Possible Sexually Dimorphic Role of MiRNA and Other SncRNA in ASD Brain

Overview

Journal Mol Autism

Publisher Biomed Central

Date 2017 Feb 11

PMID 28184278

Citations 16

Authors

Cynthia M Schumann

Frank R Sharp

Bradley P Ander

Boryana Stamova

Affiliations

Soon will be listed here.

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.

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References

Hutchison E, Kawamoto E, Taub D, Lal A, Abdelmohsen K, Zhang Y . Evidence for miR-181 involvement in neuroinflammatory responses of astrocytes. Glia. 2013; 61(7):1018-28. PMC: 4624280. DOI: 10.1002/glia.22483. View

Dai R, McReynolds S, LeRoith T, Heid B, Liang Z, Ahmed S . Sex differences in the expression of lupus-associated miRNAs in splenocytes from lupus-prone NZB/WF1 mice. Biol Sex Differ. 2013; 4(1):19. PMC: 3843556. DOI: 10.1186/2042-6410-4-19. View

Rynkiewicz A, Lucka I, Grabowski K . Letter to Editor. Report "An investigation of the 'female camouflage effect' in autism using a new computerized test showing sex/gender differences during ADOS-2". IMFAR 2016, Baltimore, USA. Psychiatr Pol. 2016; 50(3):663-6. DOI: 10.12740/PP/63178. View

Werling D, Geschwind D . Sex differences in autism spectrum disorders. Curr Opin Neurol. 2013; 26(2):146-53. PMC: 4164392. DOI: 10.1097/WCO.0b013e32835ee548. View

Chow M, Pramparo T, Winn M, Barnes C, Li H, Weiss L . Age-dependent brain gene expression and copy number anomalies in autism suggest distinct pathological processes at young versus mature ages. PLoS Genet. 2012; 8(3):e1002592. PMC: 3310790. DOI: 10.1371/journal.pgen.1002592. View

Nordahl C, Iosif A, Young G, Perry L, Dougherty R, Lee A . Sex differences in the corpus callosum in preschool-aged children with autism spectrum disorder. Mol Autism. 2015; 6:26. PMC: 4429319. DOI: 10.1186/s13229-015-0005-4. View

Lai M, Baron-Cohen S, Buxbaum J . Understanding autism in the light of sex/gender. Mol Autism. 2015; 6:24. PMC: 4429357. DOI: 10.1186/s13229-015-0021-4. View

Gockley J, Willsey A, Dong S, Dougherty J, Constantino J, Sanders S . The female protective effect in autism spectrum disorder is not mediated by a single genetic locus. Mol Autism. 2015; 6:25. PMC: 4429476. DOI: 10.1186/s13229-015-0014-3. View

Alaerts K, Nayar K, Kelly C, Raithel J, Milham M, Di Martino A . Age-related changes in intrinsic function of the superior temporal sulcus in autism spectrum disorders. Soc Cogn Affect Neurosci. 2015; 10(10):1413-23. PMC: 4590540. DOI: 10.1093/scan/nsv029. View

10.

Pantelis P, Byrge L, Michael Tyszka J, Adolphs R, Kennedy D . A specific hypoactivation of right temporo-parietal junction/posterior superior temporal sulcus in response to socially awkward situations in autism. Soc Cogn Affect Neurosci. 2015; 10(10):1348-56. PMC: 4590532. DOI: 10.1093/scan/nsv021. View

11.

Kos A, Klein-Gunnewiek T, Meinhardt J, Olde Loohuis N, van Bokhoven H, Kaplan B . MicroRNA-338 Attenuates Cortical Neuronal Outgrowth by Modulating the Expression of Axon Guidance Genes. Mol Neurobiol. 2016; 54(5):3439-3452. PMC: 5658782. DOI: 10.1007/s12035-016-9925-z. View

12.

Werling D, Parikshak N, Geschwind D . Gene expression in human brain implicates sexually dimorphic pathways in autism spectrum disorders. Nat Commun. 2016; 7:10717. PMC: 4762891. DOI: 10.1038/ncomms10717. View

13.

Saitovitch A, Bargiacchi A, Chabane N, Brunelle F, Samson Y, Boddaert N . Social cognition and the superior temporal sulcus: implications in autism. Rev Neurol (Paris). 2012; 168(10):762-70. DOI: 10.1016/j.neurol.2012.07.017. View

14.

Ander B, Barger N, Stamova B, Sharp F, Schumann C . Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders. Mol Autism. 2015; 6:37. PMC: 4491207. DOI: 10.1186/s13229-015-0029-9. View

15.

Vargas J, Kar A, Kowalak J, Gale J, Aschrafi A, Chen C . Axonal localization and mitochondrial association of precursor microRNA 338. Cell Mol Life Sci. 2016; 73(22):4327-4340. PMC: 5056120. DOI: 10.1007/s00018-016-2270-6. View

16.

Mottron L, Duret P, Mueller S, Moore R, Forgeot dArc B, Jacquemont S . Sex differences in brain plasticity: a new hypothesis for sex ratio bias in autism. Mol Autism. 2015; 6:33. PMC: 4456778. DOI: 10.1186/s13229-015-0024-1. View

17.

Constantino J . Data from the Baby Siblings Research Consortium confirm and specify the nature of the female protective effect in autism: A commentary on Messinger et al. Mol Autism. 2016; 7:32. PMC: 4926292. DOI: 10.1186/s13229-016-0092-x. View

18.

Ziats M, Rennert O . Sex-biased gene expression in the developing brain: implications for autism spectrum disorders. Mol Autism. 2013; 4(1):10. PMC: 3653724. DOI: 10.1186/2040-2392-4-10. View

19.

Campbell D, Chang J, Chawarska K . Early generalized overgrowth in autism spectrum disorder: prevalence rates, gender effects, and clinical outcomes. J Am Acad Child Adolesc Psychiatry. 2014; 53(10):1063-73.e5. PMC: 4173120. DOI: 10.1016/j.jaac.2014.07.008. View

20.

Glazov E, McWilliam S, Barris W, Dalrymple B . Origin, evolution, and biological role of miRNA cluster in DLK-DIO3 genomic region in placental mammals. Mol Biol Evol. 2008; 25(5):939-48. DOI: 10.1093/molbev/msn045. View