Clasmatodendrosis and β‐amyloidosis in aging hippocampus
Autor: | Daniele Nosi, Gary L. Wenk, Monica Bucciantini, Daniele Lana, Sandra Zecchi-Orlandini, Giovanni Delfino, Franco Quercioli, Maria Grazia Giovannini, Raffaella Mercatelli, Francesca Cerbai |
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Rok vydání: | 2015 |
Předmět: |
Male
0301 basic medicine Aging Pathology medicine.medical_specialty Central nervous system Hippocampus Nerve Tissue Proteins Biology Biochemistry 03 medical and health sciences 0302 clinical medicine Glial Fibrillary Acidic Protein Genetics medicine Animals Rats Wistar CA1 Region Hippocampal Molecular Biology Amyloid beta-Peptides Microscopy Confocal Glial fibrillary acidic protein Amyloidosis Age Factors Colocalization Antigens Nuclear medicine.disease 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence Astrocytes biology.protein Neuron Alzheimer's disease 030217 neurology & neurosurgery Biotechnology Astrocyte |
Zdroj: | The FASEB Journal. 30:1480-1491 |
ISSN: | 1530-6860 0892-6638 |
DOI: | 10.1096/fj.15-275503 |
Popis: | 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. |
Databáze: | OpenAIRE |
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