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.
This project will apply the new Ribotag technology to measure the transcriptional and translational changes in excitatory neurons after delta-9-tetrahydrocannabinol (THC) exposure, thereby indicating any molecular and cellular changes that may be effected by cannabis/cannabinoid on developing brain.
| Sulzer, David; Cragg, Stephanie J; Rice, Margaret E (2016) Striatal dopamine neurotransmission: regulation of release and uptake. Basal Ganglia 6:123-148 |
