DNA microarray analysis of cannabinoid signaling in mouse brain in vivo

Sophie Parmentier-Batteur, Kunlin Jin, Lin Xie, Xiao Ou Mao, David A. Greenberg

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

To identify novel genes involved in cannabinoid receptor-mediated signaling, we used cDNA microarrays to detect changes in mRNA expression in the forebrains of mice 12 h after they were given a single intraperitoneal dose of the naturally-occurring Cannabis sativa alkaloid Δ9-tetrahydro-cannabinol (Δ9-THC) or the synthetic cannabinoid receptor agonist (R)-(+)-2,3-dihydro-5-methyl-3-[(morpholinyl)methyl] pyrrolo[1,2,3-de]-1,4-benzoxazin-yl-1-naphtalenylmethanone mesylate [R(+)-WIN 55,212-2]. Of ∼11,000 genes from a mouse brain cDNA library that were probed, 65 showed altered (increased or decreased at least 2-fold) expression after exposure to Δ9-THC, 41 after exposure to R(+)-WIN 55,212-2, and 20 genes after exposure to both drugs. Genes affected similarly by Δ9-THC and R(+)-WIN 55,212-2 were considered likely to reflect cannabinoid receptor activation, and expression of the protein products of two such genes not previously implicated in cannabinoid signaling-melanocyte-specific gene-related gene 1 (MRG1) and hexokinase 4 (glucokinase, GK)-was measured by Western blotting and immunohistochemistry. Western blots showed ∼2-fold increases in the levels of both proteins in mouse forebrain. Immunohistochemistry revealed preferential localization of MRG1 to cerebral blood vessels and of GK to hypothalamic neurons. These findings suggest that MRG1 and GK are cannabinoid-regulated genes and that they may be involved in the vascular and hypothalamic effects of cannabinoids, respectively.

Original languageEnglish
Pages (from-to)828-835
Number of pages8
JournalMolecular Pharmacology
Volume62
Issue number4
DOIs
StatePublished - Oct 2002

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