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Bidirectional Neural Interaction Between Central Dopaminergic and Gut Lesions in Parkinson's Disease Models

Bidirectional Neural Interaction Between Central Dopaminergic and Gut Lesions in Parkinson's Disease Models

Pablo Garrido-Gil, Ana I Rodriguez-Perez, Antonio Dominguez-Meijide, Maria J Guerra, Jose L Labandeira-Garcia

Mol Neurobiol. 2018 Sep;55(9):7297-7316.

PMID: 29404956

Abstract:

The exact mechanism of gut dysfunction in Parkinson's disease and, conversely, the role of gut pathology in brain dopaminergic degeneration are controversial. We investigated the effects of nigral lesions on the colonic neurotransmission, the effect of gut inflammation on the nigrostriatal dopaminergic function, and the possible involvement of the vagus nerve and the local renin-angiotensin system (RAS). Nigrostriatal dopamine depletion was performed by bilateral injection 6-hydroxydopamine, and gut inflammation was induced by dextran sulfate sodium salt treatment in rats and mice, respectively, with or without vagal disruption. A decrease in central dopamine levels induced a decrease in colonic dopamine types 1 and 2 receptor expression together with an increase in the colonic levels of dopamine and a decrease in the levels of acetylcholine, which may explain a decrease in gut motility. Central dopaminergic depletion also induced an increase in the colonic levels of inflammatory and oxidative stress markers together with activation of the pro-inflammatory arm of the local RAS. Mice with acute (1 week) or subchronic (3 weeks) gut inflammation did not show a significant increase in colonic α-synuclein and phosphorylated α-synuclein expression during this relatively short survival period. Interestingly, we observed early changes in the nigrostriatal dopaminergic homeostasis, dopaminergic neuron death, and increased levels of nigral pro-inflammatory markers and RAS pro-inflammatory activity. The present results show that a dysregulation of the neural bidirectional gut-brain interaction may explain the early gut disturbances observed in parkinsonian patients, and also the increase in vulnerability of nigral dopaminergic neurons after gut inflammation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS74844	Dextran sulfate sodium salt			Price

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