Transient receptor potential vanilloid 1 exhibits neuroprotective effects in LPS-induced dopaminergic neuronal death in the suabstantia nigra in vivo.
Parkinson？s disease (PD) is a motor disorder which is progressive degeneration of the nigrostriatal dopaminergic pathway. There is no cure for PD and besides the etiology of this disease was limited understood. Neuroinflammation have been proposed to play a role in the pathogenesis of PD. Recent evidence implicates the transient receptor potential vanilloid subtype 1 (TRPV1) leads to neuroprotective effects by anti-inflammtory action. The main purpose of this thesis is to investigate the functional effects of capsaicin (CAP), the TRPV1 agonist, in LPS-induced in vivo PD model. To do that, we investigated the LPS-induced inflammatory response including dopaminergic (DA) neuronal degeneration, microglia activation, inflammatory mediator expression and infiltration of peripheral immune cells in the SN. Additionally, we surveyed whether CAP would have ability to DA neuronal protection against LPS and how CAP regulates the inflamed condition. We also confirmed whether these effects of CAP were mediated by TRPV1. Immunostaining, RT-PCR and western blot analysis showed that CAP attenuates LPS-induced production of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and ROS while CAP increases Arginase 1 and CD206, M2 macrophage markers. In addition, CAP protected nigral DA neurons from LPS-induced neurotoxicity. This neuroprotective effect was reversed by capsazepine, a TRPV1 antagonist, indicative of TRPV1 involvement. However CAP could not block the infiltration of peripheral immune cells. Based on these results, we found that CAP exhibits the neuroprotective effects through regulating the immune cell phenotypes. The present results suggest that CAP may be beneficial for the treatment of neurodegenerative diseases, such as PD that is associated with neuroinflammation via TRPV1.
TPRV1, Parkinson's disease, microglia, inflammation, infiltration, M1 M2
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