Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region
Abstract The non-euphorigenic phytocannabinoid cannabidiol (CBD) has been used successfully to treat childhood-onset epilepsies. These conditions are associated with developmental delays that often include vocal learning. Zebra finch song, like language, is a complex behavior learned during a sensit...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-34924-z |
| _version_ | 1797822920281554944 |
|---|---|
| author | Mark Tripson Karen Litwa Ken Soderstrom |
| author_facet | Mark Tripson Karen Litwa Ken Soderstrom |
| author_sort | Mark Tripson |
| collection | DOAJ |
| description | Abstract The non-euphorigenic phytocannabinoid cannabidiol (CBD) has been used successfully to treat childhood-onset epilepsies. These conditions are associated with developmental delays that often include vocal learning. Zebra finch song, like language, is a complex behavior learned during a sensitive period of development. Song quality is maintained through continuous sensorimotor refinement involving circuits that control learning and production. Within the vocal motor circuit, HVC is a cortical-like region that when partially lesioned temporarily disrupts song structure. We previously found CBD (10 mg/kg/day) improves post-lesion vocal recovery. The present studies were done to begin to understand mechanisms possibly responsible for CBD vocal protection. We found CBD markedly reduced expression of inflammatory mediators and oxidative stress markers. These effects were associated with regionally-reduced expression of the microglial marker TMEM119. As microglia are key regulators of synaptic reorganization, we measured synapse densities, finding significant lesion-induced circuit-wide decreases that were largely reversed by CBD. Synaptic protection was accompanied by NRF2 activation and BDNF/ARC/ARG3.1/MSK1 expression implicating mechanisms important to song circuit node mitigation of oxidative stress and promotion of synaptic homeostasis. Our findings demonstrate that CBD promotes an array of neuroprotective processes consistent with modulation of multiple cell signaling systems, and suggest these mechanisms are important to post-lesion recovery of a complex learned behavior. |
| first_indexed | 2024-03-13T10:16:22Z |
| format | Article |
| id | doaj.art-ff16c8574d1440fcb874115a9d9d3d04 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-13T10:16:22Z |
| publishDate | 2023-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ff16c8574d1440fcb874115a9d9d3d042023-05-21T11:14:21ZengNature PortfolioScientific Reports2045-23222023-05-0113111810.1038/s41598-023-34924-zCannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like regionMark Tripson0Karen Litwa1Ken Soderstrom2Department of Pharmacology and Toxicology, Brody School of Medicine at East Carolina UniversityDepartment of Anatomy and Cell Biology, Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina UniversityDepartment of Pharmacology and Toxicology, Brody School of Medicine at East Carolina UniversityAbstract The non-euphorigenic phytocannabinoid cannabidiol (CBD) has been used successfully to treat childhood-onset epilepsies. These conditions are associated with developmental delays that often include vocal learning. Zebra finch song, like language, is a complex behavior learned during a sensitive period of development. Song quality is maintained through continuous sensorimotor refinement involving circuits that control learning and production. Within the vocal motor circuit, HVC is a cortical-like region that when partially lesioned temporarily disrupts song structure. We previously found CBD (10 mg/kg/day) improves post-lesion vocal recovery. The present studies were done to begin to understand mechanisms possibly responsible for CBD vocal protection. We found CBD markedly reduced expression of inflammatory mediators and oxidative stress markers. These effects were associated with regionally-reduced expression of the microglial marker TMEM119. As microglia are key regulators of synaptic reorganization, we measured synapse densities, finding significant lesion-induced circuit-wide decreases that were largely reversed by CBD. Synaptic protection was accompanied by NRF2 activation and BDNF/ARC/ARG3.1/MSK1 expression implicating mechanisms important to song circuit node mitigation of oxidative stress and promotion of synaptic homeostasis. Our findings demonstrate that CBD promotes an array of neuroprotective processes consistent with modulation of multiple cell signaling systems, and suggest these mechanisms are important to post-lesion recovery of a complex learned behavior.https://doi.org/10.1038/s41598-023-34924-z |
| spellingShingle | Mark Tripson Karen Litwa Ken Soderstrom Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region Scientific Reports |
| title | Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region |
| title_full | Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region |
| title_fullStr | Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region |
| title_full_unstemmed | Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region |
| title_short | Cannabidiol inhibits neuroinflammatory responses and circuit-associated synaptic loss following damage to a songbird vocal pre-motor cortical-like region |
| title_sort | cannabidiol inhibits neuroinflammatory responses and circuit associated synaptic loss following damage to a songbird vocal pre motor cortical like region |
| url | https://doi.org/10.1038/s41598-023-34924-z |
| work_keys_str_mv | AT marktripson cannabidiolinhibitsneuroinflammatoryresponsesandcircuitassociatedsynapticlossfollowingdamagetoasongbirdvocalpremotorcorticallikeregion AT karenlitwa cannabidiolinhibitsneuroinflammatoryresponsesandcircuitassociatedsynapticlossfollowingdamagetoasongbirdvocalpremotorcorticallikeregion AT kensoderstrom cannabidiolinhibitsneuroinflammatoryresponsesandcircuitassociatedsynapticlossfollowingdamagetoasongbirdvocalpremotorcorticallikeregion |