Emmett E Whitaker1,2, Brianne Z Wiemann3, Jason C Xia3, Bruno Bissonnette4, Joseph Liu5, Paolo Fadda6, Joseph D Tobias5,7, Fievos L Christofi7. 1. Department of Anesthesiology, University of Vermont Larner College of Medicine, 111 Colchester Avenue, Burlington, VT, 05401, USA. Emmett.Whitaker@UVMHealth.org. 2. Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, USA. Emmett.Whitaker@UVMHealth.org. 3. Medical Student Research Program, Ohio State University College of Medicine, Columbus, USA. 4. Department of Anaesthesia and Critical Care Medicine, University of Toronto, Toronto, Canada. 5. Department of Anesthesiology, Nationwide Children's Hospital, Columbus, USA. 6. Comprehensive Cancer Center, Ohio State University, Columbus, USA. 7. Department of Anesthesiology, Ohio State University, Columbus, USA.
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.
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.
Entities:
Keywords:
Isoflurane; Pediatric anesthesia; Piglet; Sex differences; miRNAs
Authors: Mary M Niblock; Catherine J Luce; Richard A Belliveau; David S Paterson; Michelle L Kelly; Lynn A Sleeper; James J Filiano; Hannah C Kinney Journal: Brain Res Brain Res Rev Date: 2005-07-25
Authors: Emmett E Whitaker; Bruno Bissonnette; Andrew D Miller; Tanner L Koppert; Joseph D Tobias; Christopher R Pierson; Fievos L Christofi Journal: Clin Transl Med Date: 2016-01-12