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Complex regulation of the regulator of synaptic plasticity histone deacetylase 2 in the rodent dorsal horn after peripheral injury

Maiarù, M; Morgan, OB; Tochiki, KK; Hobbiger, EJ; Rajani, K; Overington, DW; Géranton, SM; (2016) Complex regulation of the regulator of synaptic plasticity histone deacetylase 2 in the rodent dorsal horn after peripheral injury. Journal of Neurochemistry , 138 (2) pp. 222-232. 10.1111/jnc.13621. Green open access

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Abstract

Histone deacetylases (HDACs), HDAC2 in particular, have been shown to regulate various forms of learning and memory. Since cognitive processes share mechanisms with spinal nociceptive signalling, we decided to investigate HDAC2 expression in the dorsal horn after peripheral injury. Using immunohistochemistry, we found that spinal HDAC2 was mainly seen in neurones and astrocytes, with neuronal expression in naïve tissue 2.6 times greater than that in astrocytes. Cystein (S)-nitrosylation of HDAC2 releases HDAC2 gene silencing and is controlled by nitric oxide (NO). 48 h after intraplantar injection of complete Freund's adjuvant (CFA), there was an ipsilateral increase of the most important NO producing enzyme in pain states, nitric oxide synthase (nNOS), accompanied by an increase in HDAC2 S-nitrosylation. Moreover, a subset of nNOS positive neurones expressed cFos, a known target of HDAC2, suggesting that de-repression of cFos expression following HDAC2 S-nitrosylation might occur after noxious stimulation. We saw no change in global HDAC2 expression in both short and long term pain states. However, HDAC2 was increased in astrocytes 7 days after neuropathic injury suggesting that HDAC2 might inhibit astrocytic gene expression in neuropathic pain states. All together our results indicate that the epigenetic regulation of transcriptional programs in the dorsal horn after injury is cell specific. Moreover, the prominent role of NO in persistent pain states suggests that HDAC2 S-nitrosylation could play a crucial role in the regulation of gene expression leading to hypersensitivity. This article is protected by copyright. All rights reserved.

Type: Article
Title: Complex regulation of the regulator of synaptic plasticity histone deacetylase 2 in the rodent dorsal horn after peripheral injury
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/jnc.13621
Publisher version: http://dx.doi.org/10.1111/jnc.13621
Language: English
Additional information: Copyright © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Epigenetic, HDAC2, astrocyte, nNOS, nitrosylation, pain
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1478135
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