星形膠質(zhì)細(xì)胞控制健康人群和病患大腦的許多功能,，包括控制再生反應(yīng),。阿爾茨海默氏病的患者淀粉樣蛋白斑沉積，神經(jīng)元功能退化,，同時星形膠質(zhì)細(xì)胞變得異?；钴S。到現(xiàn)在為止,，許多研究人員認(rèn)為,，星形膠質(zhì)細(xì)胞的過度活動發(fā)揮負(fù)調(diào)控作用，促進(jìn)這種破壞性疾病阿爾茨海默氏癥的進(jìn)展,。
在這項(xiàng)新研究中,，美國和瑞典研究小組利用中，他們抑制阿爾茨海默氏癥轉(zhuǎn)基因老鼠模型中過度活躍的星形膠質(zhì)細(xì)胞,，結(jié)果發(fā)現(xiàn)與正常小鼠相比,，這些小鼠的淀粉樣蛋白沉積增多。
Milos Pekny教授說：現(xiàn)在,，研究人員需要了解過度活躍的星形膠質(zhì)細(xì)胞在阿爾茨海默氏癥疾病進(jìn)展中的機(jī)制,。在分子水平上了解這個過程應(yīng)該能幫助設(shè)計以星形膠質(zhì)細(xì)胞為靶標(biāo)的治療策略。
Jin-Moo Lee教授表示：阿爾茨海默氏病患者大腦中星形膠質(zhì)細(xì)胞的過度活躍與小膠質(zhì)細(xì)胞的活化緊密相連,，小膠質(zhì)細(xì)胞是大腦的自身免疫細(xì)胞,。這意味著，這兩種細(xì)胞的溝通共同調(diào)解疾病發(fā)展,。
這兩個國際神經(jīng)科學(xué)家合作團(tuán)隊(duì)正在進(jìn)一步研究以了解星形膠質(zhì)細(xì)胞的分子機(jī)制,，希望能防止阿爾茨海默氏癥中淀粉樣蛋白斑塊的沉積。（生物谷：Bioon.com）
doi:10.1096/fj.12-208660
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Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice
Andrew W. Kraft*, Xiaoyan Hu*, Hyejin Yoon*, Ping Yan*, Qingli Xiao*, Yan Wang*, et al.
The accumulation of aggregated amyloid-β (Aβ) in amyloid plaques is a neuropathological hallmark of Alzheimer's disease (AD). Reactive astrocytes are intimately associated with amyloid plaques; however, their role in AD pathogenesis is unclear. We deleted the genes encoding two intermediate filament proteins required for astrocyte activation—glial fibrillary acid protein (Gfap) and vimentin (Vim)—in transgenic mice expressing mutant human amyloid precursor protein and presenilin-1 (APP/PS1). The gene deletions increased amyloid plaque load: APP/PS1 Gfap?/?Vim?/? mice had twice the plaque load of APP/PS1 Gfap+/+Vim+/+ mice at 8 and 12 mo of age. APP expression and soluble and interstitial fluid Aβ levels were unchanged, suggesting that the deletions had no effect on APP processing or Aβ generation. Astrocyte morphology was markedly altered by the deletions: wild-type astrocytes had hypertrophied processes that surrounded and infiltrated plaques, whereas Gfap?/?Vim?/? astrocytes had little process hypertrophy and lacked contact with adjacent plaques. Moreover, Gfap and Vim gene deletion resulted in a marked increase in dystrophic neurites (2- to 3-fold higher than APP/PS1 Gfap+/+Vim+/+ mice), even after normalization for amyloid load. These results suggest that astrocyte activation limits plaque growth and attenuates plaque-related dystrophic neurites. These activities may require intimate contact between astrocyte and plaque.—Kraft, A. W., Hu, X., Yoon, H., Yan, P., Xiao, Q., Wang, Y., Gil, S. C., Brown, J., Wilhelmsson, U., Restivo, J. L., Cirrito, J. R., Holtzman, D. M., Kim, J., Pekny, M., Lee, J.-M. Attenuating astrocyte activation accelerates plaque pathogenesis in APP/PS1 mice.
