Effects of Cannabis on Neuronal Translation

大麻对神经元翻译的影响

• 批准号: 9035835
• 负责人: David Sulzer
• 金额: $ 8万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9035835
• 关键词: AM 251; Absence of pain sensation; Adolescence; Affect; Aftercare; Binding; Brain; CNR1 gene; Cannabinoids; Cannabis; Catalepsy; Development; Experimental Models; FRAP1 gene; Future; Gene Combinations; Genes; Genetic Transcription; Glial Differentiation; Glutamates; Health; Hippocampus (Brain); Lead; Learning; Long-Term Effects; Measures; Memory; Messenger RNA; Methodology; Methods; Molecular; Molecular Profiling; Mus; Neuronal Differentiation; Neurons; Pattern; Polyribosomes; Population; Presynaptic Terminals; Proteins; Ribosomal Proteins; Ribosomes; Role; Signal Transduction; Staging; Stream; Synaptic Transmission; THC exposure; Technology; Testing; Tetrahydrocannabinol; Transcript; Translating; Translation Alteration; Translational Regulation; Translations; brain tissue; cannabinoid receptor; deep sequencing; density; drug of abuse; excitatory neuron; migration; mouse model; natural hypothermia; neurogenesis; postsynaptic neurons; promoter; recombinase; relating to nervous system; ribosome profiling; selective expression; transcriptome; transcriptome sequencing

 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.

 描述（由申请人提供）：本研究旨在确定发育期间大麻/大麻素暴露后兴奋性神经元的分子变化。为此，将在青春期前后用δ-9-四氢大麻酚（THC）治疗后分析转录和翻译变化。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表达HA标记的核糖体。将通过深度测序分析纯化的多核糖体结合的mRNA，用于mRNA丰度的转录分析或用于翻译定量分析的核糖体分析。这项研究的结果将包括通过大麻暴露上调和下调的富集基因集。本研究中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，以及这些影响如何与早期神经发育变化相关，包括神经发生，神经迁移，神经元和神经胶质分化以及神经元成熟。分子特征也将用于测试靶向mTOR信号传导的效果，作为减轻大麻潜在有害影响的手段。