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Mol Autism. 2017 Feb 7;8:4. doi: 10.1186/s13229-017-0117-0. eCollection 2017.

Possible sexually dimorphic role of miRNA and other sncRNA in ASD brain.

Author information

1
Department of Psychiatry and Behavioral Sciences, University of California at Davis, School of Medicine, 2805 50th Street, Sacramento, CA 95817 USA.
2
MIND Institute, University of California, 2805 50th Street, Sacramento, CA 95817 USA.
3
Department of Neurology, University of California at Davis, School of Medicine, 2805 50th Street, Sacramento, CA 95817 USA.

Abstract

BACKGROUND:

Autism spectrum disorder (ASD) is sexually dimorphic in brain structure, genetics, and behaviors. In studies of brain tissue, the age of the population is clearly a factor in interpreting study outcome, yet sex is rarely considered. To begin to address this issue, we extend our previously published microarray analyses to examine expression of small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), in ASD and in the control temporal cortex in males and females. Predicted miRNA targets were identified as well as the pathways they overpopulate.

FINDINGS:

After considering age, sexual dimorphism in ASD sncRNA expression persists in the temporal cortex and in the patterning that distinguishes regions. Among the sexually dimorphic miRNAs are miR-219 and miR-338, which promote oligodendrocyte differentiation, miR-125, implicated in neuronal differentiation, and miR-488, implicated in anxiety. Putative miRNA targets are significantly over-represented in immune and nervous system pathways in both sexes, consistent with previous mRNA studies. Even for common pathways, the specific target mRNAs are often sexually dimorphic. For example, both male and female target genes significantly populate the Axonal Guidance Signaling pathway, yet less than a third of the targets are common to both sexes.

CONCLUSIONS:

Our findings of sexual dimorphism in sncRNA levels underscore the importance of considering sex, in addition to age, when interpreting molecular findings on ASD brain.

KEYWORDS:

Auditory cortex; Autism; Myelin; Oligodendrocytes; Postmortem human brain; Sex; Sexual dimorphism; Superior Temporal Sulcus; miR-125; miR-181; miR-219; miR-338; miR-448; microRNA; small noncoding RNA

PMID:
28184278
PMCID:
PMC5294827
DOI:
10.1186/s13229-017-0117-0
[Indexed for MEDLINE]
Free PMC Article

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