Blue light exposure-dependent improvement in robustness of circadian rest-activity rhythm in aged rats

Abstract

The aging effects on circadian rhythms have diverse implications including changes in the pattern of rhythmic expressions, such as a wide fragmentation of the rhythm of rest-activity and decrease in amplitude of activity regulated by the suprachiasmatic nucleus (SCN). The study of blue light on biological aspects has received great current interest due, among some aspects, to its positive effects on psychiatric disorders in humans. This study aims to evaluate the effect of blue light therapy on the SCN functional aspects, through the evaluation of the rest-activity rhythm, in aging rats. For this, 33 sixteen-months-old male Wistar rats underwent continuous records of locomotor activity and were exposed to periods of 6 hours of blue light during the first half of the light phase (Zeitgeber times 0-6) for 14 days. After this, the rats were maintained at 12h:12h light:dark cycle to check the long-term effect of blue light for 14 days. Blue light repeated exposure showed positive effects on the rhythmic variables of locomotor activity in aged rats, particularly the increase in amplitude, elevation of rhythmic robustness, phase advance in acrophase, and greater consolidation of the resting phase. This effect depends on the presence of daily blue light exposure. In conclusion, our results indicate that blue light is a reliable therapy to reduce circadian dysfunctions in aged rats, but other studies assessing how blue light modulates the neural components to modulate this response are still needed.

Fig 1. Diagrammatic representation of the blue light therapy (6+6h:12h blue+white light:dark) and housing conditions (12h:12h light:dark).

Yellow indicates the light phase (L); gray indicates the dark phase (D).

Fig 2. Locomotor activity pattern of young rats submitted to the Basal LD (12h:12h light:dark) and Blue light LD (6+6h:12h blue+white light:dark) conditions at different times of the cycle.

Descriptive graph of the % area under curve (%AUC) of young rats (n = 12) locomotor activity submitted to the Basal LD (for 14 days) and Blue light LD (for 14 days) conditions. Values expressed as median ± interquartile range. Drawings of each column represents the range selected to represent part of a cycle. Wilcoxon test, p-value: p<0.05; * indicates significant difference compared to Basal LD; ZT, zeitgeber time; LD, light:dark.

Fig 3. Actogram and mean activity curves showing the locomotor activity rhythm of an aged rat submitted to the Basal LD (12h:12h light:dark), Blue light LD (6+6h:12h blue+white light:dark), and Post-blue light LD (12h:12h light:dark) conditions.

(A) Actogram of the activity plotted in 48 h represented on the line and days arranged sequentially from top to bottom. Vertical deflections represent the activity value for each record collected at 5-minute intervals. The white/black bar at the top indicates the 12h:12h light:dark cycle and the blue shading indicates the time of exposure to blue light in relation to hours. Days 1–14: Baseline recording. Days 15–28: Blue light therapy. Days 29–42: Post-blue light therapy. (B) Mean activity curves of aged rat versus hours at Basal LD, Blue light LD, and Post-blue light LD stages. The white/black bar at the top indicates the 12h:12h light:dark cycle. Blue shading indicates the time of exposure to blue light in relation to hours and the gray shading represents the animal’s activity phase. The sine wave represents the rhythm-adjusted mean (Mesor) and the vertical line represents the peak of activity (Acrophase) of the animal. a.u., arbitrary unit; L-D, light:dark cycle.

Fig 4. Locomotor activity pattern of aged rats submitted to the Basal LD (12h:12h light:dark), Blue light LD (6+6h:12h blue+white light:dark), and Post-blue light LD (12h:12h light:dark) conditions at different times of the cycle.

Descriptive graph of the % area under curve (%AUC) of aged rats (n = 33) locomotor activity submitted to the Basal LD (for 14 days), Blue light LD (for 14 days), and Post-blue light LD (for 14 days) conditions. Values expressed as median ± interquartile range. Drawings of each column represents the range selected to represent part of a cycle. Wilcoxon test, p-value: p<0.05; * indicates significant difference compared to Basal LD; # indicates significant difference compared to Blue Light LD; ZT, zeitgeber time; LD, light:dark.

Fig 5. Variables derived from cosinor curve fitting.

Descriptive graphs of the amplitude (A), acrophase (B), and total daily activity (C) of aged rats (n = 33) locomotor activity submitted to the Basal LD (for 14 days), Blue light LD (for 14 days), and Post-blue light LD (for 14 days) conditions. Values expressed as median ± interquartile range. Circles, squares, and triangles represent values of each animal evaluated. a.u., arbitrary unit; ZT, zeitgeber time; LD, light:dark; Wilcoxon test, p-value: *p<0.05; ***p<0.001.

Fig 6. Non-parametric variables.

Descriptive graphs of the IS (A), M10 (B), L5 (C), and IV (D) of aged rats (n = 33) locomotor activity submitted to the Basal LD (for 14 days), Blue light LD (for 14 days), and Post-blue light LD (for 14 days) conditions. Values expressed as median ± interquartile range. Circles, squares, and triangles represent values of each animal evaluated. a.u., arbitrary unit; IS, interdaily stability; M10, most active ten-hour period; L5, least active five-hour period; IV, intradaily variability; LD, light:dark; Wilcoxon test, p-value: *p<0.05; **p<0.01; ***p<0.001; ns, not significant.