Keiichi Hiramoto1, Y Yamate2, E F Sato2. 1. Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan. hiramoto@suzuka-u.ac.jp. 2. Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.
Abstract
BACKGROUND: Long-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear. OBJECTIVES: In this study, ICR mice were used to study the effects of long-term UVA eye irradiation. METHODS: The eyes of mice were exposed to UVA from an FL20SBLB-A lamp three times a week for 1 year. Then, we analyzed memory and learning ability in the mice using water maze and step-through passive avoidance tests, and measured the levels of p53, Period2 (Per2), Clock, brain and muscle Arnt-like protein-1 (Bmal1), nicotinamide mononucleotide adenylyltransferase (NMNAT) activity, nicotinamide phosphoribosyltransferase (NAMPT) activity, nicotinamide adenine dinucleotide (NAD+), and sirtuin 1 (Sirt1) in the brains of treated and control animals. RESULTS: The results showed that the p53 level increased significantly following long-term UVA eye irradiation, whereas the levels of Period2, Bmal1, Clock, NMNAT and NAMPT activities, NAD+, and Sirt1 decreased significantly. Furthermore, we found that p53 inhibition ameliorated the UVA eye irradiation-induced depression of memory and learning ability. CONCLUSION: These results indicate that long-term UVA eye irradiation stimulates p53, inhibits the clock gene, and reduces Sirt1 production in the NAD+ constructional system, resulting in reduced memory and learning ability.
BACKGROUND: Long-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear. OBJECTIVES: In this study, ICR mice were used to study the effects of long-term UVA eye irradiation. METHODS: The eyes of mice were exposed to UVA from an FL20SBLB-A lamp three times a week for 1 year. Then, we analyzed memory and learning ability in the mice using water maze and step-through passive avoidance tests, and measured the levels of p53, Period2 (Per2), Clock, brain and muscle Arnt-like protein-1 (Bmal1), nicotinamide mononucleotide adenylyltransferase (NMNAT) activity, nicotinamide phosphoribosyltransferase (NAMPT) activity, nicotinamide adenine dinucleotide (NAD+), and sirtuin 1 (Sirt1) in the brains of treated and control animals. RESULTS: The results showed that the p53 level increased significantly following long-term UVA eye irradiation, whereas the levels of Period2, Bmal1, Clock, NMNAT and NAMPT activities, NAD+, and Sirt1 decreased significantly. Furthermore, we found that p53 inhibition ameliorated the UVA eye irradiation-induced depression of memory and learning ability. CONCLUSION: These results indicate that long-term UVA eye irradiation stimulates p53, inhibits the clock gene, and reduces Sirt1 production in the NAD+ constructional system, resulting in reduced memory and learning ability.
Entities:
Keywords:
Brain and muscle arnt-like protein 1; Clock; Nicotinamide adenine dinucleotide; P53; Sirtuin 1