Chromatin remodeling is a key mechanism underlying cocaine-induced plasticity in striatum
| Autor: | Hoang Trang Truong, Quincey LaPlant, Nadia M. Tsankova, Arvind Kumar, Kimberly N. Whistler, Teresa S. Sasaki, Rachael L. Neve, David W. Self, David E. H. Theobald, Eric J. Nestler, Scott J. Russo, Kwang H. Choi, William Renthal |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Time Factors Neuroscience(all) Mice Transgenic Striatum Epigenetics of cocaine addiction Motor Activity PC12 Cells Chromatin remodeling Drug Administration Schedule Histone Deacetylases Histones Rats Sprague-Dawley Mice Cocaine Dopamine Uptake Inhibitors Animals Immunoprecipitation Drug Interactions RNA Messenger Enzyme Inhibitors Promoter Regions Genetic Transcription factor Regulation of gene expression Neuronal Plasticity biology Behavior Animal Reverse Transcriptase Polymerase Chain Reaction General Neuroscience Cyclin-dependent kinase 5 Brain-Derived Neurotrophic Factor Gene Transfer Techniques Acetylation Cyclin-Dependent Kinase 5 Chromatin Assembly and Disassembly Immunohistochemistry Corpus Striatum Rats Mice Inbred C57BL Butyrates Protein Subunits Histone Gene Expression Regulation biology.protein Conditioning Operant Histone deacetylase activity Neuroscience Proto-Oncogene Proteins c-fos |
| Zdroj: | Neuron. 48(2) |
| ISSN: | 0896-6273 |
| Popis: | Summary Given that cocaine induces neuroadaptations through regulation of gene expression, we investigated whether chromatin remodeling at specific gene promoters may be a key mechanism. We show that cocaine induces specific histone modifications at different gene promoters in striatum, a major neural substrate for cocaine's behavioral effects. At the cFos promoter, H4 hyperacetylation is seen within 30 min of a single cocaine injection, whereas no histone modifications were seen with chronic cocaine, consistent with cocaine's ability to induce cFos acutely, but not chronically. In contrast, at the BDNF and Cdk5 promoters, genes that are induced by chronic, but not acute, cocaine, H3 hyperacetylation was observed with chronic cocaine only. ΔFosB, a cocaine-induced transcription factor, appears to mediate this regulation of the Cdk5 gene. Furthermore, modulating histone deacetylase activity alters locomotor and rewarding responses to cocaine. Thus, chromatin remodeling is an important regulatory mechanism underlying cocaine-induced neural and behavioral plasticity. |
| Databáze: | OpenAIRE |
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