Aging enhances the neuroinflammatory response and α-synuclein nitration in rats

The Lewy body is a pathological hallmark of Parkinson's disease. It has been revealed that the Lewy body contains nitrated α-synuclein which is prone to oligomerization. We tested the hypothesis that aging may enhance nitration of α-synuclein due to an exaggerated neuroinflammatory reaction such as an excessive induction of the inducible nitric oxide synthase, which occurs post-intrapallidal lipopolysaccharide (LPS) injection. Here, we show microglia activation and proinflammatory cytokine expression are more evident in the substantia nigra of elderly rats following intrapallidal LPS. In addition, greater nitration of proteins like α-synuclein occurs in the substantia nigra of 16-month-old rats versus 3-month-old rats, which is accompanied by a higher expression level of inducible nitric oxide synthase. These results imply that an exaggerated neuroinflammatory response that occurs with aging might be involved in the increase in prevalence of neurodegenerative diseases like Parkinson's disease.