Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus

Progressive dysfunction and loss of neurons ultimately culminates in the symptoms and eventual fatality of prion disease, yet the pathways and mechanisms that lead to neuronal degeneration remain elusive. Here, we used RNAseq to profile transcriptional changes in microdissected CA1 and thalamus brai...

Full description

Bibliographic Details
Main Authors: Jessy A. Slota, Sarah J. Medina, Kathy L. Frost, Stephanie A. Booth
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2022.918811/full
_version_ 1811233982773198848
author Jessy A. Slota
Jessy A. Slota
Sarah J. Medina
Kathy L. Frost
Stephanie A. Booth
Stephanie A. Booth
author_facet Jessy A. Slota
Jessy A. Slota
Sarah J. Medina
Kathy L. Frost
Stephanie A. Booth
Stephanie A. Booth
author_sort Jessy A. Slota
collection DOAJ
description Progressive dysfunction and loss of neurons ultimately culminates in the symptoms and eventual fatality of prion disease, yet the pathways and mechanisms that lead to neuronal degeneration remain elusive. Here, we used RNAseq to profile transcriptional changes in microdissected CA1 and thalamus brain tissues from prion infected mice. Numerous transcripts were altered during clinical disease, whereas very few transcripts were reliably altered at pre-clinical time points. Prion altered transcripts were assigned to broadly defined brain cell types and we noted a strong transcriptional signature that was affiliated with reactive microglia and astrocytes. While very few neuronal transcripts were common between the CA1 and thalamus, we described transcriptional changes in both regions that were related to synaptic dysfunction. Using transcriptional profiling to compare how different neuronal populations respond during prion disease may help decipher mechanisms that lead to neuronal demise and should be investigated with greater detail.
first_indexed 2024-04-12T11:29:07Z
format Article
id doaj.art-b93e609511584e249384707caaf117e3
institution Directory Open Access Journal
issn 1662-453X
language English
last_indexed 2024-04-12T11:29:07Z
publishDate 2022-05-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Neuroscience
spelling doaj.art-b93e609511584e249384707caaf117e32022-12-22T03:35:06ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2022-05-011610.3389/fnins.2022.918811918811Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and ThalamusJessy A. Slota0Jessy A. Slota1Sarah J. Medina2Kathy L. Frost3Stephanie A. Booth4Stephanie A. Booth5One Health Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaOne Health Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, CanadaOne Health Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, CanadaOne Health Division, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, CanadaDepartment of Medical Microbiology and Infectious Diseases, Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, CanadaProgressive dysfunction and loss of neurons ultimately culminates in the symptoms and eventual fatality of prion disease, yet the pathways and mechanisms that lead to neuronal degeneration remain elusive. Here, we used RNAseq to profile transcriptional changes in microdissected CA1 and thalamus brain tissues from prion infected mice. Numerous transcripts were altered during clinical disease, whereas very few transcripts were reliably altered at pre-clinical time points. Prion altered transcripts were assigned to broadly defined brain cell types and we noted a strong transcriptional signature that was affiliated with reactive microglia and astrocytes. While very few neuronal transcripts were common between the CA1 and thalamus, we described transcriptional changes in both regions that were related to synaptic dysfunction. Using transcriptional profiling to compare how different neuronal populations respond during prion disease may help decipher mechanisms that lead to neuronal demise and should be investigated with greater detail.https://www.frontiersin.org/articles/10.3389/fnins.2022.918811/fullprionneurodegenerationpathophysiologysynaptic dysfunctionneuroinflammationreactive gliosis
spellingShingle Jessy A. Slota
Jessy A. Slota
Sarah J. Medina
Kathy L. Frost
Stephanie A. Booth
Stephanie A. Booth
Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus
Frontiers in Neuroscience
prion
neurodegeneration
pathophysiology
synaptic dysfunction
neuroinflammation
reactive gliosis
title Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus
title_full Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus
title_fullStr Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus
title_full_unstemmed Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus
title_short Neurons and Astrocytes Elicit Brain Region Specific Transcriptional Responses to Prion Disease in the Murine CA1 and Thalamus
title_sort neurons and astrocytes elicit brain region specific transcriptional responses to prion disease in the murine ca1 and thalamus
topic prion
neurodegeneration
pathophysiology
synaptic dysfunction
neuroinflammation
reactive gliosis
url https://www.frontiersin.org/articles/10.3389/fnins.2022.918811/full
work_keys_str_mv AT jessyaslota neuronsandastrocyteselicitbrainregionspecifictranscriptionalresponsestopriondiseaseinthemurineca1andthalamus
AT jessyaslota neuronsandastrocyteselicitbrainregionspecifictranscriptionalresponsestopriondiseaseinthemurineca1andthalamus
AT sarahjmedina neuronsandastrocyteselicitbrainregionspecifictranscriptionalresponsestopriondiseaseinthemurineca1andthalamus
AT kathylfrost neuronsandastrocyteselicitbrainregionspecifictranscriptionalresponsestopriondiseaseinthemurineca1andthalamus
AT stephanieabooth neuronsandastrocyteselicitbrainregionspecifictranscriptionalresponsestopriondiseaseinthemurineca1andthalamus
AT stephanieabooth neuronsandastrocyteselicitbrainregionspecifictranscriptionalresponsestopriondiseaseinthemurineca1andthalamus