title: Clasmatodendrosis and β-amyloidosis in aging hippocampus.
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 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.
authors.affiliation: *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.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Mercatelli
authors.affiliation: *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.
authors.forename: Daniele
authors.initials: D
authors.lastname: Lana
authors.affiliation: *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.
authors.forename: Monica
authors.initials: M
authors.lastname: Bucciantini
authors.affiliation: *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.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Giovannini
authors.affiliation: *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.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cerbai
authors.affiliation: *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.
authors.forename: Franco
authors.initials: F
authors.lastname: Quercioli
authors.affiliation: *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.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zecchi-Orlandini
authors.affiliation: *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.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delfino
authors.affiliation: *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.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Wenk
authors.affiliation: *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 daniele.nosi@unifi.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Nosi
mesh_terms: D000367:Age Factors; D000375:Aging; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology*; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; C546339:Rbfox3 protein, rat
keywords: cell–cell interactions; central nervous system; clearance mechanism