p53 and clock genes play an important role in memory and learning ability depression due to long-term ultraviolet A eye irradiation

p53 and clock genes play an important role in memory and learning ability depression due to long-term ultraviolet A eye irradiation
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DOI:
10.1007/s43630-021-00055-5
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发表时间:
2021-05
影响因子:
3.1
通讯作者:
K. Hiramoto;Y. Yamate;E. Sato
K. Hiramoto;Y. Yamate;E. Sato
中科院分区:
化学3区
文献类型:
--
作者:
K. Hiramoto;Y. Yamate;E. Sato

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背景长期紫外线A(UVA)眼部照射会降低小鼠的记忆和学习能力。本研究以ICR小鼠为研究对象,研究了长期UVA眼部照射对小鼠眼部的影响。方法用FL20SBLB-A灯照射小鼠眼部,每周3次,持续1年。用水迷宫和避暗被动回避实验分析小鼠的学习记忆能力,并测定治疗组和对照组小鼠脑内P53、PER2、Clock、脑和肌肉Arnt样蛋白-1(BMal1)、烟酰胺单核苷酸腺苷转移酶(NMNAT)活性、烟酰胺磷酸核糖基转移酶(NAMPT)活性、烟酰胺腺嘌呤二核苷酸(NAD+)和sirtuin 1(Sirt1)水平。结论长期的UVA眼照射可刺激P53基因,抑制时钟基因,减少NAD+结构系统中Sirt1的产生,导致记忆和学习能力下降。
BackgroundLong-term ultraviolet A (UVA) eye irradiation decreases memory and learning ability in mice. However, the underlying mechanism is still unclear.ObjectivesIn this study, ICR mice were used to study the effects of long-term UVA eye irradiation.MethodsThe 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.ResultsThe 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.ConclusionThese 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.Graphic abstract