Early Brain microRNA/mRNA Expression is Region-Specific After Neonatal Hypoxic-Ischemic Injury in a Mouse Model

Eric S Peeples; Namood-E Sahar; William Snyder; Karoly Mirnics

doi:10.3389/fgene.2022.841043

Early Brain microRNA/mRNA Expression is Region-Specific After Neonatal Hypoxic-Ischemic Injury in a Mouse Model

Front Genet. 2022 Feb 16:13:841043. doi: 10.3389/fgene.2022.841043. eCollection 2022.

Authors

Eric S Peeples^{1

2

3}, Namood-E Sahar^{1

3}, William Snyder^{1

3}, Karoly Mirnics^{3

4

5

6}

Affiliations

¹ Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, United States.
² Department of Pediatrics, Children's Hospital & Medical Center, Omaha, NE, United States.
³ Child Health Research Institute, Omaha, NE, United States.
⁴ Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, United States.
⁵ Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, United States.
⁶ Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, United States.

Abstract

Background: MicroRNAs (miRNAs) may be promising therapeutic targets for neonatal hypoxic-ischemic brain injury (HIBI) but targeting miRNA-based therapy will require more precise understanding of endogenous brain miRNA expression. Methods: Postnatal day 9 mouse pups underwent HIBI by unilateral carotid ligation + hypoxia or sham surgery. Next-generation miRNA sequencing and mRNA Neuroinflammation panels were performed on ipsilateral cortex, striatum/thalamus, and cerebellum of each group at 30 min after injury. Targeted canonical pathways were predicted by KEGG analysis. Results: Sixty-one unique miRNAs showed differential expression (DE) in at least one region; nine in more than one region, including miR-410-5p, -1264-3p, 1298-5p, -5,126, and -34b-3p. Forty-four mRNAs showed DE in at least one region; 16 in more than one region. MiRNAs showing DE primarily targeted metabolic pathways, while mRNAs targeted inflammatory and cell death pathways. Minimal miRNA-mRNA interactions were seen at 30 min after HIBI. Conclusion: This study identified miRNAs that deserve future study to assess their potential as therapeutic targets in neonatal HIBI. Additionally, the differences in miRNA expression between regions suggest that future studies assessing brain miRNA expression to guide therapy development should consider evaluating individual brain regions rather than whole brain to ensure the sensitivity needed for the development of targeted therapies.

Keywords: cerebellum; cortex; encephalopathy; next-generation sequencing; striatum.