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


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.

Type Journal
ISBN 2589-0042 (Electronic) 2589-0042 (Linking)
Authors Reis, A. L. M.; Hammond, J. M.; Stevanovski, I.; Arnold, J. C.; McGregor, I. S.; Deveson, I. W.; Gururajan, A.
Publisher Name iScience
Published Date 2022-09-16
Published Volume 25
Published Issue 9
Published Pages 104861
Status Published in-print
DOI 10.1016/j.isci.2022.104861
URL link to publisher's version