High-salt diet does not boost neuroinflammation and neurodegeneration in a model of α-synucleinopathy

Aim Pre-clinical studies in models of multiple sclerosis and other inflammatory disorders suggest that high-salt diet may induce activation of the immune system and potentiate inflammation. However, high-salt diet constitutes a common non-pharmacological intervention to treat autonomic problems in synucleinopathies such as Parkinson's disease and multiple system atrophy. Since neuroinflammation plays an important pathogenic role in these neurodegenerative disorders, we asked here whether high-salt diet may aggravate the disease phenotype in a transgenic model of multiple system atrophy. Methods Nine-month-old PLP-h alpha Syn and matched wildtype mice received normal or high-salt diet for a period of 3 months. Behavioral, histological, and molecular analyses were performed to evaluate the effect of high-salt diet on motor decline, neuroinflammation, neurodegeneration, and alpha-synuclein accumulation in these mice. Results Brain subregion-specific molecular and histological analyses showed no deleterious effects of high-salt diet on the level of microglial activation. Moreover, neuroinflammation-related cytokines and chemokines, T cell recruitment or astrogliosis were unaffected by high-salt diet exposure. Behavioral testing showed no effect of diet on motor decline. High-salt diet was not related to the deterioration of neurodegeneration or alpha-synuclein accumulation in PLP-h alpha Syn mice. Conclusions Here, we demonstrate that high-salt diet does not aggravate neuroinflammation and neurodegeneration in PLP-h alpha Syn mice. Our findings discard a deleterious pro-neuroinflammatory effect of high-salt diet in multiple system atrophy.