The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer’s disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM), and local cell–cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid β (Aβ) peptide is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed to investigate the temporal and spatial variations of the effects produced by this process on astrocytes and microglia, either directly or by interfering in their interactions. Ex vivo confocal analyses of hippocampal sections from the mouse model TgCRND8 at different ages have shown that overproduction of Aβ peptide induced early and time-persistent disassembly of functional astroglial syncytium and promoted a senile phenotype of reactive microglia, hindering Aβ clearance. In the late stages of the disease, these patterns were altered in the presence of Aβ-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding Aβ-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.

Morphofunctional Investigation in a Transgenic Mouse Model of Alzheimer’s Disease: Non-Reactive Astrocytes Are Involved in Aβ Load and Reactive Astrocytes in Plaque Build-Up / Lana, Daniele; Branca, Jacopo Junio Valerio; Delfino, Giovanni; Giovannini, Maria Grazia; Casamenti, Fiorella; Nardiello, Pamela; Bucciantini, Monica; Stefani, Massimo; Zach, Petr; Zecchi-Orlandini, Sandra; Nosi, Daniele. - In: CELLS. - ISSN 2073-4409. - ELETTRONICO. - 12:(2023), pp. 2258.0-2258.0. [10.3390/cells12182258]

Morphofunctional Investigation in a Transgenic Mouse Model of Alzheimer’s Disease: Non-Reactive Astrocytes Are Involved in Aβ Load and Reactive Astrocytes in Plaque Build-Up

Lana, Daniele;Branca, Jacopo Junio Valerio;Delfino, Giovanni;Giovannini, Maria Grazia;Casamenti, Fiorella;Nardiello, Pamela;Bucciantini, Monica;Stefani, Massimo;Zecchi-Orlandini, Sandra;Nosi, Daniele
2023

Abstract

The term neuroinflammation defines the reactions of astrocytes and microglia to alterations in homeostasis in the diseased central nervous system (CNS), the exacerbation of which contributes to the neurodegenerative effects of Alzheimer’s disease (AD). Local environmental conditions, such as the presence of proinflammatory molecules, mechanical properties of the extracellular matrix (ECM), and local cell–cell interactions, are determinants of glial cell phenotypes. In AD, the load of the cytotoxic/proinflammatory amyloid β (Aβ) peptide is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed to investigate the temporal and spatial variations of the effects produced by this process on astrocytes and microglia, either directly or by interfering in their interactions. Ex vivo confocal analyses of hippocampal sections from the mouse model TgCRND8 at different ages have shown that overproduction of Aβ peptide induced early and time-persistent disassembly of functional astroglial syncytium and promoted a senile phenotype of reactive microglia, hindering Aβ clearance. In the late stages of the disease, these patterns were altered in the presence of Aβ-plaques, surrounded by typically reactive astrocytes and microglia. Morphofunctional characterization of peri-plaque gliosis revealed a direct contribution of astrocytes in plaque buildup that might result in shielding Aβ-peptide cytotoxicity and, as a side effect, in exacerbating neuroinflammation.
2023
12
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Lana, Daniele; Branca, Jacopo Junio Valerio; Delfino, Giovanni; Giovannini, Maria Grazia; Casamenti, Fiorella; Nardiello, Pamela; Bucciantini, Monica; Stefani, Massimo; Zach, Petr; Zecchi-Orlandini, Sandra; Nosi, Daniele
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1329976
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