Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism.

Autor: Kotah JM; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Kater MSJ; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Brosens N; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Lesuis SL; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Tandari R; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Blok TM; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Marchetto L; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Yusaf E; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Koopmans FTW; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Smit AB; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Lucassen PJ; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Krugers HJ; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands., Verheijen MHG; Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Korosi A; Brain Plasticity Group, Swammerdam Institute for Life Sciences - Center for Neuroscience, University of Amsterdam, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2024 Mar; Vol. 20 (3), pp. 1637-1655. Date of Electronic Publication: 2023 Dec 06.
DOI: 10.1002/alz.13569
Abstrakt: Introduction: Early-life stress (ES) increases the risk for Alzheimer's disease (AD). We and others have shown that ES aggravates amyloid-beta (Aβ) pathology and promotes cognitive dysfunction in APP/PS1 mice, but underlying mechanisms remain unclear.
Methods: We studied how ES affects the hippocampal synaptic proteome in wild-type (WT) and APP/PS1 mice at early and late pathological stages, and validated hits using electron microscopy and immunofluorescence.
Results: The hippocampal synaptosomes of both ES-exposed WT and early-stage APP/PS1 mice showed a relative decrease in actin dynamics-related proteins and a relative increase in mitochondrial proteins. ES had minimal effects on older WT mice, while strongly affecting the synaptic proteome of advanced stage APP/PS1 mice, particularly the expression of astrocytic and mitochondrial proteins.
Discussion: Our data show that ES and amyloidosis share pathogenic pathways involving synaptic mitochondrial dysfunction and lipid metabolism, which may underlie the observed impact of ES on the trajectory of AD.
(© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze: MEDLINE
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