Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Daniele Lana
ORCID logo ,
Jacopo Junio Valerio Branca
ORCID logo ,
Giovanni Delfino
,
Maria Grazia Giovannini
ORCID logo ,
Fiorella Casamenti
,
Pamela Nardiello
,
Monica Bucciantini
ORCID logo ,
Massimo Stefani
,
Petr Zach
,
Sandra Zecchi-Orlandini
,
Daniele Nosi
*
Version 1 : Received: 16 August 2023 / Approved: 16 August 2023 / Online: 17 August 2023 (09:37:09 CEST)

A peer-reviewed article of this Preprint also exists.

Lana, D.; Branca, J.J.V.; Delfino, G.; Giovannini, M.G.; Casamenti, F.; Nardiello, P.; Bucciantini, M.; Stefani, M.; Zach, P.; Zecchi-Orlandini, S.; Nosi, D. 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. Cells 2023, 12, 2258. Lana, D.; Branca, J.J.V.; Delfino, G.; Giovannini, M.G.; Casamenti, F.; Nardiello, P.; Bucciantini, M.; Stefani, M.; Zach, P.; Zecchi-Orlandini, S.; Nosi, D. 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. Cells 2023, 12, 2258.

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 peptide (Aβ) is a microenvironmental component increasingly growing in the CNS, imposing time-evolving challenges on resident cells. This study aimed at investigating 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 astroglia syncytium and promoted a senile phenotype of reactive microglia, hindering Aβ clearance. In the late stages of 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.

Keywords

neuroinflammation; neurodegeneration; hippocampus; glial cells; cell-cell interactions; clasmatodendrosis; amyloid plaques; Aβ-aggregates; transgenic mouse; confocal microscopy

Subject

Biology and Life Sciences, Neuroscience and Neurology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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