| Full text | |
| Author(s): |
dos Santos Pereira, Mauricio
[1, 2, 3, 4]
;
Abreu, Gabriel Henrique Dias
[1, 3]
;
Rocca, Jeremy
[2]
;
Hamadat, Sabah
[2]
;
Raisman-Vozari, Rita
[2]
;
Michel, Patrick Pierre
[2]
;
Del Bel, Elaine
[1, 3, 4]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Sao Paulo - Brazil
[2] Sorbonne Univ UM75, Paris Brain Inst, Inserm U 1127, CNRS UMR 7225, Paris - France
[3] Univ Sao Paulo, FORP, Dept Basic & Oral Biol, Campus USP, Ribeirao Preto - Brazil
[4] Univ Sao Paulo, FMRP, Dept Physiol, Campus USP, Ribeirao Preto - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | FRONTIERS IN PHARMACOLOGY; v. 11, JAN 11 2021. |
| Web of Science Citations: | 0 |
| Abstract | |
Our present objective was to better characterize the mechanisms that regulate striatal neuroinflammation in mice developing L-DOPA-induced dyskinesia (LID). For that, we used 6-hydroxydopamine (6-OHDA)-lesioned mice rendered dyskinetic by repeated intraperitoneal injections of 3,4-dihydroxyphenyl-L-alanine (L-DOPA) and quantified ensuing neuroinflammatory changes in the dopamine-denervated dorsal striatum. LID development was associated with a prominent astrocytic response, and a more moderate microglial cell reaction restricted to this striatal area. The glial response was associated with elevations in two pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta. Treatment with the phytocannabinoid cannabidiol and the transient receptor potential vanilloid-1 (TRPV-1) channel antagonist capsazepine diminished LID intensity and decreased TNF-alpha levels without impacting other inflammation markers. To possibly reproduce the neuroinflammatory component of LID, we exposed astrocyte and microglial cells in culture to candidate molecules that might operate as inflammatory cues during LID development, i.e., L-DOPA, dopamine, or glutamate. Neither L-DOPA nor dopamine produced an inflammatory response in glial cell cultures. However, glutamate enhanced TNF-alpha secretion and GFAP expression in astrocyte cultures and promoted Iba-1 expression in microglial cultures. Of interest, the antidyskinetic treatment with cannabidiol + capsazepine reduced TNF-alpha release in glutamate-activated astrocytes. TNF-alpha, on its own, promoted the synaptic release of glutamate in cortical neuronal cultures, whereas cannabidiol + capsazepine prevented this effect. Therefore, we may assume that the release of TNF-alpha by glutamate-activated astrocytes may contribute to LID by exacerbating corticostriatal glutamatergic inputs excitability and maintaining astrocytes in an activated state through a self-reinforcing mechanism. (AU) | |
| FAPESP's process: | 14/25029-4 - Contribution of the neuroinflamation to L-DOPA induced dyskinesia |
| Grantee: | Elaine Aparecida Del Bel Belluz Guimarães |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 18/03482-0 - The action of cannabinoid drugs in glial-derived neuroinflammation process: a link to L-dopa-induced dyskinesia |
| Grantee: | Maurício dos Santos Pereira |
| Support Opportunities: | Scholarships abroad - Research Internship - Post-doctor |
| FAPESP's process: | 17/24304-0 - New perspectives in the use of drugs that modify atypical neurotransmitters in the treatment of neuropsychiatric disorders |
| Grantee: | Francisco Silveira Guimaraes |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 17/14207-7 - The action of cannabinoid drugs in L-dopa-induced dyskinesia: analysis of neuroinflammation and glutamate release in glial cells |
| Grantee: | Maurício dos Santos Pereira |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |