Clasmatodendrosis and b-amyloidosis in aging hippocampus
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, WistarDOI: 10.1096/fj.15-275503Citations: 6data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2020-10-18References taken from IsiWeb of Knowledge: (subscribers only)Connecting to view paper tab on IsiWeb: Click hereConnecting to view citations from IsiWeb: Click here