Analysis of blood transcriptomics of the Djungarian hamster in torpor

Rojas Cuyutupa, Valeria (2025): Analysis of blood transcriptomics of the Djungarian hamster in torpor: a comparative approach with other mammalian species. Dissertation, LMU München: Medizinische Fakultät

Abstract

Torpor is a complex survival strategy where endogenous metabolic rate (MR), respiratory rate and body temperature (Tb) are reversibly reduced to limit energy expenditure during periods of environmental stress. For mammals capable of torpor this process entails vast metabolic changes as they need to maintain their physiological equilibrium for hours, days or even weeks, depending on the type of torpor. During this period the homeostatic machinery is significantly impaired before the euthermic state is regained by spontaneous intrinsic heat production. In this work transcriptional changes related to daily torpor were analysed using the Djungarian hamster (Phodopus sungorus) model. The aim of this work was (i) to evaluate the transcriptional dynamics between the different phases of torpor entry (ZT01), nadir / mid-torpor (ZT04), arousal (ZT07) and post-torpor phase (ZT16), (ii) to identify common transcriptional patterns in the blood of torpid P. sungorus and other torpid / hibernating mammals independent of analysed solid organ, and (iii) to compare blood transcriptome profiles of the different phases of P. sungorus daily torpor with human overwintering crews in Antarctica during different times of the mission to obtain information on possible similarities in regulation of gene expression between torpor and environmental stress related changes in humans. For data analysis the bioinformatic tool Ingenuity Pathway Analysis (IPA) was used to identify the main signalling pathways involved and their respective regulatory pattern. The results showed (i) notable changes between torpor entry (ZT01) and torpor nadir (ZT04), while ZT01 was largely indifferent to control samples. Transcriptional proliferation, translation and protein production machinery were significantly depressed during torpor nadir (ZT04) but were restored and even upregulated during arousal (ZT07), followed by a period of slight depression in the post-torpor phase before full recovery. (ii) Based on IPA key target molecule analysis (TMIPA) most cellular processes are inhibited during torpor nadir (ZT04). By literature comparison of 9 other hibernators and 10 different organs, this inhibition was shown to be independent of torpor type, duration or species. VI Suppression of basic energy-consuming cellular processes, downregulation of proinflammatory immune responses and organ protection predominantly by suspending pro-apoptotic processes and promoting antioxidant production allow entry into torpor / hibernation without signs of tissue damage upon arousal. Furthermore, these data corroborate that the transcriptomic alterations required for torpor / hibernation in general and at the level of specific organs can be detected in and are reflected by blood cells. (iii) Humans overwintering at the Antarctic Concordia station show a similar downregulation pattern of the immune system as observed for ZT04 animals, however most canonical pathways in human samples were more comparable to the arousal phase (ZT07) in animals, mirroring a "continuous arousal" with EIF2, TGF-β signalling, SUMOylation and telomerase signalling as the most upregulated pathways in the overwintering crews. The post phase of human overwintering crews is similar to P. sungorus post phase (ZT16), representing a recovery phase of minor global downregulation striving towards control levels.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: Torpor, Phodopus sungrus, Metabolism, Transcriptom, Torpor phases, Hibernation
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 7. April 2025
• 1. Bericht­erstatter:in: Choukér, Alexander