当前位置： SCI文献检索 > MOLECULAR PSYCHIATRY期刊下所有文献 > Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.

Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.

Abstract：

:Genetic factors do not fully account for the relatively high heritability of neurodevelopmental conditions, suggesting that non-genetic heritable factors contribute to their etiology. To evaluate the potential contribution of aberrant thyroid hormone status to the epigenetic inheritance of neurological phenotypes, we examined genetically normal F2 generation descendants of mice that were developmentally overexposed to thyroid hormone due to a Dio3 mutation. Hypothalamic gene expression profiling in postnatal day 15 F2 descendants on the paternal lineage of ancestral male and female T3-overexposed mice revealed, respectively, 1089 and 1549 differentially expressed genes. A large number of them, 675 genes, were common to both sets, suggesting comparable epigenetic effects of thyroid hormone on both the male and female ancestral germ lines. Oligodendrocyte- and neuron-specific genes were strongly overrepresented among genes showing, respectively, increased and decreased expression. Altered gene expression extended to other brain regions and was associated in adulthood with decreased anxiety-like behavior, increased marble burying and reduced physical activity. The sperm of T3-overexposed male ancestors revealed significant hypomethylation of CpG islands associated with the promoters of genes involved in the early development of the central nervous system. Some of them were candidates for neurodevelopmental disorders in humans including Nrg3, Nrxn1, Gabrb3, Gabra5, Apba2, Grik3, Reln, Nsd1, Pcdh8, En1, and Elavl2. Thus, developmental levels of thyroid hormone influence the epigenetic information of the germ line, disproportionately affecting genes with critical roles in early brain development, and leading in future generations to disease-relevant alterations in postnatal brain gene expression and adult behavior.

journal_name

Mol Psychiatry

journal_title

Molecular psychiatry

authors

Martinez ME,Duarte CW,Stohn JP,Karaczyn A,Wu Z,DeMambro VE,Hernandez A

doi

10.1038/s41380-018-0281-4

subject

Has Abstract

pub_date

2020-05-01 00:00:00

pages

939-950

issue

eissn

1359-4184

issn

1476-5578

pii

10.1038/s41380-018-0281-4

journal_volume

pub_type

杂志文章

在线工具

Thyroid hormone influences brain gene expression programs and behaviors in later generations by altering germ line epigenetic information.