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MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway

BACKGROUND: The Methyl CpG binding protein 2 gene (MeCP2 gene) encodes a critical transcriptional repressor and is widely expressed in mammalian neurons. MeCP2 plays a critical role in neuronal differentiation, neural development, and synaptic plasticity. Mutations and duplications of the human MECP...

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Autores principales: Zhang, Ran, Huang, Min, Cao, Zhijuan, Qi, Jieyu, Qiu, Zilong, Chiang, Li-Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404689/
https://www.ncbi.nlm.nih.gov/pubmed/25885346
http://dx.doi.org/10.1186/s12990-015-0015-4
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author Zhang, Ran
Huang, Min
Cao, Zhijuan
Qi, Jieyu
Qiu, Zilong
Chiang, Li-Yang
author_facet Zhang, Ran
Huang, Min
Cao, Zhijuan
Qi, Jieyu
Qiu, Zilong
Chiang, Li-Yang
author_sort Zhang, Ran
collection PubMed
description BACKGROUND: The Methyl CpG binding protein 2 gene (MeCP2 gene) encodes a critical transcriptional repressor and is widely expressed in mammalian neurons. MeCP2 plays a critical role in neuronal differentiation, neural development, and synaptic plasticity. Mutations and duplications of the human MECP2 gene lead to severe neurodevelopmental disorders, such as Rett syndrome and autism. In this study we investigate the role of MeCP2 in the spinal cord and found that MeCP2 plays an important role as an analgesic mediator in pain circuitry. FINDINGS: Experiments using MeCP2 transgenic mice showed that overexpression of MeCP2 weakens both acute mechanical pain and thermal pain, suggesting an analgesic role of MeCP2 in acute pain transduction. We found that through p-CREB/miR-132 signaling cascade is involved in MeCP2-mediated pain transduction. We also examined the role of MeCP2 in chronic pain formation using spared nerve injury (SNI) model. Strikingly, we found that development of neuropathic pain attenuates in MeCP2 transgenic mice comparing to wild type (WT) mice. CONCLUSIONS: Our study shows that MeCP2 plays an analgesic role in both acute pain transduction and chronic pain formation through regulating CREB-miR-132 pathway. This work provides a potential therapeutic target for neural pathologic pain, and also sheds new lights on the abnormal sensory mechanisms associated with autism spectrum orders.
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spelling pubmed-44046892015-04-22 MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway Zhang, Ran Huang, Min Cao, Zhijuan Qi, Jieyu Qiu, Zilong Chiang, Li-Yang Mol Pain Short Report BACKGROUND: The Methyl CpG binding protein 2 gene (MeCP2 gene) encodes a critical transcriptional repressor and is widely expressed in mammalian neurons. MeCP2 plays a critical role in neuronal differentiation, neural development, and synaptic plasticity. Mutations and duplications of the human MECP2 gene lead to severe neurodevelopmental disorders, such as Rett syndrome and autism. In this study we investigate the role of MeCP2 in the spinal cord and found that MeCP2 plays an important role as an analgesic mediator in pain circuitry. FINDINGS: Experiments using MeCP2 transgenic mice showed that overexpression of MeCP2 weakens both acute mechanical pain and thermal pain, suggesting an analgesic role of MeCP2 in acute pain transduction. We found that through p-CREB/miR-132 signaling cascade is involved in MeCP2-mediated pain transduction. We also examined the role of MeCP2 in chronic pain formation using spared nerve injury (SNI) model. Strikingly, we found that development of neuropathic pain attenuates in MeCP2 transgenic mice comparing to wild type (WT) mice. CONCLUSIONS: Our study shows that MeCP2 plays an analgesic role in both acute pain transduction and chronic pain formation through regulating CREB-miR-132 pathway. This work provides a potential therapeutic target for neural pathologic pain, and also sheds new lights on the abnormal sensory mechanisms associated with autism spectrum orders. BioMed Central 2015-04-12 /pmc/articles/PMC4404689/ /pubmed/25885346 http://dx.doi.org/10.1186/s12990-015-0015-4 Text en © Zhang et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Short Report
Zhang, Ran
Huang, Min
Cao, Zhijuan
Qi, Jieyu
Qiu, Zilong
Chiang, Li-Yang
MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway
title MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway
title_full MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway
title_fullStr MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway
title_full_unstemmed MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway
title_short MeCP2 plays an analgesic role in pain transmission through regulating CREB / miR-132 pathway
title_sort mecp2 plays an analgesic role in pain transmission through regulating creb / mir-132 pathway
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404689/
https://www.ncbi.nlm.nih.gov/pubmed/25885346
http://dx.doi.org/10.1186/s12990-015-0015-4
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