Open AccessOverexpression of cyclic GMP ‐dependent protein kinase reduces MeCP 2 and HDAC 2 expression
Author(s) -
Deschatrettes Elodie,
Jouvert Peggy,
Zwiller Jean
Publication year - 2012
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.92
Subject(s) - soluble guanylyl cyclase , histone deacetylase , microbiology and biotechnology , protein kinase a , phosphorylation , chemistry , signal transduction , cgmp dependent protein kinase , nitric oxide , biology , endocrinology , histone , biochemistry , cyclin dependent kinase 2 , guanylate cyclase , gene
Nitric oxide ( NO ) and the C ‐type natriuretic peptide ( CNP ) exert their action via stimulation of the cyclic GMP ( cGMP )‐signaling pathway, which includes the activation of cGMP ‐dependent protein kinases ( PKG ). The present report shows that the activation of PKG by local application of 8‐bromo‐ cGMP in the caudate–putamen reduced the expression of the epigenetic markers, methyl‐ CpG ‐binding protein 2 ( MeCP 2) and histone deacetylase 2 ( HDAC 2), in dopaminergic projection areas of cocaine‐treated rats. An effect of lesser amplitude was observed when rats were not injected with cocaine. We also studied the effect of PKG overexpression by injecting a plasmid vector containing the human PKG ‐Iα cDNA in either the caudate–putamen or the ventral tegmental area. Injection in the caudate–putamen reduced the epigenetic parameters with higher amplitude than the cGMP analog. The effect was abolished by the injection of a selective PKG inhibitor, confirming that it was due to PKG ‐dependent phosphorylation. As MeCP 2 and HDAC 2 modulate dynamic functions in the adult brain such as memory formation and synaptic plasticity, the downregulation of expression by PKG suggests that the cGMP pathway affects cognitive processes through a mechanism that comprises the MeCP 2/ HDAC 2 complex and the subsequent control of gene silencing.