McKibben, Lauren A;
Iyer, Meghna;
Zhao, Ying;
Florea, Roxana;
Kuhl-Chimera, Sophia;
Deliwala, Ishani;
Pan, Yue;
... Linnstaedt, Sarah D; + view all
(2025)
Transcriptional changes across tissue and time provide molecular insights into a therapeutic window of opportunity following traumatic stress exposure.
Translational Psychiatry
, 15
(1)
, Article 244. 10.1038/s41398-025-03451-y.
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Abstract
Unfortunately, survivors of traumatic stress exposure (TSE) frequently develop adverse posttraumatic neuropsychiatric sequelae (APNS) such as chronic pain and stress/depressive symptoms. Increasing evidence indicates that there is a ‘window of opportunity’ following TSE in which therapeutic interventions are most effective against APNS, yet mechanisms accounting for this observation are poorly understood. Here, we aimed to better understand such mechanisms by generating snapshots of the transcriptional landscape in the early aftermath of TSE across tissues and time. Adult rats were exposed to a TSE model, single prolonged stress (SPS). Then, eight tissues (hypothalamus, left and right hippocampus, amygdala, dorsal root ganglia, spinal cord, heart, and muscle) were isolated from these animals at 2, 24, and 72 h after SPS and in unexposed controls (n = 6 per group). mRNA expression from deep sequencing was used to identify differentially expressed genes (DEGs), biological pathways enriched over time, and predicted upstream regulators. In all tissues except the amygdala, the highest number of DEGs was observed 2-h post-SPS, but DEGs were detected at all timepoints and in all tissues. Some transcripts were differentially expressed in a consistent manner across multiple tissues at a time point (e.g. Fkbp5, 2 h post-SPS), while others had tissue- or region-specific expression patterns. Stress system pathways were most represented at 2 h post-SPS, then stress/circadian/inflammatory pathways at 24 h, and inflammatory pathways at 72 h. Together these findings provide insights into post-TSE transcriptional landscape dynamics and suggest specific intervention windows of opportunity. Future validation is needed across sex, age, stressor, and cell type.
| Type: | Article |
|---|---|
| Title: | Transcriptional changes across tissue and time provide molecular insights into a therapeutic window of opportunity following traumatic stress exposure |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41398-025-03451-y |
| Publisher version: | https://doi.org/10.1038/s41398-025-03451-y |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Psychiatry, SINGLE-PROLONGED STRESS, MENTAL-HEALTH, ANIMAL-MODEL, CHRONIC PAIN, MESSENGER-RNA, PTSD SYMPTOMS, DISORDER, EXPRESSION, RECEPTOR, ALCOHOL |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212231 |
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