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- Title
Degeneration of ipRGCs in Mouse Models of Huntington's Disease Disrupts Non-Image-Forming Behaviors Before Motor Impairment.
- Authors
Meng-Syuan Lin; Po-Yu Liao; Hui-Mei Chen; Ching-Pang Chang; Shih-Kuo Chen; Yijuang Chern
- 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 th e 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-Ml ipRGCs were relatively resilient to HD progression. Most importantly, the reduced innervations of Ml ipRGCs, which was assessed by X-gal staining in R6/2-OPN4Lacz/+ 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 Ml ipRGCs were susceptible to the toxicity caused by mutant Huntingtin. The resultant impairment of Ml ipRGCs contributed to the early degeneration of the ipRGC-SCN pathway and disrupted circadian regulation during HD progression.
- Subjects
HUNTINGTON disease
- Publication
Journal of Neuroscience, 2019, Vol 39, Issue 8, p1505
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0571-18.2018