Sex-specific transcriptomic and epitranscriptomic signatures of PTSD-like fear acquisition.

Behavioral neuroscience Molecular biology Molecular mechanism of behavior Omics Transcriptomics

Journal

iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038

Informations de publication

Date de publication:
16 Sep 2022
Historique:
received: 25 04 2022
revised: 03 07 2022
accepted: 26 07 2022
entrez: 30 8 2022
pubmed: 31 8 2022
medline: 31 8 2022
Statut: epublish

Résumé

Our understanding of the molecular pathology of posttraumatic stress disorder (PTSD) is evolving due to advances in sequencing technologies. With the recent emergence of Oxford Nanopore direct RNA-seq (dRNA-seq), it is now also possible to interrogate diverse RNA modifications, collectively known as the "epitranscriptome.". Here, we present our analyses of the male and female mouse amygdala transcriptome and epitranscriptome, obtained using parallel Illumina RNA-seq and Oxford Nanopore dRNA-seq, associated with the acquisition of PTSD-like fear induced by Pavlovian cued-fear conditioning. We report significant sex-specific differences in the amygdala transcriptional response during fear acquisition and a range of shared and dimorphic epitranscriptomic signatures. Differential RNA modifications are enriched among mRNA transcripts associated with neurotransmitter regulation and mitochondrial function, many of which have been previously implicated in PTSD. Very few differentially modified transcripts are also differentially expressed, suggesting an influential, expression-independent role for epitranscriptional regulation in PTSD-like fear acquisition.

Identifiants

pubmed: 36039298
doi: 10.1016/j.isci.2022.104861
pii: S2589-0042(22)01133-6
pmc: PMC9418440
doi:

Types de publication

Journal Article

Langues

eng

Pagination

104861

Informations de copyright

© 2022 The Author(s).

Déclaration de conflit d'intérêts

IWD manages a fee-for-service nanopore sequencing facility at the Garvan Institute of Medical Research that is a customer of Oxford Nanopore Technologies but has no further financial relationship. The authors declare no other competing financial or nonfinancial interests.

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Auteurs

Andre L M Reis (ALM)

Genomics Pillar, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, Australia.

Jillian M Hammond (JM)

Genomics Pillar, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, Australia.

Igor Stevanovski (I)

Genomics Pillar, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, Australia.

Jonathon C Arnold (JC)

Faculty of Medicine and Health, Sydney Pharmacy School, Discipline of Pharmacology, The University of Sydney, Sydney, NSW 2050, Australia.
Brain & Mind Centre, The University of Sydney, Sydney, NSW 2050, Australia.
The Lambert Initiative for Cannabinoid Therapeutics, Australia.

Iain S McGregor (IS)

Brain & Mind Centre, The University of Sydney, Sydney, NSW 2050, Australia.
The Lambert Initiative for Cannabinoid Therapeutics, Australia.
School of Psychology, Faculty of Science, The University of Sydney, Sydney, NSW 2050, Australia.

Ira W Deveson (IW)

Genomics Pillar, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia.
Centre for Population Genomics, Garvan Institute of Medical Research and Murdoch Children's Research Institute, Sydney, Australia.
School of Clinical Medicine, Faculty of Medicine and Health, UNSW Sydney, Sydney, NSW 2010, Australia.

Anand Gururajan (A)

Brain & Mind Centre, The University of Sydney, Sydney, NSW 2050, Australia.

Classifications MeSH