In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 8 ( 2022-8-12), p. e1010747-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010747
DOI:
10.1371/journal.ppat.1010747.g001
DOI:
10.1371/journal.ppat.1010747.g002
DOI:
10.1371/journal.ppat.1010747.g003
DOI:
10.1371/journal.ppat.1010747.g004
DOI:
10.1371/journal.ppat.1010747.g005
DOI:
10.1371/journal.ppat.1010747.g006
DOI:
10.1371/journal.ppat.1010747.s001
DOI:
10.1371/journal.ppat.1010747.s002
DOI:
10.1371/journal.ppat.1010747.s003
DOI:
10.1371/journal.ppat.1010747.s004
DOI:
10.1371/journal.ppat.1010747.s005
DOI:
10.1371/journal.ppat.1010747.s006
DOI:
10.1371/journal.ppat.1010747.s007
DOI:
10.1371/journal.ppat.1010747.s008
DOI:
10.1371/journal.ppat.1010747.s009
DOI:
10.1371/journal.ppat.1010747.s010
DOI:
10.1371/journal.ppat.1010747.s011
DOI:
10.1371/journal.ppat.1010747.s012
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2022
ZDB Id:
2205412-1