Roles Of Glial Cells In Paraquat-induced Neurotoxicity And HDAC Inhibitors-mediated Neuroprotection On Dopaminergic Neurons

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by a progressive and selective degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta. To date, the etiology of PD largely remains unknown and there is no curative therapy. However, increasing evidence has suggested that environmental factor like viral infection, brain trauma and pesticide exposure are associated with the development of PD. Glial cells especially microglia-mediated neuroinflammation might be a common mechanism underlying the neurotoxicity induced by different factors. Thus, anti-inflammation has become one of the therapeutic strategies of PD. In addition, providing neurotrophic support is another way to pursue neuroprotection. Numerous studies have shown that neurotrophic factors are neuroprotective in various PD models. Using rat midbrain neuron-glia co-cultures and neuron- or glia-enriched cultures, the current study observed the role of microglia in neuroinflammation causing DA neurotoxicity and that in the neuroprotective mechanism of anti-inflammation, also investigated the neurotrophic mechanism in the DA neuroprotection through increasing histone acetylation at BDNF and GDNF gene promoter regions in astrocytes.Role of microglia in paraquat-induced DA neurodegenerationExposure to some environmental toxins, e.g. pesticide rotenone and herbicide paraquat (PQ), has been implicated in the development of PD.