Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors
Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood–brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic c...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2013-11-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113001939 |
| _version_ | 1818337262829568000 |
|---|---|
| author | M. Mecha A. Feliú P.M. Iñigo L. Mestre F.J. Carrillo-Salinas C. Guaza |
| author_facet | M. Mecha A. Feliú P.M. Iñigo L. Mestre F.J. Carrillo-Salinas C. Guaza |
| author_sort | M. Mecha |
| collection | DOAJ |
| description | Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood–brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component. |
| first_indexed | 2024-12-13T14:52:26Z |
| format | Article |
| id | doaj.art-41e0fc32724248e6bd03babe9b39f8f7 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T14:52:26Z |
| publishDate | 2013-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-41e0fc32724248e6bd03babe9b39f8f72022-12-21T23:41:18ZengElsevierNeurobiology of Disease1095-953X2013-11-0159141150Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptorsM. Mecha0A. Feliú1P.M. Iñigo2L. Mestre3F.J. Carrillo-Salinas4C. Guaza5Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, SpainDepartment of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, SpainDepartment of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, SpainDepartment of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, SpainDepartment of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, SpainCorresponding author at: Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Avda. Dr. Arce 37, 28002, Madrid, Spain. Fax: +34 915854754.; Department of Functional and Systems Neurobiology, Neuroimmunology Group, Cajal Institute, CSIC, Madrid, SpainInflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood–brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties. Yet, how this compound modifies the deleterious effects of inflammation in TMEV-induced demyelinating disease (TMEV-IDD) remains unknown. Using this viral model of multiple sclerosis (MS), we demonstrate that CBD decreases the transmigration of blood leukocytes by downregulating the expression of vascular cell adhesion molecule-1 (VCAM-1), chemokines (CCL2 and CCL5) and the proinflammatory cytokine IL-1β, as well as by attenuating the activation of microglia. Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD, as the A2A antagonist ZM241385 partially blocks the protective effects of CBD in the initial stages of inflammation. Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component.http://www.sciencedirect.com/science/article/pii/S0969996113001939CannabidiolMultiple sclerosisInflammationVCAM-1ChemokinesTheiler's murine encephalomyelitis virus |
| spellingShingle | M. Mecha A. Feliú P.M. Iñigo L. Mestre F.J. Carrillo-Salinas C. Guaza Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors Neurobiology of Disease Cannabidiol Multiple sclerosis Inflammation VCAM-1 Chemokines Theiler's murine encephalomyelitis virus |
| title | Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors |
| title_full | Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors |
| title_fullStr | Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors |
| title_full_unstemmed | Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors |
| title_short | Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors |
| title_sort | cannabidiol provides long lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis a role for a2a receptors |
| topic | Cannabidiol Multiple sclerosis Inflammation VCAM-1 Chemokines Theiler's murine encephalomyelitis virus |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113001939 |
| work_keys_str_mv | AT mmecha cannabidiolprovideslonglastingprotectionagainstthedeleteriouseffectsofinflammationinaviralmodelofmultiplesclerosisarolefora2areceptors AT afeliu cannabidiolprovideslonglastingprotectionagainstthedeleteriouseffectsofinflammationinaviralmodelofmultiplesclerosisarolefora2areceptors AT pminigo cannabidiolprovideslonglastingprotectionagainstthedeleteriouseffectsofinflammationinaviralmodelofmultiplesclerosisarolefora2areceptors AT lmestre cannabidiolprovideslonglastingprotectionagainstthedeleteriouseffectsofinflammationinaviralmodelofmultiplesclerosisarolefora2areceptors AT fjcarrillosalinas cannabidiolprovideslonglastingprotectionagainstthedeleteriouseffectsofinflammationinaviralmodelofmultiplesclerosisarolefora2areceptors AT cguaza cannabidiolprovideslonglastingprotectionagainstthedeleteriouseffectsofinflammationinaviralmodelofmultiplesclerosisarolefora2areceptors |