Synergistic effects of lipopolysaccharide and rotenone on dopamine neuronal damage in rats

IntroductionThe etiology of Parkinson's disease (PD) is still unknown. Until now, oxidative stress and neuroinflammation play a crucial role in the pathogenesis of PD. However, the specific synergistic role of oxidative stress and neuroinflammation in the occurrence and development of PD remains unclear. MethodsThe changes in motor behavior, dopamine (DA) neurons quantification and their mitochondrial respiratory chain, glial cells activation and secreted cytokines, Nrf2 signaling pathway, and redox balance in the brain of rats were evaluated. ResultsLipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, 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. ConclusionsNeuroinflammation and oxidative stress synergistically aggravated DA neuronal loss. Furtherly, oxidative stress followed by neuroinflammation caused more DA neuronal loss than neuroinflammation followed by oxidative stress.

Automated summary

The etiology of Parkinson's disease (PD) is still unknown, but oxidative stress and neuroinflammation play a crucial role in its pathogenesis. This study found that lipopolysaccharide (LPS)-induced neuroinflammation and rotenone (ROT)-induced oxidative stress synergistically aggravated motor dysfunction, dopamine neuron damage, glial cell activation, release of related mediators, activation of Nrf2 signaling, and disruption of oxidative balance in the rat brain. Furthermore, oxidative stress followed by neuroinflammation caused more dopamine neuronal loss than neuroinflammation followed by oxidative stress.