Clasmatodendrosis and beta-amyloidosis in aging hippocampus

Year: 2016

Authors: Mercatelli R., Lana D., Bucciantini M., Giovannini M.G., Cerbai F., Quercioli F., Zecchi-Orlandini S., Delfino G., Wenk G.L., Nosi D.

Autors Affiliation: Department of Chemistry Ugo Schiff, University of Florence, Florence, Italy; Department of Health Sciences, University of Florence, Florence, Italy; Department of Biomedical Experimental and Clinical Sciences Mario Serio, University of Florence, Florence, Italy; Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy; Department of Biology, University of Florence, Florence, Italy; National Institute of Optics, National Research Council (CNR), Florence, Italy; Department of Psychology, Ohio State University, Columbus, OH, United States

Abstract: 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 inflammationrelated processes, such as b-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 confocalmicroscopy, implemented with a novel method to separate spectrally overlapped immunofluorescence and Ab 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 Ab aggregation (+300 and +800% of aggregated Ab 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 Ab clearance (245% of Ab deposits on APJs, and +33% of Ab deposits on neurons in old vs. chronically inflamed rats). Furthermore, APJ fragments colocalize with Ab deposits and are involved in novel Ab-mediated adhesions between neurons. These data define the effects of Ab deposition on astrocyte/neuron interactions as a key topic in AD biology.

Journal/Review: FASEB JOURNAL

Volume: 30 (4)      Pages from: 1480  to: 1491

More Information: The authors are grateful to Prof. Enrico Gratton (University of California, Irvine, Irvine, CA, USA) for his assistance on FLIM/phasor analyses, to Prof. Diego Minciacchi (University of Florence) for his help in the revision of the manuscript, and to Ente Cassa di Risparmio di Firenze for the granted funding.
KeyWords: Wistar rat, Age Factors; Aging; Amyloid beta-Peptides; Amyloidosis; Animals; Antigens, Nuclear; Astrocytes; CA1 Region, Hippocampal; Glial Fibrillary Acidic Protein; Male; Microscopy, Confocal; Microscopy, Fluorescence; Nerve Tissue Proteins; Rats, Wistar
DOI: 10.1096/fj.15-275503

Citations: 16
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