Methyl-CpG-binding protein 2 (MeCP2) and the Control of Neuronal Plasticity in Nociceptive Pathways. (360G-Wellcome-085566_Z_08_Z)
Our previously published research suggested that noxious stimulation relieved gene repression by MeCP2, leading to the expression of a number of genes in specific populations of dorsal horn neurons and increased pain sensitivity. This proposal is an investigation of the regulation of persistent pain sensitivity by modulation of MeCP2 activity but is more generally concerned with the role of MeCP2 in the regulation of neuronal plasticity. We will study MeCP2 activity following activation of pai n pathways concentrating on both the phosphorylation of MeCP2 as a mechanism for gene de-repression as well as the inhibition of MeCP2 translation by activity-dependant regulation of microRNA miR-132. We will also study the influence of MeCP2 target genes on persistent pain states and the effects of MeCP2 gene deletion on pain signalling. Specifically, we will investigate the pain phenotype of pre-symptomatic mice that are either MeCP2 male nulls or female heterozygotes . The use of female heterozygotes has the advantage that MeCP2 is deleted in a mosaic fashion throughout the central nervous system allowing us to study the behaviour of adjacent neurons which are either normal or lack MeCP2.
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Grant Details
Amount Awarded | 266332 |
Applicant Surname | Hunt |
Approval Committee | Molecular and Cellular Neuroscience Funding Committee |
Award Date | 2008-09-16T00:00:00+00:00 |
Financial Year | 2007/08 |
Grant Programme: Title | Project Grant |
Internal ID | 085566/Z/08/Z |
Lead Applicant | Prof Stephen Hunt |
Other Applicant(s) | Dr Sandrine Geranton |
Partnership Value | 266332 |
Planned Dates: End Date | 2012-03-31T00:00:00+00:00 |
Planned Dates: Start Date | 2008-10-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Greater London |