Mercatelli Raffaella, Lana Daniele, Bucciantini Monica, Giovannini Maria Grazia, Cerbai Francesca, Quercioli Franco, Zecchi-Orlandini Sandra, Delfino Giovanni, Wenk Gary L, Nosi Daniele
*Department of Chemistry "Ugo Schiff," Department of Health Sciences, Department of Biomedical Experimental and Clinical Sciences "Mario Serio," Department of Experimental and Clinical Medicine, and Department of Biology, University of Florence, Florence, Italy; National Institute of Optics, National Research Council (CNR), Florence, Italy; and Department of Psychology, The Ohio State University, Columbus, Ohio, USA.
*Department of Chemistry "Ugo Schiff," Department of Health Sciences, Department of Biomedical Experimental and Clinical Sciences "Mario Serio," Department of Experimental and Clinical Medicine, and Department of Biology, University of Florence, Florence, Italy; National Institute of Optics, National Research Council (CNR), Florence, Italy; and Department of Psychology, The Ohio State University, Columbus, Ohio, USA
FASEB J. 2016 Apr;30(4):1480-91. doi: 10.1096/fj.15-275503. Epub 2015 Dec 31.
Alterations of the tightly interwoven neuron/astrocyte interactions are frequent traits of aging, but also favor neurodegenerative diseases, such as Alzheimer disease (AD). These alterations reflect impairments of the innate responses to inflammation-related processes, such as β-amyloid (Aβ) burdening. Multidisciplinary studies, spanning from the tissue to the molecular level, are needed to assess how neuron/astrocyte interactions are influenced by aging. Our study addressed this requirement by joining fluorescence-lifetime imaging microscopy/phasor multiphoton analysis with confocal microscopy, implemented with a novel method to separate spectrally overlapped immunofluorescence and Aβ autofluorescence. By comparing data from young control rats, chronically inflamed rats, and old rats, we identified age-specific alterations of neuron/astrocyte interactions in the hippocampus. We found a correlation between Aβ aggregation (+300 and +800% of aggregated Aβ peptide in chronically inflamed and oldvs.control rats, respectively) and fragmentation (clasmatodendrosis) of astrocyte projections (APJs) (+250 and +1300% of APJ fragments in chronically inflamed and oldvs.control rats, respectively). Clasmatodendrosis, in aged rats, associates with impairment of astrocyte-mediated Aβ clearance (-45% of Aβ deposits on APJs, and +33% of Aβ deposits on neurons in oldvs.chronically inflamed rats). Furthermore, APJ fragments colocalize with Aβ deposits and are involved in novel Aβ-mediated adhesions between neurons. These data define the effects of Aβ deposition on astrocyte/neuron interactions as a key topic in AD biology.-Mercatelli, R., Lana, D., Bucciantini, M., Giovannini, M. G., Cerbai, F., Quercioli, F., Zecchi-Orlandini, S., Delfino, G., Wenk, G. L., Nos, D. Clasmatodendrosis and β-amyloidosis in aging hippocampus.
紧密交织的神经元/星形胶质细胞相互作用的改变是衰老的常见特征，但也有利于神经退行性疾病，如阿尔茨海默病（AD）。这些改变反映了对炎症相关过程的先天反应的损伤，如β-淀粉样蛋白（Aβ）负荷。需要从组织水平到分子水平的多学科研究来评估衰老如何影响神经元/星形胶质细胞的相互作用。我们的研究通过将荧光寿命成像显微镜/相量多光子分析与共聚焦显微镜相结合来满足这一要求，采用了一种新方法来分离光谱重叠的免疫荧光和Aβ自发荧光。通过比较年轻对照大鼠、慢性炎症大鼠和老年大鼠的数据，我们确定了海马体中神经元/星形胶质细胞相互作用的年龄特异性改变。我们发现Aβ聚集（慢性炎症大鼠和老年大鼠中聚集的Aβ肽分别比对照大鼠增加300%和800%）与星形胶质细胞突起（APJ）的碎片化（树突断裂）（慢性炎症大鼠和老年大鼠中APJ碎片分别比对照大鼠增加250%和1300%）之间存在相关性。在老年大鼠中，树突断裂与星形胶质细胞介导的Aβ清除受损有关（老年大鼠中APJ上的Aβ沉积物减少45%，神经元上的Aβ沉积物比慢性炎症大鼠增加33%）。此外，APJ碎片与Aβ沉积物共定位，并参与神经元之间新的Aβ介导的粘附。这些数据将Aβ沉积对星形胶质细胞/神经元相互作用的影响定义为AD生物学中的一个关键主题。-梅尔卡特利，R.，拉纳，D.，布奇安蒂尼，M.，乔瓦尼尼，M.G.，切尔巴伊，F.，奎尔乔利，F.，泽基-奥兰迪尼，S.，德尔菲诺，G.，温克，G.L.，诺斯，D.衰老海马体中的树突断裂和β-淀粉样变性。
