Parikh Shivang, Parikh Roma, Harari Marco, Weller Aron, Bikovski Lior, Levy Carmit
Department of Human Genetics and Biochemistry, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Dead Sea and Arava Science Center, Masada DMZ Medical Center, Ein Bokek, Israel.
Front Behav Neurosci. 2023 Dec 12;17:1281274. doi: 10.3389/fnbeh.2023.1281274. eCollection 2023.
The first cells affected by UVB exposure are epidermal keratinocytes, and p53, the genome guardian, is activated in these cells when skin is exposed to UVB. UVB exposure induces appetite, but it remains unclear whether p53 in epidermal keratinocytes plays a role in this appetite stimulation.
Here we found that food intake was increased following chronic daily UVB exposure in a manner that depends on p53 expression in epidermal keratinocytes. conditional knockout in epidermal keratinocytes reduced food intake in mice upon UVB exposure.
To investigate the effects of p53 activation following UVB exposure, mice behavior was assessed using the staircase, open-field, elevated-plus maze, and conditioned-place preference tests. In addition to effects on appetite, loss of p53 resulted in anxiety-related behaviors with no effect on activity level.
Since skin p53 induces production of β-endorphin, our data suggest that UVB-mediated activation of p53 results in an increase in β-endorphin levels which in turn influences appetite. Our study positions UVB as a central environmental factor in systemic behavior and has implications for the treatment of eating and anxiety-related disorders.
受紫外线B(UVB)照射影响的首批细胞是表皮角质形成细胞,当皮肤暴露于UVB时,基因组守护者p53在这些细胞中被激活。UVB照射会诱导食欲,但目前尚不清楚表皮角质形成细胞中的p53是否在这种食欲刺激中发挥作用。
我们发现,每日长期暴露于UVB后,食物摄入量会增加,且这种增加取决于表皮角质形成细胞中p53的表达。表皮角质形成细胞中的条件性基因敲除会降低UVB照射后小鼠的食物摄入量。
为研究UVB照射后p53激活的影响,使用阶梯试验、旷场试验、高架十字迷宫试验和条件性位置偏爱试验评估小鼠行为。除了对食欲的影响外,p53缺失还导致了与焦虑相关的行为,而对活动水平没有影响。
由于皮肤中的p53会诱导β-内啡肽的产生,我们的数据表明,UVB介导的p53激活会导致β-内啡肽水平升高,进而影响食欲。我们的研究将UVB定位为全身行为的核心环境因素,并对饮食和焦虑相关疾病的治疗具有启示意义。