Circadian rhythm of Period1 clock gene expression in NOS amacrine cells of the mouse retina.
The vertebrate retina contains self-sustained circadian clocks that broadly influence retinal physiology. In the present study, we have examined the relationship of nitric oxide, GABAergic and glycinergic inner retinal neurons with expression of a reporter for the circadian clock gene Period1 (Per1). Using Per1 : :GFP transgenic mice, we found that 72% of brain nitric oxide synthase (bNOS) expressing amacrine cells (NOS amacrine cells) sampled during the daytime were also immunoreactive for Per1-driven GFP. The number of bright GFP(+) NOS(+) cells was greater at Zeitgeber time (ZT) 10 than at 22, and this pattern persisted in retinas from animals which were placed in constant darkness [Circadian time (CT) 10 vs. 22]. Intensities of GFP-IR for individual NOS amacrine cells were analyzed at ZT4, 10, 16 and 22, with the peak value occurring at ZT10. Similar results were obtained from retinas sampled at CT4, 10, 16 and 22 in constant darkness, indicating that an endogenous circadian clock drives the transcription of the Per1 clock gene within NOS amacrine cells. The predominance of Per1 : :GFP(+) amacrine cells (82%), was immunoreactive to glutamate decarboxylase 65, but no Per1 : :GFP(+) amacrine cells colabeled with a glycine transporter 1 antibody. The results demonstrate circadian rhythms in Per1 promoter activation in nitric oxide (NO) and GABA secreting amacrine cells, and suggest that NO and GABA could be controlled by circadian clock mechanisms in the mammalian retina.
Department of Biological Sciences, Vanderbilt University, VU Station B, Box 35-1634, Nashville, TN 37235-1634, USA.
Dao-Qi
DQ
Zhang
Tongrong
T
Zhou
Guo-Xiang
GX
Ruan
Douglas G
DG
McMahon
D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology*; D015870:Gene Expression / Q000502:physiology; D005998:Glycine / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018797:Cell Cycle Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D049452:Green Fluorescent Proteins; D009569:Nitric Oxide; D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D005998:Glycine