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Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study

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Abstract

Purpose

To evaluate the effects of sex on miRNA expression in the hippocampus after isoflurane anesthesia in a neonatal piglet model.

Methods

Six male and 6 female piglets, aged 3–5 days, were anesthetized with 2% isoflurane in room air for 3 h. Full physiologic monitoring was observed. Untreated animals (6 male, 6 female) served as controls. Expression of miRNAs in hippocampus was assessed.

Results

In controls, miRNA expression in the hippocampus was highly conserved between males and females. However, 17/326 displayed sex-dependent differences: 10 miRNAs were more highly expressed in males; 7 showed lower expression in males than females. Isoflurane was associated with changes in the expression of distinct subsets of miRNAs in both males and females. In females, 14/326 miRNAs were significantly changed (3 downregulated; 11 upregulated); in males, 17/326 miRNAs were changed (7 downregulated; 10 upregulated). There was no overlap in significantly changed miRNAs between isoflurane-exposed males and females.

Conclusions

In the neonatal piglet hippocampus, miRNA expression was highly conserved. There was no overlap in miRNA expression between isoflurane-exposed males and females, suggesting sex differences in isoflurane-induced miRNA expression. These results support the hypothesis that a clinically relevant exposure to isoflurane induces distinct miRNA signatures in the hippocampus of neonatal male and female piglets. Their functional relevance in anesthesia-induced neurotoxicity remains unknown, although changes in specific miRNAs may either contribute to or protect against anesthesia-induced neurotoxicity.

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Acknowledgements

We thank the Genomics Shared Resource at The Ohio State University Comprehensive Cancer Center (OSU CCC), Columbus, OH for conducting the Affymetrix GeneChip® miRNA 4.0 Array analyses. This work was supported in part by the OSU CCC and the National Institutes of Health Grant P30 CA16058.

Funding

This study was generously supported by departmental start-up funds [EW], a Nationwide Children’s Hospital, Internal Funds, Intramural Grant [EW], and the Ohio State University Center for Clinical and Translational Science Davis-Bremer Pre-K Award [EW]. This work was also supported in part by the OSU College of Medicine Roessler research scholarship [BW, JX]. EW is also supported by an NIH Institute for Child Health and Development, Loan Repayment Award, NIH LRP grant, funded by the NIH NICHD to investigate potential neurotoxicity mechanisms of anesthetics in a neonatal piglet model. FLC has received support from NIH R01 NIDDK Grants DK093499 and DK133943, as well as a Dean’s Bridge Grant from the OSU Office of Research. miRNA analysis was supported in part by NCI P30CA016058 Shared Resource Funds.

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Authors and Affiliations

  1. Department of Anesthesiology, University of Vermont Larner College of Medicine, 111 Colchester Avenue, Burlington, VT, 05401, USA

    Emmett E. Whitaker

  2. Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, USA

    Emmett E. Whitaker

  3. Medical Student Research Program, Ohio State University College of Medicine, Columbus, USA

    Brianne Z. Wiemann & Jason C. Xia

  4. Department of Anaesthesia and Critical Care Medicine, University of Toronto, Toronto, Canada

    Bruno Bissonnette

  5. Comprehensive Cancer Center, Ohio State University, Columbus, USA

    Paolo Fadda

  6. Department of Anesthesiology, Nationwide Children’s Hospital, Columbus, USA

    Joseph Liu & Joseph D. Tobias

  7. Department of Anesthesiology, Ohio State University, Columbus, USA

    Joseph D. Tobias & Fievos L. Christofi

Authors
  1. Emmett E. Whitaker
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  2. Brianne Z. Wiemann
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  3. Jason C. Xia
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  4. Bruno Bissonnette
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  5. Joseph Liu
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  7. Joseph D. Tobias
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  8. Fievos L. Christofi
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Corresponding author

Correspondence to Emmett E. Whitaker.

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No conflicts of interest declared.

Ethical approval

This study was approved by The Ohio State University Institutional Animal Care and Use Committee (IACUC), protocol # 2014A00000018.

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Whitaker, E.E., Wiemann, B.Z., Xia, J.C. et al. Distinct, sex-dependent miRNA signatures in piglet hippocampus induced by a clinically relevant isoflurane exposure: a pilot study. J Anesth 33, 670–679 (2019). https://doi.org/10.1007/s00540-019-02695-5

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  • DOI: https://doi.org/10.1007/s00540-019-02695-5

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