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Allele-specific pro...
Allele-specific programming of Npy and epigenetic effects of physical activity in a genetic model of depression
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- Melas, P. A. (author)
- Karolinska Institutet
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- Lennartsson, A. (author)
- Karolinska Institutet
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- Vakifahmetoglu-Norberg, H. (author)
- Karolinska Institutet,Stockholms universitet,Avdelningen för utvecklingsbiologi
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- Wei, Y. (author)
- Karolinska Institutet
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Åberg, E. (author)
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Werme, M. (author)
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Rogdaki, M. (author)
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- Mannervik, Mattias (author)
- Stockholms universitet,Avdelningen för utvecklingsbiologi
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Wegener, G. (author)
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- Brene, S. (author)
- Karolinska Institutet
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- Mathe, A. A. (author)
- Karolinska Institutet
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- Lavebratt, C. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2013-05-07
- 2013
- English.
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In: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 3, s. e255-
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https://doi.org/10.1...
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https://www.nature.c...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Neuropeptide Y (NPY) has been implicated in depression, emotional processing and stress response. Part of this evidence originates from human single-nucleotide polymorphism (SNP) studies. In the present study, we report that a SNP in the rat Npy promoter (C/T; rs105431668) affects in vitro transcription and DNA-protein interactions. Genotyping studies showed that the C-allele of rs105431668 is present in a genetic rat model of depression (Flinders sensitive line; FSL), while the SNP's T-allele is present in its controls (Flinders resistant line; FRL). In vivo experiments revealed binding of a transcription factor (CREB2) and a histone acetyltransferase (Ep300) only at the SNP locus of the FRL. Accordingly, the FRL had increased hippocampal levels of Npy mRNA and H3K18 acetylation; a gene-activating histone modification maintained by Ep300. Next, based on previous studies showing antidepressant-like effects of physical activity in the FSL, we hypothesized that physical activity may affect Npy's epigenetic status. In line with this assumption, physical activity was associated with increased levels of Npy mRNA and H3K18 acetylation. Physical activity was also associated with reduced mRNA levels of a histone deacetylase (Hdac5). Conclusively, the rat rs105431668 appears to be a functional Npy SNP that may underlie depression-like characteristics. In addition, the achieved epigenetic reprogramming of Npy provides molecular support for the putative effectiveness of physical activity as a non-pharmacological antidepressant.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Keyword
- Ep300
- hippocampus
- histone modifications
- mood disorders
- neuropeptide Y
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Melas, P. A.
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Lennartsson, A.
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Vakifahmetoglu-N ...
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Wei, Y.
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Åberg, E.
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Werme, M.
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show more...
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Rogdaki, M.
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Mannervik, Matti ...
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Wegener, G.
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Brene, S.
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Mathe, A. A.
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Lavebratt, C.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
- Articles in the publication
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Translational Ps ...
- By the university
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Stockholm University
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Karolinska Institutet