Synergistic effects of lipopolysaccharide and rote-none on dopamine neuronal damage in rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE The etiology of Parkinson disease(PD)is still unknown.Until now,oxidative stress and neuroinflammation play a crucial role in the patho-genesis of PD.However,the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear.METHODS The changes in motor behavior,dopamine(DA)neurons quantification and their mitochondrial respiratory chain,glial cells activation and secreted cytokines,Nrf2 signal-ing pathway,and redox balance in the brain of rats were evaluated.RESULTS Lipopolysaccharide(LPS)-induced neuroinflammation and rotenone(ROT)-induced oxidative stress synergistically aggravated motor dysfunc-tion,DA neuron damage,activation of glial cells,and release of related mediators,activation of Nrf2 signaling and destruction of oxidative balance.In addition,further studies indicated that after ROT-induced oxidative stress caused direct damage to DA neurons,LPS-induced inflammatory effects had stronger promoting neurotoxic effects on the above aspects.CONCLUSION Neuroinflammation and oxidative stress synergistically aggravated DA neuronal loss.Furtherly,oxidative stress followed by neuroinflammation caused more DA neuro-nal loss than neuroinflammation followed by oxidative stress.