A single acute pharmacological dose of gamma-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex

作者:Kemmel Veronique*; Klein Christian; Dembele Doulaye; Jost Bernard; Taleb Omar; Aunis Dominique; Mensah Nyagan Ayikoe G; Maitre Michel
来源:Physiological Genomics, 2010, 41(2): 146-160.
DOI:10.1152/physiolgenomics.00208.2009

摘要

Kemmel V, Klein C, Dembele D, Jost B, Taleb O, Aunis D, Mensah-Nyagan AG, Maitre M. A single acute pharmacological dose of gamma-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex. Physiol Genomics 41: 146-160, 2010. First published January 26, 2010; doi: 10.1152/physiolgenomics.00208.2009.-gamma-Hydroxybutyrate (GHB) is a natural brain neuromodulator that has its own enzymatic machinery for synthesis and degradation, release, and transport systems and several receptors that belong to the G protein-coupled receptor (GPCR) family. Targeting of this system with exogenous GHB is used in therapy to induce sleep and anesthesia and to reduce alcohol withdrawal syndrome. GHB is also popular as a recreational drug for its anxiolytic and mild euphoric effects. However, in both cases, GHB must be administered at high doses in order to maintain GHB concentrations in brain of similar to 800-1,000 mu M. These high concentrations are thought to be necessary for interactions with low-affinity sites on GABAB(B) receptor, but the molecular targets and cellular mechanisms modulated by GHB remain poorly characterized. Therefore, to provide new insights into the elucidation of GHB mechanisms of action and open new tracks for future investigations, we explored changes of GHB-induced transcriptomes in rat hippocampus and prefrontal cortex by using DNA microarray studies. We demonstrate that a single acute anesthetic dose of 1 g/kg GHB alters a large number of genes, 121 in hippocampus and 53 in prefrontal cortex; 16 genes were modified simultaneously in both brain regions. In terms of molecular functions, the majority of modified genes coded for proteins or nucleotide binding sites. In terms of Gene Ontology (GO) functional categories, the largest groups were involved in metabolic processing for hippocampal genes and in biological regulation for prefrontal cortex genes. The majority of genes modified in both structures were implicated in cell communication processes. Western blot and immunohistochemical studies carried out on eight selected proteins confirmed the microarray findings.

  • 出版日期2010-4