Early and progressive accumulation of reactive microglia in the Huntington disease brain

被引:395
作者
Sapp, E
Kegel, KB
Aronin, N
Hashikawa, T
Uchiyama, Y
Tohyama, K
Bhide, PG
Vonsattel, JP
DiFiglia, M
机构
[1] Massachusetts Gen Hosp, Lab Cellular Neurobiol, Dept Neurol, Charlestown, MA 02129 USA
[2] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA
[3] Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA USA
[4] RIKEN, Brain Sci Inst, Lab Neural Architecture, Wako, Saitama, Japan
[5] Osaka Univ, Sch Med, Dept Anat, Osaka, Japan
[6] Iwate Med Univ, Sch Med, Ctr Electron Microscopy & Bioimaging Res, Dept Neuroanat, Morioka, Iwate 020, Japan
关键词
human brain; huntingtin; Huntington disease; mutant huntingtin; nuclear inclusions; reactive microglia; thymosin beta 4;
D O I
10.1093/jnen/60.2.161
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Microglia may contribute to cell death in neurodegenerative diseases. We studied the activation of microglia in affected regions of Huntington disease (HD) brain by localizing thymosin beta -4 (T beta4), which is increased in reactive microglia. Activated microglia appeared in the neostriatum, cortex, and globus pallidus and the adjoining white matter of the HD brain, but not in control brain. In the striatum and cortex, reactive microglia occurred in all grades of pathology, accumulated with increasing grade, and grew in density in relation to degree of neuronal loss. The predominant morphology of activated microglia differed in the striatum and cortex. Processes of reactive microglia were conspicuous in low-grade HD, suggesting an early microglia response to changes in neuropil and axons and in the grade 2 and grade 3 cortex, were aligned with the apical dendrites of pyramidal neurons. Some reactive microglia contacted pyramidal neurons with huntingtin-positive nuclear inclusions. The early and proximate association of activated microglia with degenerating neurons in the HD brain implicates a role for activated microglia in HD pathogenesis.
引用
收藏
页码:161 / 172
页数:12
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