Unknown

Dataset Information

0

Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain.


ABSTRACT: Childhood malnutrition is a risk factor for mental disorders, such as major depression and anxiety. Evidence shows that similar early life adversities induce sex-dependent epigenetic reprogramming. However, little is known about how genes are specifically affected by early malnutrition and the implications for males and females respectively. One relevant target is neuropeptide Y (NPY), which regulates both stress and food-intake. We studied maternal low protein diet (LPD) during pregnancy/lactation in mice. Male, but not female, offspring of LPD mothers consistently displayed anxiety- and depression-like behaviors under acute stress. Transcriptome-wide analysis of the effects of acute stress in the amygdala, revealed a list of transcription factors affected by either sex or perinatal LPD. Among these immediate early genes (IEG), members of the Early growth response family (Egr1/2/4) were consistently upregulated by perinatal LPD in both sexes. EGR1 also bound the NPY receptor Y1 gene (Npy1r), which co-occurred with sex-specific effects of perinatal LPD on both Npy1r DNA-methylation and gene transcription. Our proposed pathway connecting early malnutrition, sex-independent regulatory changes in Egr1, and sex-specific epigenetic reprogramming of its effector gene, Npy1r, represents the first molecular evidence of how early life risk factors may generate sex-specific epigenetic effects relevant for mental disorders.

SUBMITTER: Natt D 

PROVIDER: S-EPMC5593991 | BioStudies | 2017-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3405267 | BioStudies
1000-01-01 | S-EPMC5804527 | BioStudies
2019-01-01 | S-EPMC6461999 | BioStudies
1000-01-01 | S-EPMC3228432 | BioStudies
2014-01-01 | S-EPMC4022724 | BioStudies
2019-01-01 | S-EPMC6602956 | BioStudies
1000-01-01 | S-EPMC5490747 | BioStudies
2020-01-01 | S-EPMC6931124 | BioStudies
2017-08-30 | E-MTAB-5496 | ArrayExpress
2013-01-01 | S-EPMC3590300 | BioStudies