Sex-Dependent Changes of miRNA Levels in the Hippocampus of Adrenalectomized Rats following Acute Corticosterone Administration

Wladimir A. Corrales, Juan P. Silva, Claudio S. Parra, Felipe A. Olave, Felipe I. Aguayo, Luciano Román-Albasini, Esteban Aliaga, Leslye Venegas-Zamora, Ana M. Avalos, Paulina S. Rojas, Vinicius Maracaja-Coutinho, Robert H. Oakley, John A. Cidlowski, Jenny L. Fiedler

Research output: Contribution to journalArticlepeer-review

Abstract

We explored sex-biased effects of the primary stress glucocorticoid hormone corticosterone on the miRNA expression profile in the rat hippocampus. Adult adrenalectomized (ADX) female and male rats received a single corticosterone (10 mg/kg) or vehicle injection, and after 6 h, hippocampi were collected for miRNA, mRNA, and Western blot analyses. miRNA profiling microarrays showed a basal sex-biased miRNA profile in ADX rat hippocampi. Additionally, acute corticosterone administration triggered a sex-biased differential expression of miRNAs derived from genes located in several chromosomes and clusters on the X and 6 chromosomes. Putative promoter analysis unveiled that most corticosterone-responsive miRNA genes contained motifs for either direct or indirect glucocorticoid actions in both sexes. The evaluation of transcription factors indicated that almost 50% of miRNA genes sensitive to corticosterone in both sexes was under glucocorticoid receptor regulation. Transcription factor-miRNA regulatory network analyses identified several transcription factors that regulate, activate, or repress miRNA expression. Validated target mRNA analysis of corticosterone-responsive miRNAs showed a more complex miRNA-mRNA interaction network in males compared to females. Enrichment analysis revealed that several hippocampal-relevant pathways were affected in both sexes, such as neurogenesis and neurotrophin signaling. The evaluation of selected miRNA targets from these pathways displayed a strong sex difference in the hippocampus of ADX-vehicle rats. Corticosterone treatment did not change the levels of the miRNA targets and their corresponding tested proteins. Our data indicate that corticosterone exerts a sex-biased effect on hippocampal miRNA expression, which may engage in sculpting the basal sex differences observed at higher levels of hippocampal functioning.

Original languageEnglish
Pages (from-to)2981-3001
Number of pages21
JournalACS Chemical Neuroscience
Volume12
Issue number16
DOIs
Publication statusPublished - 18 Aug 2021

Keywords

  • Adrenalectomy
  • corticosterone
  • glucocorticoid receptors
  • hippocampus
  • miRNAs
  • sex bias

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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