Abstract
Accumulating evidence indicates that microglia activation is associated with an increased risk for developing Parkinson’s disease (PD). With the progressive and selective degeneration of dopaminergic (DA) neurons, proinflammatory cytokines are elevated in the substantia nigra (SN) of PD patients. Thus, anti-inflammation has become one of the therapeutic strategies of PD. Eriocalyxin B (EriB), a diterpenoid isolated from Isodoneriocalyx, was previously reported to have anti-inflammatory effects. MPTP mouse model and MPP+ cell model were prepared to detect the role of EriB in regulating microglia activation and neuron protection. Midbrain tissue and primary cultured microglia and neuron were used to examine microglia activation and neuron damage by immunofluorescence, real-time PCR, western-blot and Elisa assay. Open field activity test was to evaluate the changes of behavioral activity in MPTP-induced PD mouse model. EriB was efficacious in protecting DA neurons by inhibiting microglia activation in PD mice model. Treatment with EriB led to amelioration of disordered sports of PD mice model, which correlated with reduced microglia-associated inflammation and damaged DA neurons. EriB treatment abolished MPP+ induced microglia activation damages to DA neurons in a microglia and DA neurons co-culture system. The underlying mechanism of EriB-induced protective effects involved inhibition of microglia associated proinflammatory cytokines production through the phenotypic shift of microglial cells as well as activator of transcription and nuclear factor-κB (NF-κB) signaling pathways. These findings demonstrate that EriB exerts potent anti-inflammatory effects through selective modulation of microglia activation by targeting NF-κB signaling pathways, thus exerting the protective effect against on MPP+-induced DA neurons injury. This study may provide insights into the promising therapeutic role of EriB for PD.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disorder which is characterized by the loss of dopamine (DA) neurons in the ventral midbrain with cell bodies in the substantia nigra pars compacta (SNpc) [1]
Eriocalyxin B (EriB) attenuated DA neurons damage and alleviated motor deficits in PD mice model To determine whether EriB play a role in neuron protection in MPTP mouse model, we examined the status of tyrosine hydroxilase (TH) positive neurons damage in SN area of mouse brain
EriB and MPTP administration starting simultaneously in adult mice to determine the protective role of EriB by measuring the numbers of injured DA neurons and the mean behavioral activity score compared with normal control
Summary
Parkinson’s disease (PD) is a common neurodegenerative disorder which is characterized by the loss of dopamine (DA) neurons in the ventral midbrain with cell bodies in the substantia nigra pars compacta (SNpc) [1]. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6 and Evidence suggests that over activation of microglia in SNpc is a key factor in DA neuronal death and the occurrence of PD [5, 6]. Strong evidence implicates TNF plays a key role in the pathophysiology of PD, in early stage and in the late stage, and it could lead to the release of inflammatory cytokines. We discuss the key experimental evidence implicating microglia associated inflammation response in the progressive degeneration of the DA neurons and their potential contribution to the pathological process of PD, and we describe studies performed in the PD mice model that indicate potential therapeutic effects of EriB on PD and delineate underlying molecular mechanisms
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