Journal Article

DZNE-2022-01414

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Distinct translatome changes in specific neural populations precede electroencephalographic changes in prion-infected mice.

Kaczmarczyk, L. (First author)DZNE* ; Schleif, M.DZNE* ; Dittrich, L.DZNE* ; Williams, R. H. ; Koderman, M. ; Bansal, V.DZNE* ; Rajput, A.Extern* ; Schulte, T.DZNE* ; Jonson, M. ; Krost, C.DZNE* ; Testaquadra, F. J.DZNE* ; Bonn, S.Extern* ; Jackson, W. S. (Last author)DZNE*

2022
PLoS Lawrence, Kan.

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Please use a persistent id in citations: doi:10.1371/journal.ppat.1010747

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.

Keyword(s): Animals (MeSH) ; Brain: pathology (MeSH) ; Electroencephalography (MeSH) ; Humans (MeSH) ; Mice (MeSH) ; Neurons: metabolism (MeSH) ; Prion Diseases: pathology (MeSH) ; Prions: metabolism (MeSH) ; Prions

Note: CC BY: https://creativecommons.org/licenses/by/4.0/

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Contributing Institute(s):

1. Selective Vulnerability of Neurodegenerative Diseases (AG Jackson)
2. Genome Biology of Neurodegenerative Diseases (AG Heutink 1)
3. Neurovascular Diseases (AG Petzold)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2022

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