Abstract
Neuroinflammation plays a very important role in the pathogenesis of Parkinson’s disease (PD). After activation, microglia produce pro-inflammatory mediators that damage surrounding neurons. Consequently, the inhibition of microglial activation might represent a new therapeutic approach of PD. Vanillin has been shown to protect dopaminergic neurons, but the mechanism is still unclear. Herein, we further study the underlying mechanisms in lipopolysaccharide (LPS)-induced PD models. In vivo, we firstly established rat models of PD by unilateral injection of LPS into substantia nigra (SN), and then examined the role of vanillin in motor dysfunction, microglial activation and degeneration of dopaminergic neurons. In vitro, murine microglial BV-2 cells were treated with vanillin prior to the incubation of LPS, and then the inflammatory responses and the related signaling pathways were analyzed. The in vivo results showed that vanillin markedly improved the motor dysfunction, suppressed degeneration of dopaminergic neurons and inhibited microglial over-activation induced by LPS intranigral injection. The in vitro studies demonstrated that vanillin reduces LPS-induced expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2), IL-1β, and IL-6 through regulating ERK1/2, p38 and NF-κB signaling. Collectively, these data indicated that vanillin has a role in protecting dopaminergic neurons via inhibiting inflammatory activation.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disorder that affects millions of people in the world [1,2,3]
Further research showed that vanillin inhibited LPS-induced activation of microglia. These results indicated that the neuroprotection effect of vanillin on LPS-induced PD rat model is closely associated with inhibiting activation of microglia
The results obtained in this study showed that vanillin treatment markedly inhibits LPS-induced p38, ERK1/2 and NF-κB p65 phosphorylation, but has no effect on phosphorylation of JNK1/2, demonstrating that vanillin suppress the inflammatory response via inhibiting ERK1/2, p38 and NF-κB p65 phosphorylation
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disorder that affects millions of people in the world [1,2,3]. VVaanniilllliinn IInnhhiibbiittss LLPPSS--IInndduucceedd AAccttiivvaattiioonn ooff MMiiccrroogglliiaa iinn tthhee SSNN. LPS-induced PD rat model is widely used to study the effect of neuroinflammation on the dopaminergic system. The result of TH immunohistological analysis demonstrated that vanillin administration markedly inhibited LPS-induced death of dopaminergic neuron. We found that LPS significantly increased the expression of pro-inflammatory mediators, and vanillin markedly reduced that. These results further confirmed that the neuroprotection effect of vanillin is involved in its anti-inflammatory function. The results obtained in this study showed that vanillin treatment markedly inhibits LPS-induced p38, ERK1/2 and NF-κB p65 phosphorylation, but has no effect on phosphorylation of JNK1/2, demonstrating that vanillin suppress the inflammatory response via inhibiting ERK1/2, p38 and NF-κB p65 phosphorylation
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have