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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
Signaling network between the dysregulated expression of microRNAs and mRNAs in propofol-induced developmental
Congshan Jiang1,2, Sarah Logan3,4, Yasheng Yan3
1Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
Abstract:
Mounting evidence has demonstrated that general anesthetics could induce acute neuroapoptosis in developing animals followed by long-term cognitive dysfunction, with the mechanisms remaining largely unknown. The aim of this study was to investigate the effect of the intravenous anesthetic propofol on the profiles of microRNAs (miRNAs) and messenger RNAs (mRNAs), and their interactive signaling networks in the developing mouse hippocampus. Postnatal day 7 (P7) mice were exposed to propofol for 3 hours. Hippocampi were harvested from both P7 (3 hours after exposure) and P60 mice for the analysis of the expression of 726 miRNAs and 24,881 mRNAs, and apoptosis. Long-term memory ability of P60 mice was analyzed using the Morris Water Maze. Propofol induced acute apoptosis in the hippocampus, and impaired memory function of mice. There were 100 altered mRNAs and 18 dysregulated miRNAs in the propofol-treated hippocampi compared with the intralipid-treated control tissues on P7. Bioinformatics analysis of these abnormally expressed genes on P7 indicated that 34 dysregulated miRNA-mRNA target pairs were related to pathological neurological and developmental disorder processes such as cell viability, cell morphology and migration, neural stem cell proliferation and neurogenesis, oligodendrocyte myelination, reactive oxygen species, and calcium signaling. Neonatal propofol exposure also resulted in the abnormal expression of 49 mRNAs and 4 miRNAs in P60 mouse hippocampi. Specifically, bioinformatics analysis indicates that among these dysregulated mRNAs and miRNAs, there were 2 dysregulated miRNA-mRNA targets pairs (Fam46a/miR-363-3p and Rgs3/miR-363-3p) that might be related to the effect of propofol on long-term cognitive function. Collectively, our novel investigation indicates that acute and long-term dysregulated miRNA-mRNA signaling networks potentially participate in propofol-induced developmental neurotoxicity.
Insights
Propofol anesthesia in developing mice causes brain cell death and memory problems. This study reveals altered microRNA (miRNA) and messenger RNA (mRNA) networks, suggesting a mechanism for propofol-induced neurotoxicity.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- General anesthetics can cause neuroapoptosis in developing animals, leading to cognitive deficits.
- The precise mechanisms behind anesthetic-induced neurotoxicity remain largely unknown.
Purpose of the Study:
- To investigate the impact of propofol on microRNA (miRNA) and messenger RNA (mRNA) profiles in the developing mouse hippocampus.
- To identify interactive signaling networks affected by propofol exposure.
Main Methods:
- Postnatal day 7 (P7) mice were exposed to propofol for 3 hours.
- Hippocampal tissues were analyzed for miRNA, mRNA expression, and apoptosis at P7 and P60.
- Cognitive function was assessed using the Morris Water Maze in P60 mice.
Main Results:
- Propofol induced acute apoptosis and impaired memory in mice.
- Significant alterations in miRNA and mRNA expression were observed in the hippocampus post-propofol exposure.
- Bioinformatics analysis identified dysregulated miRNA-mRNA target pairs linked to neurological and developmental processes.
Conclusions:
- Acute propofol exposure alters miRNA-mRNA signaling networks in the developing mouse hippocampus.
- These molecular changes are associated with neuroapoptosis and long-term cognitive dysfunction.
- Dysregulated miRNA-mRNA networks may underlie propofol-induced developmental neurotoxicity.
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