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Genetic deletion of nitric oxide synthase 2 ameliorates Parkinson's disease pathology and neuroinflammation in a transgenic mouse model of synucleinopathy.

Genetic deletion of nitric oxide synthase 2 ameliorates Parkinson's disease pathology and neuroinflammation in a transgenic mouse model of synucleinopathy.

Authors :
Kim J
Han JY
Lee Y
Kim K
Choi YP
Chae S
Hoe HS
Source :
Molecular brain [Mol Brain] 2023 Jan 16; Vol. 16 (1), pp. 7. Date of Electronic Publication: 2023 Jan 16.
Publication Year :
2023

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 <superscript>A53T</superscript> ) and newly generated double transgenic mice with deletion of NOS2 (Syn <superscript>A53T</superscript> /NOS2 <superscript>-/-</superscript> ) were used. Compared with Syn <superscript>A53T</superscript> mice, the loss of nos2 decreased α-synuclein phosphorylation at serine 129 and reduced α-synuclein-induced microglial and astrocyte activation in Syn <superscript>A53T</superscript> /NOS <superscript>-/-</superscript> mice. Additionally, neuroinflammation-related gene clusters in the deep mesencephalic nucleus (DpMe) were altered in Syn <superscript>A53T</superscript> /NOS <superscript>-/-</superscript> mice compared with Syn <superscript>A53T</superscript> mice. Taken together, our results suggest that deletion of nos2 alleviates α-synuclein pathology and α-synuclein-associated neuroinflammatory responses in the brain.<br /> (© 2023. The Author(s).)

Details

Language :
English
ISSN :
1756-6606
Volume :
16
Issue :
1
Database :
MEDLINE
Journal :
Molecular brain
Publication Type :
Academic Journal
Accession number :
36647152
Full Text :
https://doi.org/10.1186/s13041-023-00996-1