Accumulation of beta-amyloid in the brain microvessels accompanies increased hyperphosphorylated tau proteins following microsphere embolism in aged rats

F. Han, A. Ali Raie, N. Shioda, Z. H. Qin, K. Fukunaga

研究成果: Article査読

26 被引用数 (Scopus)

抄録

To define mechanisms underlying neurovascular injury following brain embolism-induced neurodegeneration, we investigated temporal and spatial pathological changes in brain microvessels up to 12 weeks after microsphere embolism (ME) induction in aged male rats. Mild ME upregulated endothelial nitric oxide synthase (eNOS) and protein tyrosine nitration in brain microvessels. Strong β-amyloid immunoreactivity coincident with increased eNOS immunoreactivity was observed in microvessels. Immunoblotting of purified brain microvessels revealed that β-amyloid accumulation significantly increased 1 week after ME induction and remained elevated for 12 weeks. Importantly, β-amyloid accumulation in brain parenchyma was also observed in areas surrounding injured microvessels at 12 weeks. Levels of Alzheimer's-related hyperphosphorylated tau proteins also concomitantly increased in neurons surrounding regions of β-amyloid accumulation 12 weeks after ME induction, as did glycogen synthase kinase (GSK3β) (Tyr-216) phosphorylation. Taken together, ME-induced aberrant eNOS expression and subsequent protein tyrosine nitration in microvessels preceded β-amyloid accumulation both in microvessels and brain parenchyma, leading to hyperphosphorylation of neuronal tau proteins through GSK3β activation.

本文言語English
ページ(範囲)414-427
ページ数14
ジャーナルNeuroscience
153
2
DOI
出版ステータスPublished - 2008 5月 2
外部発表はい

ASJC Scopus subject areas

  • 神経科学(全般)

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