Clasmatodendrosis and beta-amyloidosis in aging hippocampus

Anno: 2016

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

Affiliazione autori: Univ Florence, Dept Chem Ugo Schiff, Florence, Italy; Univ Florence, Dept Hlth Sci, Florence, Italy; Univ Florence, Dept Biomed Expt & Clin Sci Mario Serio, Florence, Italy; Univ Florence, Dept Expt & Clin Med, Florence, Italy; Univ Florence, Dept Biol, Florence, Italy; Natl Res Council CNR, Natl Inst Opt, Florence, Italy; Ohio State Univ, Dept Psychol, Columbus, OH USA.

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 beta-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 (-45% 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 A beta-mediated adhesions between neurons. These data define the effects of Ab 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 beta-amyloidosis in aging hippocampus. FASEB J. 30, 1480-1491 (2016). www.fasebj.org

Giornale/Rivista: FASEB JOURNAL

Volume: 30 (4)      Da Pagina: 1480  A: 1491

Maggiori informazioni: 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.
Parole chiavi: 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

Citazioni: 18
dati da “WEB OF SCIENCE” (of Thomson Reuters) aggiornati al: 2025-06-08
Riferimenti tratti da Isi Web of Knowledge: (solo abbonati)
Link per visualizzare la scheda su IsiWeb: Clicca qui
Link per visualizzare la citazioni su IsiWeb: Clicca qui