| Autor: |
Li H; iHuman Institute, ShanghaiTech University, Shanghai 201210, China., Ye Q; High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui 230031, China., Wang D; iHuman Institute, ShanghaiTech University, Shanghai 201210, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Shi B; iHuman Institute, ShanghaiTech University, Shanghai 201210, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Xu W; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai 200433, China., Zhang S; iHuman Institute, ShanghaiTech University, Shanghai 201210, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China., Han X; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai 200433, China., Zhang XY; Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China.; Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Ministry of Education, Shanghai 200433, China., Thompson GJ; iHuman Institute, ShanghaiTech University, Shanghai 201210, China. |
| Abstrakt: |
The cannabinoid receptor 1 (CB 1 ) is famous as the target of Δ 9 -tetrahydrocannabinol (THC), which is the active ingredient of marijuana. Suppression of CB 1 is frequently suggested as a drug target or gene therapy for many conditions (e.g., obesity, Parkinson's disease). However, brain networks affected by CB 1 remain elusive, and unanticipated psychological effects in a clinical trial had dire consequences. To better understand the whole brain effects of CB 1 suppression we performed in vivo imaging on mice under complete knockout of the gene for CB 1 ( cnr1 -/- ) and also under the CB 1 inverse agonist rimonabant. We examined white matter structural changes and brain function (network activity and directional uniformity) in cnr1 -/- mice. In cnr1 -/- mice, white matter (in both sexes) and functional directional uniformity (in male mice) were altered across the brain but network activity was largely unaltered. Conversely, under rimonabant, functional directional uniformity was not altered but network activity was altered in cortical regions, primarily in networks known to be altered by THC (e.g., neocortex, hippocampal formation). However, rimonabant did not alter many brain regions found in both our cnr1 -/- results and previous behavioral studies of cnr1 -/- mice (e.g., thalamus, infralimbic area). This suggests that chronic loss of cnr1 is substantially different from short-term suppression, subtly rewiring the brain but largely maintaining the network activity. Our results help explain why pathological mutations in CB 1 (e.g., chronic pain) do not always provide insight into the side effects of CB 1 suppression (e.g., clinical depression), and thus urge more preclinical studies for any drugs that suppress CB 1 . |
