Cortical glutamic acid decarboxylase 67 deficiency results in lower cannabinoid 1 receptor messenger RNA expression: Implications for schizophrenia
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, GAD67, and diacylglycerol lipase alpha (the synthesizing enzyme for the endocannabinoid 2-arachidonoylglycerol) mRNA levels in the medial prefrontal cortex of genetically engineered GAD67 heterozygous (GAD67+/-), CB1R heterozygous (CB1R+/-), CB1R knockout (CB1R-/-), and matched wild-type mice. In GAD67+/- mice, GAD67 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 GAD67 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.

Eggan SM,

Lazarus MS,

Stoyak SR,

Volk DW,

Glausier JR,

Huang ZJ,

Lewis DA

Biological Psychiatry

  71 (2): 114-119; Jan 2012

[Abstract]

[DOI]

Investigation of acquired resistance to EGFR-targeted therapies in lung cancer using cDNA microarrays
Abstract: Clinical tools to accurately describe, evaluate, and predict an individuals response to cancer therapy are a field-wide priority; in many advanced cancers, only 10-20% of individuals will have a clinical benefit from therapy, yet we treat the entire population. Furthermore, many therapies are initially effective, but lose effectiveness over time. Here we describe methods to derive in vitro models of resistance to EGFR tyrosine kinase inhibitors. We additionally describe approaches to characterize possible mechanisms of resistance by genomic and transcriptomic approaches. © 2012 Springer Science+Business Media, LLC.

Kani K,

Sordella R,

Mallick P

Methods in Molecular Biology

  795 (2012): 233-253; 2012

[Abstract]

[DOI]