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• W4319984865 abstract "Clinical and pathological evidence revealed that α-synuclein (α-syn) pathology seen in PD patients starts in the gut and spreads via anatomically connected structures from the gut to the brain. Our previous study demonstrated that depletion of central norepinephrine (NE) disrupted brain immune homeostasis, producing a spatiotemporal order of neurodegeneration in the mouse brain. The purpose of this study was 1) to determine the role of peripheral noradrenergic system in the maintenance of gut immune homeostasis and in the pathogenesis of PD and 2) to investigate whether NE-depletion induced PD-like α-syn pathological changes starts from the gut. For these purposes, we investigated time-dependent changes of α-synucleinopathy and neuronal loss in the gut following a single injection of DSP-4 (a selective noradrenergic neurotoxin) to A53T-SNCA (human mutant α-syn) over-expression mice. We found DPS-4 significantly reduced the tissue level of NE and increased immune activities in gut, characterized by increased number of phagocytes and proinflammatory gene expression. Furthermore, a rapid-onset of α-syn pathology was observed in enteric neurons after 2 weeks and delayed dopaminergic neurodegeneration in the substantia nigra was detected after 3-5 months, associated with the appearance of constipation and impaired motor function, respectively. The increased α-syn pathology was only observed in large, but not in the small, intestine, which is similar to what was observed in PD patients. Mechanistic studies reveal that DSP-4-elicited upregulation of NADPH oxidase (NOX2) initially occurred only in immune cells during the acute intestinal inflammation stage, and then spread to enteric neurons and mucosal epithelial cells during the chronic inflammation stage. The upregulation of neuronal NOX2 correlated well with the extent of α-syn aggregation and subsequent enteric neuronal loss, suggesting that NOX2-generated reactive oxygen species play a key role in α-synucleinopathy. Moreover, inhibiting NOX2 by diphenyleneiodonium or restoring NE function by salmeterol (a β2-receptor agonist) significantly attenuated colon inflammation, α-syn aggregation/propagation, and enteric neurodegeneration in the colon and ameliorated subsequent behavioral deficits. Taken together, our model of PD shows a progressive pattern of pathological changes from the gut to the brain and suggests a potential role of the noradrenergic dysfunction in the pathogenesis of PD." @default.
• W4319984865 created "2023-02-11" @default.
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• W4319984865 date "2023-02-10" @default.
• W4319984865 modified "2023-10-03" @default.
• W4319984865 title "Dysfunction of the noradrenergic system drives inflammation, α-synucleinopathy, and neuronal loss in mouse colon" @default.
• W4319984865 cites W118400788 @default.
• W4319984865 cites W1480945180 @default.
• W4319984865 cites W1646903440 @default.
• W4319984865 cites W1957893233 @default.
• W4319984865 cites W1962674088 @default.
• W4319984865 cites W1964642241 @default.
• W4319984865 cites W1971599063 @default.
• W4319984865 cites W1979237351 @default.
• W4319984865 cites W1994774394 @default.
• W4319984865 cites W1995281235 @default.
• W4319984865 cites W2007576700 @default.
• W4319984865 cites W2007870142 @default.
• W4319984865 cites W2009786758 @default.
• W4319984865 cites W2026455995 @default.
• W4319984865 cites W2035475717 @default.
• W4319984865 cites W2062048315 @default.
• W4319984865 cites W2073279468 @default.
• W4319984865 cites W2073449985 @default.
• W4319984865 cites W2078621823 @default.
• W4319984865 cites W2083048982 @default.
• W4319984865 cites W2085128107 @default.
• W4319984865 cites W2087554951 @default.
• W4319984865 cites W2103641388 @default.
• W4319984865 cites W2104632419 @default.
• W4319984865 cites W2107966431 @default.
• W4319984865 cites W2110235509 @default.
• W4319984865 cites W2121624248 @default.
• W4319984865 cites W2124680201 @default.
• W4319984865 cites W2124680543 @default.
• W4319984865 cites W2128414222 @default.
• W4319984865 cites W2142483035 @default.
• W4319984865 cites W2147489823 @default.
• W4319984865 cites W2148908418 @default.
• W4319984865 cites W2155208388 @default.
• W4319984865 cites W2161057248 @default.
• W4319984865 cites W2168451388 @default.
• W4319984865 cites W2195120335 @default.
• W4319984865 cites W2237612852 @default.
• W4319984865 cites W2294532941 @default.
• W4319984865 cites W2325477312 @default.
• W4319984865 cites W2328023807 @default.
• W4319984865 cites W2417670847 @default.
• W4319984865 cites W2462036771 @default.
• W4319984865 cites W2485663801 @default.
• W4319984865 cites W2518460556 @default.
• W4319984865 cites W2558041282 @default.
• W4319984865 cites W2575605891 @default.
• W4319984865 cites W2605297820 @default.
• W4319984865 cites W2626849072 @default.
• W4319984865 cites W2738201977 @default.
• W4319984865 cites W2751317059 @default.
• W4319984865 cites W2753292637 @default.
• W4319984865 cites W2792878374 @default.
• W4319984865 cites W2801299411 @default.
• W4319984865 cites W2811494262 @default.
• W4319984865 cites W2883197717 @default.
• W4319984865 cites W2889286462 @default.
• W4319984865 cites W2889788554 @default.
• W4319984865 cites W2921186604 @default.
• W4319984865 cites W2943725638 @default.
• W4319984865 cites W2951348834 @default.
• W4319984865 cites W2953534538 @default.
• W4319984865 cites W2954689737 @default.
• W4319984865 cites W2988130908 @default.
• W4319984865 cites W3006261429 @default.
• W4319984865 cites W3006477212 @default.
• W4319984865 cites W3018307087 @default.
• W4319984865 cites W3082630282 @default.
• W4319984865 cites W3084886839 @default.
• W4319984865 cites W3091476980 @default.
• W4319984865 cites W3121396168 @default.
• W4319984865 cites W3127379712 @default.
• W4319984865 cites W3167954774 @default.
• W4319984865 cites W3196241139 @default.
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• W4319984865 doi "https://doi.org/10.3389/fimmu.2023.1083513" @default.
• W4319984865 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36845109" @default.
• W4319984865 hasPublicationYear "2023" @default.
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