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Complex regulation of the regulator of synaptic plasticity histone deacetylase 2 in the rodent dorsal horn after peripheral injury
Author(s) -
Maiarù Maria,
Morgan Oakley B.,
Tochiki Keri K.,
Hobbiger Eleanor J.,
Rajani Kaveeta,
Overington Dorothy W. U.,
Géranton Sandrine M.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13621
Subject(s) - histone deacetylase , neuropathic pain , microglia , hdac1 , microbiology and biotechnology , neuroscience , dorsal root ganglion , gene silencing , histone , peripheral nerve injury , epigenetics , chemistry , nitric oxide , biology , spinal cord , endocrinology , inflammation , immunology , biochemistry , gene , regeneration (biology)
Histone deacetylases ( HDAC s), HDAC 2 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 the HDAC 2 expression in the dorsal horn after peripheral injury. Using immunohistochemistry, we found that spinal HDAC 2 was mainly seen in neurons and astrocytes, with neuronal expression in naïve tissue 2.6 times greater than that in astrocytes. Cysteine (S)‐nitrosylation of HDAC 2 releases HDAC 2 gene silencing and is controlled by nitric oxide ( NO ). A duration of 48 h after intraplantar injection of complete Freund's adjuvant, there was an ipsilateral increase in the most important NO ‐producing enzyme in pain states, nitric oxide synthase ( nNOS ), accompanied by an increase in HDAC 2 S‐nitrosylation. Moreover, a subset of nNOS ‐positive neurons expressed cF os, a known target of HDAC 2, suggesting that derepression of cF os expression following HDAC 2 S‐nitrosylation might occur after noxious stimulation. We saw no change in global HDAC 2 expression in both short‐ and long‐term pain states. However, HDAC 2 was increased in astrocytes 7 days after neuropathic injury suggesting that HDAC 2 might inhibit astrocytic gene expression in neuropathic pain states. All together, our results indicate that the epigenetic regulation of transcriptional programmes in the dorsal horn after injury is cell specific. Moreover, the prominent role of NO in persistent pain states suggests that HDAC 2 S‐nitrosylation could play a crucial role in the regulation of gene expression leading to hypersensitivity.Our manuscript describes for the first time the regulation of the memory regulator histone deacetylase 2 (HDAC2) in the superficial dorsal horn of adult rats following peripheral injury. Our cell‐specific approach has revealed a complex pattern of expression of spinal HDAC2 that depends on the injury and the cell type, suggesting a sophisticated regulation of gene expression by HDAC2.