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Clasmatodendrosis and β‐amyloidosis in aging hippocampus
Author(s) -
Mercatelli Raffaella,
Lana Daniele,
Bucciantini Monica,
Giovannini Maria Grazia,
Cerbai Francesca,
Quercioli Franco,
ZecchiOrlandini Sandra,
Delfino Giovanni,
Wenk Gary L.,
Nosi Daniele
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-275503
Subject(s) - astrocyte , neuroscience , colocalization , hippocampus , neuron , amyloidosis , biology , pathology , alzheimer's disease , medicine , disease , central nervous system
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 (Ab) 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 old vs. control rats, respectively) and fragmentation (clasmatodendrosis) of astrocyte projections (APJs) (+250 and +1300% of APJ fragments in chronically inflamed and old vs. control rats, respectively). Clasmatodendrosis, in aged rats, associates with impairment of astrocyte‐mediated Aβ clearance (245% of Aβ deposits on APJs, and +33% of Aβ deposits on neurons in old vs. 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. FASEB J. 30, 1480–1491 (2016). www.fasebj.org