Unique signatures of stress-induced senescent human astrocytes
(2020) In Experimental Neurology 334.- Abstract
Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions. Senescent astrocytes were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet the difference between senescent and reactive astrocytes is unclear. We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities. In a cell culture model of human fetal astrocytes, we determined a unique senescent transcriptome distinct from reactive astrocytes, which comprises dysregulated pathways. Both, senescent and reactive human astrocytes activated a proinflammatory pattern. Astrocyte senescence was at... (More)
Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions. Senescent astrocytes were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet the difference between senescent and reactive astrocytes is unclear. We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities. In a cell culture model of human fetal astrocytes, we determined a unique senescent transcriptome distinct from reactive astrocytes, which comprises dysregulated pathways. Both, senescent and reactive human astrocytes activated a proinflammatory pattern. Astrocyte senescence was at least partially depending on active mechanistic-target-of-rapamycin (mTOR) and DNA-damage response signaling, both drivers of senescence. To further investigate how PD and senescence connect to each other, we asked if a PD-linked environmental factor induces senescence and if senescence impairs midbrain neurons. We could show that the PD-linked pesticide rotenone causes astrocyte senescence. We further delineate, that the senescent secretome exaggerates rotenone-induced neurodegeneration in midbrain neurons differentiated from human induced pluripotent stem cells (hiPSC) of PD patients with alpha-synuclein gene (SNCA) locus duplication.
(Less)
- author
- Simmnacher, Katrin ; Krach, Florian ; Schneider, Yanni ; Alecu, Julian E. ; Mautner, Lena ; Klein, Paulina ; Roybon, Laurent LU ; Prots, Iryna ; Xiang, Wei and Winner, Beate
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alpha synuclein, Astrocyte neuron interplay, iPSC derived neurons, Parkinson's disease, Reactive astrocyte, Rotenone, Senescence
- in
- Experimental Neurology
- volume
- 334
- article number
- 113466
- publisher
- Elsevier
- external identifiers
-
- scopus:85091624361
- pmid:32949572
- ISSN
- 0014-4886
- DOI
- 10.1016/j.expneurol.2020.113466
- language
- English
- LU publication?
- yes
- id
- e18636c8-a69e-4445-9ac1-f1687677f09d
- date added to LUP
- 2020-10-22 14:44:35
- date last changed
- 2024-05-30 23:40:04
@article{e18636c8-a69e-4445-9ac1-f1687677f09d,
abstract = {{<p>Senescence was recently linked to neurodegeneration and astrocytes are one of the major cell types to turn senescent under neurodegenerative conditions. Senescent astrocytes were detected in Parkinson's disease (PD) patients' brains besides reactive astrocytes, yet the difference between senescent and reactive astrocytes is unclear. We aimed to characterize senescent astrocytes in comparison to reactive astrocytes and investigate differences and similarities. In a cell culture model of human fetal astrocytes, we determined a unique senescent transcriptome distinct from reactive astrocytes, which comprises dysregulated pathways. Both, senescent and reactive human astrocytes activated a proinflammatory pattern. Astrocyte senescence was at least partially depending on active mechanistic-target-of-rapamycin (mTOR) and DNA-damage response signaling, both drivers of senescence. To further investigate how PD and senescence connect to each other, we asked if a PD-linked environmental factor induces senescence and if senescence impairs midbrain neurons. We could show that the PD-linked pesticide rotenone causes astrocyte senescence. We further delineate, that the senescent secretome exaggerates rotenone-induced neurodegeneration in midbrain neurons differentiated from human induced pluripotent stem cells (hiPSC) of PD patients with alpha-synuclein gene (SNCA) locus duplication.</p>}},
author = {{Simmnacher, Katrin and Krach, Florian and Schneider, Yanni and Alecu, Julian E. and Mautner, Lena and Klein, Paulina and Roybon, Laurent and Prots, Iryna and Xiang, Wei and Winner, Beate}},
issn = {{0014-4886}},
keywords = {{Alpha synuclein; Astrocyte neuron interplay; iPSC derived neurons; Parkinson's disease; Reactive astrocyte; Rotenone; Senescence}},
language = {{eng}},
publisher = {{Elsevier}},
series = {{Experimental Neurology}},
title = {{Unique signatures of stress-induced senescent human astrocytes}},
url = {{http://dx.doi.org/10.1016/j.expneurol.2020.113466}},
doi = {{10.1016/j.expneurol.2020.113466}},
volume = {{334}},
year = {{2020}},
}