Neuronal Expression of CB2 Cannabinoid Receptor mRNAs in the Mouse Hippocampus.

In the brain, CB1 cannabinoid receptors primarily mediate the effects of cannabinoids, but CB2 cannabinoid receptors have recently been discovered in the nervous system and also implicated in neuromodulatory roles. To understand the mechanisms of CB2 receptor functions in the brain, it is essential to localize CB2 receptors, but the types of cells expressing CB2 receptors have been controversial. Unequivocal localization of CB2 cannabinoid receptors in the brain has been impeded in part by the low expression levels of CB2 receptors and poor specificity of detection methods. Here, we used an ultrasensitive and specific in situ hybridization method called the RNAscope to determine the spatial pattern of CB2 receptor mRNA expression in the mouse hippocampus. CB2 receptor mRNAs were mostly expressed in a subset of excitatory and inhibitory neurons in the CA1, CA3 and dentate gyrus areas, but rarely in microglia. CB2 receptor knock-out mice were used as a negative control. Using the quantitative real-time PCR, we also found that the temporal pattern of CB2 receptor mRNA expression was stable during postnatal development. Consistent with previous reports, the immunological detection of CB2 receptors was not reliable, implying extremely low levels of the protein expression and/or insufficient specificity of the current anti-CB2 receptor antibodies. Our findings of the expression patterns of CB2 receptor mRNAs may help determine the cell types involved in, and hence the mechanisms of, the CB2 receptor-mediated neuromodulation.
Copyright © 2015. Published by Elsevier Ltd.