Genetic deletion of nitric oxide synthase 2 ameliorates Parkinson’s disease pathology and neuroinflammation in a transgenic mouse model of synucleinopathy
Ji‐Eun Kim, Jung‐Youn Han, Yujeong Lee, Kipom Kim, Young Pyo Choi, Sehyun Chae, Hyang‐Sook Hoe
Abstract
Abstract Studies of mouse models of Alzheimer's disease (AD) have demonstrated that nitric oxide synthase 2 (NOS2) is involved in AD pathology. However, the effects of NOS2 on the pathology of Parkinson’s disease (PD) are not well studied. To address this gap, we examined the impact of NOS2 on disease-associated phenotypes in a mouse model of PD. Transgenic mice carrying the A53T mutation of α-synuclein (Syn A53T ) and newly generated double transgenic mice with deletion of NOS2 (Syn A53T /NOS2 −/− ) were used. Compared with Syn A53T mice, the loss of nos2 decreased α-synuclein phosphorylation at serine 129 and reduced α-synuclein-induced microglial and astrocyte activation in Syn A53T /NOS −/− mice. Additionally, neuroinflammation-related gene clusters in the deep mesencephalic nucleus (DpMe) were altered in Syn A53T /NOS −/− mice compared with Syn A53T mice. Taken together, our results suggest that deletion of nos2 alleviates α-synuclein pathology and α-synuclein-associated neuroinflammatory responses in the brain.