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• W2908248477 endingPage "1524" @default.
• W2908248477 startingPage "1505" @default.
• W2908248477 abstract "Intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin, are photosensitive neurons in the retina and are essential for non-image-forming functions, circadian photoentrainment, and pupillary light reflexes. Five subtypes of ipRGCs (M1–M5) have been identified in mice. Although ipRGCs are spared in several forms of inherited blindness, they are affected in Alzheimer's disease and aging, which are associated with impaired circadian rhythms. Huntington's disease (HD) is an autosomal neurodegenerative disease caused by the expansion of a CAG repeat in the huntingtin gene. In addition to motor function impairment, HD mice also show impaired circadian rhythms and loss of ipRGC. Here, we found that, in HD mouse models (R6/2 and N171-82Q male mice), the expression of melanopsin was reduced before the onset of motor deficits. The expression of retinal T-box brain 2, a transcription factor essential for ipRGCs, was associated with the survival of ipRGCs. The number of M1 ipRGCs in R6/2 male mice was reduced due to apoptosis, whereas non-M1 ipRGCs were relatively resilient to HD progression. Most importantly, the reduced innervations of M1 ipRGCs, which was assessed by X-gal staining in R6/2-OPN4 Lacz/+ male mice, contributed to the diminished light-induced c-fos and vasoactive intestinal peptide in the suprachiasmatic nuclei (SCN), which may explain the impaired circadian photoentrainment in HD mice. Collectively, our results show that M1 ipRGCs were susceptible to the toxicity caused by mutant Huntingtin. The resultant impairment of M1 ipRGCs contributed to the early degeneration of the ipRGC–SCN pathway and disrupted circadian regulation during HD progression. SIGNIFICANCE STATEMENT Circadian disruption is a common nonmotor symptom of Huntington's disease (HD). In addition to the molecular defects in the suprachiasmatic nuclei (SCN), the cause of circadian disruption in HD remains to be further explored. We hypothesized that ipRGCs, by integrating light input to the SCN, participate in the circadian regulation in HD mice. We report early reductions in melanopsin in two mouse models of HD, R6/2, and N171-82Q. Suppression of retinal T-box brain 2, a transcription factor essential for ipRGCs, by mutant Huntingtin might mediate the reduced number of ipRGCs. Importantly, M1 ipRGCs showed higher susceptibility than non-M1 ipRGCs in R6/2 mice. The resultant impairment of M1 ipRGCs contributed to the early degeneration of the ipRGC–SCN pathway and the circadian abnormality during HD progression." @default.
• W2908248477 created "2019-01-11" @default.
• W2908248477 creator A5023896092 @default.
• W2908248477 creator A5055034214 @default.
• W2908248477 creator A5059277705 @default.
• W2908248477 creator A5064132507 @default.
• W2908248477 creator A5076611137 @default.
• W2908248477 creator A5085149787 @default.
• W2908248477 date "2018-12-26" @default.
• W2908248477 modified "2023-09-30" @default.
• W2908248477 title "Degeneration of ipRGCs in Mouse Models of Huntington's Disease Disrupts Non-Image-Forming Behaviors Before Motor Impairment" @default.
• W2908248477 cites W1697684588 @default.
• W2908248477 cites W1773577399 @default.
• W2908248477 cites W1925629371 @default.
• W2908248477 cites W1929475465 @default.
• W2908248477 cites W1956487664 @default.
• W2908248477 cites W1960721561 @default.
• W2908248477 cites W1960895270 @default.
• W2908248477 cites W1964052956 @default.
• W2908248477 cites W1971238746 @default.
• W2908248477 cites W1971767494 @default.
• W2908248477 cites W1973765221 @default.
• W2908248477 cites W1973830626 @default.
• W2908248477 cites W1978580506 @default.
• W2908248477 cites W1984116068 @default.
• W2908248477 cites W1988983976 @default.
• W2908248477 cites W1992790774 @default.
• W2908248477 cites W1994612152 @default.
• W2908248477 cites W1996384089 @default.
• W2908248477 cites W2001653149 @default.
• W2908248477 cites W2006623685 @default.
• W2908248477 cites W2006872992 @default.
• W2908248477 cites W2008213690 @default.
• W2908248477 cites W2008522366 @default.
• W2908248477 cites W2009077913 @default.
• W2908248477 cites W2015419750 @default.
• W2908248477 cites W2019592351 @default.
• W2908248477 cites W2021985672 @default.
• W2908248477 cites W2022197238 @default.
• W2908248477 cites W2023951795 @default.
• W2908248477 cites W2026722283 @default.
• W2908248477 cites W2031280902 @default.
• W2908248477 cites W2031626699 @default.
• W2908248477 cites W2035136898 @default.
• W2908248477 cites W2035853180 @default.
• W2908248477 cites W2036239753 @default.
• W2908248477 cites W2038289966 @default.
• W2908248477 cites W2054938537 @default.
• W2908248477 cites W2055800694 @default.
• W2908248477 cites W2056888759 @default.
• W2908248477 cites W2057601872 @default.
• W2908248477 cites W2058375303 @default.
• W2908248477 cites W2058727942 @default.
• W2908248477 cites W2061683639 @default.
• W2908248477 cites W2066183013 @default.
• W2908248477 cites W2067508742 @default.
• W2908248477 cites W2067678115 @default.
• W2908248477 cites W2069186336 @default.
• W2908248477 cites W2070154168 @default.
• W2908248477 cites W2073148060 @default.
• W2908248477 cites W2073466689 @default.
• W2908248477 cites W2077061053 @default.
• W2908248477 cites W2079878023 @default.
• W2908248477 cites W2082456053 @default.
• W2908248477 cites W2090484885 @default.
• W2908248477 cites W2095099413 @default.
• W2908248477 cites W2095326601 @default.
• W2908248477 cites W2098204603 @default.
• W2908248477 cites W2107083462 @default.
• W2908248477 cites W2107522917 @default.
• W2908248477 cites W2115138453 @default.
• W2908248477 cites W2125106241 @default.
• W2908248477 cites W2125224248 @default.
• W2908248477 cites W2125248031 @default.
• W2908248477 cites W2126357344 @default.
• W2908248477 cites W2126572451 @default.
• W2908248477 cites W2128077939 @default.
• W2908248477 cites W2142125979 @default.
• W2908248477 cites W2143116460 @default.
• W2908248477 cites W2145749351 @default.
• W2908248477 cites W2147949992 @default.
• W2908248477 cites W2149920094 @default.
• W2908248477 cites W2155071292 @default.
• W2908248477 cites W2156902902 @default.
• W2908248477 cites W2162590238 @default.
• W2908248477 cites W2164172218 @default.
• W2908248477 cites W2166672740 @default.
• W2908248477 cites W2167645383 @default.
• W2908248477 cites W2171370174 @default.
• W2908248477 cites W2199562191 @default.
• W2908248477 cites W2389771398 @default.
• W2908248477 cites W2563059343 @default.
• W2908248477 cites W2606338729 @default.
• W2908248477 cites W2610585581 @default.
• W2908248477 cites W2773734774 @default.
• W2908248477 cites W4206144694 @default.
• W2908248477 cites W4237002893 @default.
• W2908248477 doi "https://doi.org/10.1523/jneurosci.0571-18.2018" @default.

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