Chronobiological function is affected in P23H line 1 transgenic rats

Abstract

Purpose: : To evaluate the circadian rhythms in P23H line 1 rats and to determine if they are affected by retinal degeneration.

Methods: : Male rats homozygous for the P23H rhodopsin mutation line 1 and male SD rats were evaluated during a 12 months period. All of them were individually housed and maintained during this time under controlled humidity (60%), temperature (23 ± 1°C) and under a 12-h light/dark cycle. Locomotor activity (LA) was monitored throughout the experiment by an intraperitoneal transmitter. Electroretinograms (ERG) were used to evaluate retinal function and retinas were evaluated by ICC looking for the degeneration pattern. Results were compared with those previously obtained for P23H line 3 in which retinal degeneration is slower.

Results: : The LA recordings from wild type and mutant animals showed no differences in the pattern of the mean waveform and the periodogram. However, a progressive decrease in the amplitude of the LA rhythm was observed in P23H rats, when compared to wild-type animals. The nonparametric analyses of the data showed a gradual decrease in the coupling strength of the LA rhythm to environmental zeitgebers (inter-daily stability, IS) and an increased rhythm fragmentation (intra-daily variability, IV) in P23H rats, as compared with wild type animals. The circadian changes are related to the rate of the degeneration. In 6 months P23H line 1 rats, the only remaining photoreceptor were cones, distributed in a disrupted single layer. B-wave amplitude was declined at this age. Changes were denoted in early ages than P23H line 3, in which both anatomical and functional retinal dysfunction is slower.

Conclusions: : Vision loss in P23H line 1 rats produces a progressive fragmentation of their circadian patterns.

Keywords: circadian rhythms • aging • retinal degenerations: hereditary