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Neurogastroenterol Motil. 2015 Dec;27(12):1831-6. doi: 10.1111/nmo.12675. Epub 2015 Sep 25.

Early-life stress-induced visceral hypersensitivity and anxiety behavior is reversed by histone deacetylase inhibition.

Author information

1
Laboratory of Neurogastroenterology, APC Microbiome Institute, University College Cork, Cork, Ireland.
2
Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
3
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

Abstract

Stressful life events, especially in childhood, can have detrimental effects on health and are associated with a host of psychiatric and gastrointestinal disorders including irritable bowel syndrome (IBS). Early-life stress can be recapitulated in animals using the maternal separation (MS) model, exhibiting many key phenotypic outcomes including visceral hypersensitivity and anxiety-like behaviors. The molecular mechanisms of MS are unclear, but recent studies point to a role for epigenetics. Histone acetylation is a key epigenetic mark that is altered in numerous stress-related disease states. Here, we investigated the role of histone acetylation in early-life stress-induced visceral hypersensitivity. Interestingly, increased number of pain behaviors and reduced threshold of visceral sensation were associated with alterations in histone acetylation in the lumbosacral spinal cord, a key region in visceral pain processing. Moreover, we also investigated whether the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA), could reverse early-life stress-induced visceral hypersensitivity and stress-induced fecal pellet output in the MS model. Significantly, SAHA reversed both of these parameters. Taken together, these data describe, for the first time, a key role of histone acetylation in the pathophysiology of early-life stress-induced visceral hypersensitivity in a well-established model of IBS. These findings will inform new research aimed at the development of novel pharmaceutical approaches targeting the epigenetic machinery for novel anti-IBS drugs.

KEYWORDS:

SAHA; epigenetics; histone acetylation; irritable bowel syndrome; stress; visceral pain

PMID:
26403543
DOI:
10.1111/nmo.12675
[Indexed for MEDLINE]

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