Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease
The present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). MPTP...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Journal of Immunology Research |
| Online Access: | http://dx.doi.org/10.1155/2020/5093493 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849306931519291392 |
|---|---|
| author | Rayul Wi Young Cheul Chung Byung Kwan Jin |
| author_facet | Rayul Wi Young Cheul Chung Byung Kwan Jin |
| author_sort | Rayul Wi |
| collection | DOAJ |
| description | The present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). MPTP induced a significant loss of nigrostriatal dopamine neurons and glial activation in the substantia nigra (SN) and striatum (STR) as visualized by tyrosine hydroxylase (TH) or macrophage antigen complex-1 (MAC-1) or glial fibrillary acidic protein (GFAP) immunocytochemistry, respectively. RT-PCR analysis shows the upregulation of inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α in microglia in the SN in vivo, indicating the activation of the inflammatory system. By contrast, treatment with capsaicin (a specific TRPV1 agonist) increased the survival of dopamine neurons in the SN and their fibers and dopamine levels in the STR in MPTP mice. Capsaicin neuroprotection is accompanied by inhibiting MPTP-induced glial activation and production of inflammatory cytokines. Treatment with AM251 and AM630 (CB1/2 antagonists) abolished capsaicin-induced beneficial effects, indicating the existence of a functional crosstalk between CB and TRPV1. Moreover, treatment with anandamide (an endogenous agonist for both CB and TRVP1) rescued nigrostriatal dopamine neurons and reduced gliosis-derived neuroinflammatory responses in MPTP mice. These results suggest that the cannabinoid and vanilloid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with neuroinflammation. |
| format | Article |
| id | doaj-art-24bf2883f6434c9e800bb4df274d2c85 |
| institution | Kabale University |
| issn | 2314-8861 2314-7156 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Immunology Research |
| spelling | doaj-art-24bf2883f6434c9e800bb4df274d2c852025-08-20T03:54:56ZengWileyJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/50934935093493Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s DiseaseRayul Wi0Young Cheul Chung1Byung Kwan Jin2Department of Neuroscience, Graduate School, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Biochemistry & Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaDepartment of Neuroscience, Graduate School, School of Medicine, Kyung Hee University, Seoul 02447, Republic of KoreaThe present study examined whether crosstalk between cannabinoid (CB) and transient potential receptor vanilloid type 1 (TRPV1) could contribute to the survival of nigrostriatal dopamine neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease (PD). MPTP induced a significant loss of nigrostriatal dopamine neurons and glial activation in the substantia nigra (SN) and striatum (STR) as visualized by tyrosine hydroxylase (TH) or macrophage antigen complex-1 (MAC-1) or glial fibrillary acidic protein (GFAP) immunocytochemistry, respectively. RT-PCR analysis shows the upregulation of inducible nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α in microglia in the SN in vivo, indicating the activation of the inflammatory system. By contrast, treatment with capsaicin (a specific TRPV1 agonist) increased the survival of dopamine neurons in the SN and their fibers and dopamine levels in the STR in MPTP mice. Capsaicin neuroprotection is accompanied by inhibiting MPTP-induced glial activation and production of inflammatory cytokines. Treatment with AM251 and AM630 (CB1/2 antagonists) abolished capsaicin-induced beneficial effects, indicating the existence of a functional crosstalk between CB and TRPV1. Moreover, treatment with anandamide (an endogenous agonist for both CB and TRVP1) rescued nigrostriatal dopamine neurons and reduced gliosis-derived neuroinflammatory responses in MPTP mice. These results suggest that the cannabinoid and vanilloid system may be beneficial for the treatment of neurodegenerative diseases, such as PD, that are associated with neuroinflammation.http://dx.doi.org/10.1155/2020/5093493 |
| spellingShingle | Rayul Wi Young Cheul Chung Byung Kwan Jin Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease Journal of Immunology Research |
| title | Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease |
| title_full | Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease |
| title_fullStr | Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease |
| title_full_unstemmed | Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease |
| title_short | Functional Crosstalk between CB and TRPV1 Receptors Protects Nigrostriatal Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease |
| title_sort | functional crosstalk between cb and trpv1 receptors protects nigrostriatal dopaminergic neurons in the mptp model of parkinson s disease |
| url | http://dx.doi.org/10.1155/2020/5093493 |
| work_keys_str_mv | AT rayulwi functionalcrosstalkbetweencbandtrpv1receptorsprotectsnigrostriataldopaminergicneuronsinthemptpmodelofparkinsonsdisease AT youngcheulchung functionalcrosstalkbetweencbandtrpv1receptorsprotectsnigrostriataldopaminergicneuronsinthemptpmodelofparkinsonsdisease AT byungkwanjin functionalcrosstalkbetweencbandtrpv1receptorsprotectsnigrostriataldopaminergicneuronsinthemptpmodelofparkinsonsdisease |