Allele-specific programming of Npy and epigenetic effects of physical activity in a genetic model of depression

作者：Melas P A^*; Lennartsson A; Vakifahmetoglu Norberg H; Wei Y; Aberg E; Werme M; Rogdaki M; Mannervik M; Wegener G; Brene S; Mathe A A; Lavebratt C

来源：Translational Psychiatry, 2013, 3(5): e255.

DOI：10.1038/tp.2013.31

• Ep300
• hippocampus
• histone modifications
• mood disorders
• neuropeptide Y

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%26apos;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%26apos;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.

• 出版日期2013-5
• 单位西北大学