Sex differences in microRNA expression during developmentin rat cortex

Stephanie J. Murphy, Theresa A. Lusardi, Jay I. Phillips, Julie Saugstad

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

There are important sex differences in the risk and outcome of conditions and diseases between males and females. For example, stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage following an ischemic event compared to females. Studies suggest that the difference in male and female susceptibility to ischemia may be triggered by innate variations in gene regulation and protein expression between the sexes that are independent of post-natal exposure to sex hormones. We have shown that there are differences in microRNA (miRNA) expression in adult male and female brain following focal cerebral ischemia in mouse cortex. Herein we examine a role for differential expression of miRNAs during development in male and female rat cortex as potential effectors of the phenotype that leads to sex differences to ischemia. Expression studies in male and female cortices isolated from postnatal day 0 (P0), postnatal day 7 (P7), and adult rats using TaqMan Low Density miRNA arrays and NanoString nCounter analysis revealed differential miRNA levels between males and females at each developmental stage. We focused on the miR-200 family of miRNAs that showed higher levels in females at P0, but higher levels in males at P7 that persisted into adulthood, and validated the expression of miR-200a, miR-200b, and miR-429 by individual qRT-PCR as these are clustered on chromosome 5 and may be transcriptionally co-regulated. Prediction analysis of the miR-200 miRNAs revealed that genes within the Gonadotropin releasing hormone receptor pathway are the most heavily targeted. These studies support that developmental changes in miRNA expression may influence phenotypes in adult brain that underlie sexually dimorphic responses to disease, including ischemia.

Original languageEnglish (US)
Pages (from-to)24-32
Number of pages9
JournalNeurochemistry International
Volume77
DOIs
StatePublished - 2014

Fingerprint

MicroRNAs
Sex Characteristics
Ischemia
Brain Ischemia
Brain
LHRH Receptors
Phenotype
Chromosomes, Human, Pair 5
Gonadal Steroid Hormones
Ethnic Groups
Stroke
Polymerase Chain Reaction
Genes
Proteins

Keywords

  • Cortex
  • Development
  • Disease outcome
  • MicroRNA
  • Rat
  • Sex

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Sex differences in microRNA expression during developmentin rat cortex. / Murphy, Stephanie J.; Lusardi, Theresa A.; Phillips, Jay I.; Saugstad, Julie.

In: Neurochemistry International, Vol. 77, 2014, p. 24-32.

Research output: Contribution to journalArticle

Murphy, Stephanie J. ; Lusardi, Theresa A. ; Phillips, Jay I. ; Saugstad, Julie. / Sex differences in microRNA expression during developmentin rat cortex. In: Neurochemistry International. 2014 ; Vol. 77. pp. 24-32.
@article{ceda65c12dde4a329f7fa4a3855735f0,
title = "Sex differences in microRNA expression during developmentin rat cortex",
abstract = "There are important sex differences in the risk and outcome of conditions and diseases between males and females. For example, stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage following an ischemic event compared to females. Studies suggest that the difference in male and female susceptibility to ischemia may be triggered by innate variations in gene regulation and protein expression between the sexes that are independent of post-natal exposure to sex hormones. We have shown that there are differences in microRNA (miRNA) expression in adult male and female brain following focal cerebral ischemia in mouse cortex. Herein we examine a role for differential expression of miRNAs during development in male and female rat cortex as potential effectors of the phenotype that leads to sex differences to ischemia. Expression studies in male and female cortices isolated from postnatal day 0 (P0), postnatal day 7 (P7), and adult rats using TaqMan Low Density miRNA arrays and NanoString nCounter analysis revealed differential miRNA levels between males and females at each developmental stage. We focused on the miR-200 family of miRNAs that showed higher levels in females at P0, but higher levels in males at P7 that persisted into adulthood, and validated the expression of miR-200a, miR-200b, and miR-429 by individual qRT-PCR as these are clustered on chromosome 5 and may be transcriptionally co-regulated. Prediction analysis of the miR-200 miRNAs revealed that genes within the Gonadotropin releasing hormone receptor pathway are the most heavily targeted. These studies support that developmental changes in miRNA expression may influence phenotypes in adult brain that underlie sexually dimorphic responses to disease, including ischemia.",
keywords = "Cortex, Development, Disease outcome, MicroRNA, Rat, Sex",
author = "Murphy, {Stephanie J.} and Lusardi, {Theresa A.} and Phillips, {Jay I.} and Julie Saugstad",
year = "2014",
doi = "10.1016/j.neuint.2014.06.007",
language = "English (US)",
volume = "77",
pages = "24--32",
journal = "Neurochemistry International",
issn = "0197-0186",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Sex differences in microRNA expression during developmentin rat cortex

AU - Murphy, Stephanie J.

AU - Lusardi, Theresa A.

AU - Phillips, Jay I.

AU - Saugstad, Julie

PY - 2014

Y1 - 2014

N2 - There are important sex differences in the risk and outcome of conditions and diseases between males and females. For example, stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage following an ischemic event compared to females. Studies suggest that the difference in male and female susceptibility to ischemia may be triggered by innate variations in gene regulation and protein expression between the sexes that are independent of post-natal exposure to sex hormones. We have shown that there are differences in microRNA (miRNA) expression in adult male and female brain following focal cerebral ischemia in mouse cortex. Herein we examine a role for differential expression of miRNAs during development in male and female rat cortex as potential effectors of the phenotype that leads to sex differences to ischemia. Expression studies in male and female cortices isolated from postnatal day 0 (P0), postnatal day 7 (P7), and adult rats using TaqMan Low Density miRNA arrays and NanoString nCounter analysis revealed differential miRNA levels between males and females at each developmental stage. We focused on the miR-200 family of miRNAs that showed higher levels in females at P0, but higher levels in males at P7 that persisted into adulthood, and validated the expression of miR-200a, miR-200b, and miR-429 by individual qRT-PCR as these are clustered on chromosome 5 and may be transcriptionally co-regulated. Prediction analysis of the miR-200 miRNAs revealed that genes within the Gonadotropin releasing hormone receptor pathway are the most heavily targeted. These studies support that developmental changes in miRNA expression may influence phenotypes in adult brain that underlie sexually dimorphic responses to disease, including ischemia.

AB - There are important sex differences in the risk and outcome of conditions and diseases between males and females. For example, stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage following an ischemic event compared to females. Studies suggest that the difference in male and female susceptibility to ischemia may be triggered by innate variations in gene regulation and protein expression between the sexes that are independent of post-natal exposure to sex hormones. We have shown that there are differences in microRNA (miRNA) expression in adult male and female brain following focal cerebral ischemia in mouse cortex. Herein we examine a role for differential expression of miRNAs during development in male and female rat cortex as potential effectors of the phenotype that leads to sex differences to ischemia. Expression studies in male and female cortices isolated from postnatal day 0 (P0), postnatal day 7 (P7), and adult rats using TaqMan Low Density miRNA arrays and NanoString nCounter analysis revealed differential miRNA levels between males and females at each developmental stage. We focused on the miR-200 family of miRNAs that showed higher levels in females at P0, but higher levels in males at P7 that persisted into adulthood, and validated the expression of miR-200a, miR-200b, and miR-429 by individual qRT-PCR as these are clustered on chromosome 5 and may be transcriptionally co-regulated. Prediction analysis of the miR-200 miRNAs revealed that genes within the Gonadotropin releasing hormone receptor pathway are the most heavily targeted. These studies support that developmental changes in miRNA expression may influence phenotypes in adult brain that underlie sexually dimorphic responses to disease, including ischemia.

KW - Cortex

KW - Development

KW - Disease outcome

KW - MicroRNA

KW - Rat

KW - Sex

UR - http://www.scopus.com/inward/record.url?scp=84907585564&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907585564&partnerID=8YFLogxK

U2 - 10.1016/j.neuint.2014.06.007

DO - 10.1016/j.neuint.2014.06.007

M3 - Article

VL - 77

SP - 24

EP - 32

JO - Neurochemistry International

JF - Neurochemistry International

SN - 0197-0186

ER -