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Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development.

ABSTRACT: The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon. Restraint stress was applied to pregnant Slc6a4 +/+ and Slc6a4 +/- mice and post-stress embryonic brains were assessed for whole genome level profiling of methylome, transcriptome and miRNA using Next Generation Sequencing. Embryos of stressed Slc6a4 +/+ dams exhibited significantly altered methylation profiles and differential expression of 157 miRNAs and 1009 genes affecting neuron development and cellular adhesion pathways, which may function as a coping mechanism to prenatal stress. In striking contrast, the response of embryos of stressed Slc6a4 +/- dams was found to be attenuated, shown by significantly reduced numbers of differentially expressed genes (458) and miRNA (0) and genome hypermethylation. This attenuated response may pose increased risks on typical brain development resulting in development of ASD-like characteristics in offspring of mothers with deficits in serotonin related pathways during stressful pregnancies.

SUBMITTER: Sjaarda CP

PROVIDER: S-EPMC5562880 | biostudies-other | 2017 Aug

REPOSITORIES: biostudies-other

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Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development.

Sjaarda Calvin P CP Hecht Patrick P McNaughton Amy J M AJM Zhou Audrina A Hudson Melissa L ML Will Matt J MJ Smith Garth G Ayub Muhammad M Liang Ping P Chen Nansheng N Beversdorf David D Liu Xudong X

Scientific reports 20170818 1

The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this mater ...[more]

PMID: 28821725

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Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development.

Publications

Interplay between maternal Slc6a4 mutation and prenatal stress: a possible mechanism for autistic behavior development.

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