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Perinatal Malnutrit...
Perinatal Malnutrition Leads to Sexually Dimorphic Behavioral Responses with Associated Epigenetic Changes in the Mouse Brain
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- Nätt, Daniel (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Columbia University, NY 10027 USA
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- Barchiesi, Riccardo (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Murad, Josef (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Feng, Jian (author)
- Florida State University, FL 32306 USA; Icahn School Medical Mt Sinai, NY 10029 USA
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- Nestler, Eric J. (author)
- Icahn School Medical Mt Sinai, USA
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- Champagne, Frances A. (author)
- Columbia University, USA
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- Thorsell, Annika (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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(creator_code:org_t)
- 2017-09-11
- 2017
- English.
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
- Related links:
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https://liu.diva-por... (primary) (Raw object)
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https://www.nature.c...
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https://doi.org/10.1...
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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