Abstract
BackgroundAutism 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.FindingsAfter 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.ConclusionsOur findings of sexual dimorphism in sncRNA levels underscore the importance of considering sex, in addition to age, when interpreting molecular findings on ASD brain.
Highlights
Autism spectrum disorder (ASD) is sexually dimorphic in brain structure, genetics, and behaviors
Our findings of sexual dimorphism in small noncoding RNA (sncRNA) levels underscore the importance of considering sex, in addition to age, when interpreting molecular findings on ASD brain
We focused on two temporal cortical regions: the superior temporal sulcus (STS), a region implicated in social impairments in ASD [19,20,21,22], and the primary auditory cortex (PAC)
Summary
Autism spectrum disorder (ASD) is sexually dimorphic in brain structure, genetics, and behaviors. Autism spectrum disorder (ASD) is one of a number of neurodevelopmental disorders that display sexual dimorphism, occurring more frequently in males, which affect brain structure, gene expression, pathways, function, and behaviors that will require individualized treatments [1,2,3]. Extensive evidence demonstrates sex differences in ASD brain [4,5,6,7]. Females appear to have a higher threshold for being affected by genetic factors than males, requiring a greater genetic burden, and may have greater brain plasticity [8, 9]. Environmental and hormone factors that differ between the sexes, like testosterone, may impact the time course and severity of symptoms [12]
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