Rapid ReportNeuron-restrictive silencer factor causes epigenetic silencing of Kv4.3 gene after peripheral nerve injury
Section snippets
Animals and surgery
Male C57BL/6J mice weighing 20–25 g were used. They were kept in a room with a temperature of 21±2 °C with free access to standard laboratory diet and tap water. The experiments were designed to minimize the number of animals used and their suffering. All procedures were approved by the Nagasaki University Animal Care Committee and were carried out in accordance with the National Institute of Health Guide for the Care and Use of Laboratory Animals. Partial sciatic nerve ligation was performed
Results
To examine whether Kv4.3 is downregulated at the transcriptional level after injury, we quantified its mRNA expressions in the DRG by real-time PCR. There was a significant reduction in Kv4.3 expression starting from day 7 post-injury, which persisted at least 14 days (Fig. 1A). Using TFSEARCH program (version 1.3, available at: http://www.cbrc.jp/research/db/TFSEARCHJ.html), we found that mouse Kv4.3 gene contains a putative NRSE sequence within intron 2, which is completely conserved in rat (
Discussion
Given that the long-term changes in pain-related gene expression underlie the most important mechanisms responsible for injury-induced neuropathic pain (Hökfelt et al., 2006, Ueda, 2006), we focused on the critical contribution of epigenetic mechanisms (Borrelli et al., 2008). Here, we demonstrated that injury-induced Kv4.3 downregulation, which is implicated in neuronal hyperexcitability underlying neuropathic pain (Kim et al., 2002, Chien et al., 2007), is closely related to the
Conclusion
In conclusion, the present study demonstrated that NRSF plays a key role in injury-induced Kv4.3 downregulation in the DRG through epigenetic mechanisms. A study concerning the regulatory mechanisms for NRSE-NRSF system after injury is the next subject for research.
Acknowledgments
We thank W. Xie for technical help. This work was supported by MEXT KAKENHI (17109015 to Hiroshi Ueda). Health Sciences Research Grants from the Ministry of Health, Labor and Welfare of Japan (Hiroshi Ueda) and Health Labour Sciences Research Grant “Third Term Comprehensive Control Research for Cancer” (398-49) are also supported this work.
References (19)
- et al.
Epigenetic targets of HDAC inhibition in neurodegenerative and psychiatric disorders
Curr Opin Pharmacol
(2008) - et al.
The many faces of REST oversee epigenetic programming of neuronal genes
Curr Opin Neurobiol
(2005) - et al.
Decoding the epigenetic language of neuronal plasticity
Neuron
(2008) - et al.
Intrathecal morphine in mice: a new technique
Eur J Pharmacol
(1980) - et al.
Downregulation of voltage-gated potassium channel alpha gene expression in dorsal root ganglia following chronic constriction injury of the rat sciatic nerve
Brain Res Mol Brain Res
(2002) - et al.
A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells
Neuron
(1992) - et al.
Profiling of BoNT/C3-reversible gene expression induced by lysophosphatidic acid: ephrinB1 gene up-regulation underlying neuropathic hyperalgesia and allodynia
Neurochem Int
(2009) Molecular mechanisms of neuropathic pain-phenotypic switch and initiation mechanisms
Pharmacol Ther
(2006)- et al.
The cell and molecular basis of mechanical, cold, and inflammatory pain
Science
(2008)
Cited by (0)
- 1
These authors have contributed equally to this manuscript.