29. Effects of cannabinoids on microglial activation and tyrosine hydroxylase expression in substancia nigra of rats with 6-hydroxydopamine-induced hemiparkinsonism

Abstract

Recent studies have pointed out the cannabinoid system as neuroprotective in different models of neurodegenerative diseases, such as Parkinson’s Disease (PD), particularly by triggering anti-inflammatory events. However, the data in the literature are still controversial, especially regarding to receptor-dependent and/or antioxidant effects. We investigated the effects of the treatment with two cannabinoid compounds, ACEA (CB1 receptor agonist, 4 mg/kg-daily injections during 4 days post-lesion), and AM404 (anandamida uptake inhibitor, 2 mg/kg-daily injections during 5 days post-lesion), on the expression of tyrosine hydroxylase (TH), GFAP (astrocyte marker), and OX-42 (microglia marker), evaluated by immunohistochemistry and/or immunoblotting in the substancia nigra (SN) of rat brains unilaterally injected with 6-hydroxy-dopamine. The ACEA group exhibited a decrease about 30% in the TH levels and an increase about 24% in the OX-42 expression in relation to the control group (treated with vehicle DMSO). The AM404 group presented a decrease about 10% in the expression of TH and an increase about 20% and 26% in the expression of GFAP and OX-42, respectively, compared with the DMSO group. Our results show, therefore, that the treatment with both cannabinoid compounds seems to promote an increase in the microglial activation in the SN and an increment of TH-neurons lost induced by the 6-hydroxy-dopamine. This study adds information about the role of cannabinoid system and cannabinoid compounds as possible therapeutic tools in PD. FAPESP and CNPq.