Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: Implications for schizophrenia

Eggan, S. M., Lazarus, M. S., Stoyak, S. R., Volk, D. W., Glausier, J. R., Huang, Z. J., Lewis, D. A. (2012) Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: Implications for schizophrenia. Biological Psychiatry, 71 (2). pp. 114-119. ISSN 00063223 (ISSN)

URL: http://www.ncbi.nlm.nih.gov/pubmed/22036037
DOI: 10.1016/j.biopsych.2011.09.014

Abstract

Levels of cannabinoid 1 receptor (CB1R) messenger RNA (mRNA) and protein, which are expressed most heavily in the cholecystokinin class of γ-aminobutyric acid (GABA) neurons, are lower in the dorsolateral prefrontal cortex in schizophrenia, and the magnitude of these differences is strongly correlated with that for glutamic acid decarboxylase 67 (GAD 67) mRNA, a synthesizing enzyme for GABA. However, whether this correlation reflects a cause-effect relationship is unknown. Using quantitative in situ hybridization, we measured CB1R, GAD 67, and diacylglycerol lipase alpha (the synthesizing enzyme for the endocannabinoid 2-arachidonoylglycerol) mRNA levels in the medial prefrontal cortex of genetically engineered GAD 67 heterozygous (GAD 67 +/-), CB1R heterozygous (CB1R +/-), CB1R knockout (CB1R -/-), and matched wild-type mice. In GAD 67 +/- mice, GAD 67 and CB1R mRNA levels were significantly reduced by 37% and 16%, respectively, relative to wild-type mice and were significantly correlated across animals (r =.61; p =.01). In contrast, GAD 67 mRNA levels were unaltered in CB1R +/- andCB1R -/- mice. Expression of diacylglycerol lipase alpha mRNA, which is not altered in schizophrenia, was also not altered in any of the genetically engineered mice. The findings that reduced GAD 67 mRNA expression can induce lower CB1R mRNA expression support the hypothesis that lower cortical levels of CB1Rs in schizophrenia may partially compensate for deficient GAD 67-mediated GABA synthesis by reducing endogenous cannabinoid suppression of GABA release. © 2012 Society of Biological Psychiatry.

Item Type: Paper
Uncontrolled Keywords: Cannabis cholecystokinin cognition GABA in situ hybridization interneurons mouse model working memory 2 arachidonoylglycerol cannabinoid 1 receptor diacylglycerol lipase alpha glutamate decarboxylase 67 lipoprotein lipase messenger RNA unclassified drug animal experiment article brain region female gene expression male mouse nonhuman nucleotide sequence prefrontal cortex priority journal schizophrenia
Subjects: bioinformatics > genomics and proteomics > small molecules > GABAergic
diseases & disorders > mental disorders > schizophrenia
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mRNA dynamics
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: CSHL Librarian
Date Deposited: 11 Apr 2012 16:24
Last Modified: 10 May 2013 14:59
PMCID: PMC3237751
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25793

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