METHODS:We examined 5 autopsied brains and 1 biopsy specimen from a total of 6 patients with CSF-1R mutations. Detailed immunohistochemical, biochemical, and ultrastructural features of microglia were examined, and quantitative analyses were performed. RESULTS:In layers 3 to 4 of the frontal cortex in HDLS brains, microglia showed relatively uniform and delicate morphology, with thin and winding processes accompanying knotlike structures, and significantly smaller areas of Iba1 immunoreactivity and lower numbers of Iba1-positive cells were evident in comparison with control brains. On the other hand, in layers 5 to 6 and the underlying white matter, microglia were distributed unevenly; that is, in some areas they had accumulated densely, whereas in others they were scattered. Immunoblot analyses of microglia-associated proteins, including CD11b and DAP12, revealed that HDLS brains had significantly lower amounts of these proteins than diseased controls, although Ki-67-positive proliferative microglia were not reduced. Ultrastructurally, the microglial cytoplasm and processes in HDLS showed vesiculation of the rough endoplasmic reticulum and disaggregated polyribosomes, indicating depression of protein synthesis. On the other hand, macrophages were immunonegative for GLUT-5 or P2ry12, indicating that they were derived from bone marrow. INTERPRETATION:The pathogenesis of HDLS seems to be associated with microglial vulnerability and morphological alterations. Ann Neurol 2016;80:554-565.

journal_name

Ann Neurol

journal_title

Annals of neurology

authors

Tada M,Konno T,Tada M,Tezuka T,Miura T,Mezaki N,Okazaki K,Arakawa M,Itoh K,Yamamoto T,Yokoo H,Yoshikura N,Ishihara K,Horie M,Takebayashi H,Toyoshima Y,Naito M,Onodera O,Nishizawa M,Takahashi H,Ikeuchi T,Kakita A

doi

10.1002/ana.24754

subject

Has Abstract

pub_date

2016-10-01 00:00:00

pages

554-65

issue

eissn

0364-5134

issn

1531-8249

journal_volume

pub_type

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Characteristic microglial features in patients with hereditary diffuse leukoencephalopathy with spheroids.