Effects of Cannabis on Neuronal Translation

 描述(申请人提供)：这项研究旨在确定在发育过程中暴露于大麻/大麻类药物时兴奋性神经元的分子变化。为此，将分析在青春期期间使用德尔塔-9-四氢大麻酚(THC)治疗后转录和翻译的变化。通过将RiboTag小鼠与神经元特异性CaMKIIa-Cre小鼠杂交，我们将在兴奋性神经元中特异性地表达HA标记的核糖体。纯化的多聚体结合的mRNAs将通过深度测序进行分析，以进行mRNA丰度的转录分析，或通过核糖体图谱进行翻译的定量分析。这项研究的结果将包括因大麻暴露而上调和下调的丰富基因集。本研究开发的实验方法将在未来用于确定大麻在大脑发育的不同阶段的影响，以及这些影响与早期神经发育变化的相关性，包括神经发生、神经迁移、神经元和神经胶质分化和神经元成熟。分子图谱还将用于测试靶向mTOR信号的效果，以此作为减轻大麻潜在有害影响的手段。

 DESCRIPTION (provided by applicant): This study is intended to identify molecular changes in excitatory neurons upon cannabis/cannabinoid exposure during development. To this end, transcriptional and translational changes will be analyzed after treatment with delta-9-tetrahydrocannabinol (THC) during peri-adolescence. By crossing the RiboTag mice to the neuronal specific CaMKIIa-Cre mice, we will specifically express HA-tagged ribosomes in excitatory neurons. Purified polysome-bound mRNAs will be analyzed by deep sequencing for transcriptional analysis of mRNA abundance or ribosomal profiling for quantitative analysis of translation. The results of this study will include enriched gene sets that are up- and down-regulated by cannabis exposure. The experimental methods developed in this study will be used in the future to determine the effects of cannabis during different stages of brain development, and how these effects correlate with the early neurodevelopmental changes including neurogenesis, neural migration, and neuronal and glial differentiation and neuronal maturation. The molecular profiles will also be used to test the effects of targeting mTOR signaling as a means to mitigate potentially harmful effects of cannabis.