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@ARTICLE{Kaczmarczyk:165105,
author = {Kaczmarczyk, Lech and Schleif, Melvin and Dittrich, Lars
and Williams, Rhiannan H and Koderman, Maruša and Bansal,
Vikas and Rajput, Ashish and Schulte, Theresa and Jonson,
Maria and Krost, Clemens and Testaquadra, Fabio J and Bonn,
Stefan and Jackson, Walker Scot},
title = {{D}istinct translatome changes in specific neural
populations precede electroencephalographic changes in
prion-infected mice.},
journal = {PLoS pathogens},
volume = {18},
number = {8},
issn = {1553-7366},
address = {Lawrence, Kan.},
publisher = {PLoS},
reportid = {DZNE-2022-01414},
pages = {e1010747},
year = {2022},
note = {CC BY: https://creativecommons.org/licenses/by/4.0/},
abstract = {Selective vulnerability is an enigmatic feature of
neurodegenerative diseases (NDs), whereby a widely expressed
protein causes lesions in specific cell types and brain
regions. Using the RiboTag method in mice, translational
responses of five neural subtypes to acquired prion disease
(PrD) were measured. Pre-onset and disease onset timepoints
were chosen based on longitudinal electroencephalography
(EEG) that revealed a gradual increase in theta power
between 10- and 18-weeks after prion injection, resembling a
clinical feature of human PrD. At disease onset, marked by
significantly increased theta power and histopathological
lesions, mice had pronounced translatome changes in all five
cell types despite appearing normal. Remarkably, at a
pre-onset stage, prior to EEG and neuropathological changes,
we found that 1) translatomes of astrocytes indicated
reduced synthesis of ribosomal and mitochondrial components,
2) glutamatergic neurons showed increased expression of
cytoskeletal genes, and 3) GABAergic neurons revealed
reduced expression of circadian rhythm genes. These data
demonstrate that early translatome responses to
neurodegeneration emerge prior to conventional markers of
disease and are cell type-specific. Therapeutic strategies
may need to target multiple pathways in specific populations
of cells, early in disease.},
keywords = {Animals / Brain: pathology / Electroencephalography /
Humans / Mice / Neurons: metabolism / Prion Diseases:
pathology / Prions: metabolism / Prions (NLM Chemicals)},
cin = {AG Jackson / AG Heutink 1 / AG Petzold},
ddc = {610},
cid = {I:(DE-2719)1013019 / I:(DE-2719)1210002 /
I:(DE-2719)1013020},
pnm = {353 - Clinical and Health Care Research (POF4-353) / 354 -
Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-354},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35960762},
pmc = {pmc:PMC9401167},
doi = {10.1371/journal.ppat.1010747},
url = {https://pub.dzne.de/record/165105},
}