Wu Xi, Li Ping, Tao Junyan, Chen Xiong, Zhang Aihua
The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang 550025, China.
State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, China.
Toxics. 2023 Feb 18;11(2):191. doi: 10.3390/toxics11020191.
Methylmercury (MeHg) is a global pollutant with established toxic effects on the central nervous system (CNS). However, early events and early-warning biomarkers of CNS damage following exposure to low-dose MeHg are still lacking. This study aimed to investigate whether subchronic low-dose MeHg exposure had adverse effects on the cerebral telomere length, as well as serum melatonin and its urinary metabolite 6-sulfatoxymelatonin (aMT6s) in rats. Sixteen male Sprague Dawley rats were divided into two groups. Group I was the control group. In group II, rats were exposed to MeHg by gavage at a dose of 0.1 mg/kg/day for 3 months. This study revealed that MeHg exposure resulted in impairment of learning and memory ability, a slightly reduced number of neurons and an irregular arrangement of neurons in the hippocampus. It also significantly accelerated telomere shortening in the cerebral cortex, hippocampus and hypothalamus. Moreover, MeHg exposure decreased the levels of melatonin in serum and aMT6s in urine, partly by suppressing the synthesis of 5-hydroxytryptamine (5-HT) in the brain but promoted the expression of melatonin-catalyzing AANAT and ASMT. Importantly, cerebral telomere length was positively correlated with MT and aMT6s after MeHg exposure. These results suggested that the shortened telomere length in the brain may be an early event in MeHg-induced CNS toxicity, and the level of aMT6s in urine may serve as an early-warning biomarker for MeHg-induced CNS damage.
甲基汞（MeHg）是一种全球性污染物，已证实对中枢神经系统（CNS）具有毒性作用。然而，低剂量甲基汞暴露后中枢神经系统损伤的早期事件和早期预警生物标志物仍然缺乏。本研究旨在探讨亚慢性低剂量甲基汞暴露是否会对大鼠脑端粒长度、血清褪黑素及其尿代谢产物6-硫酸氧褪黑素（aMT6s）产生不利影响。16只雄性Sprague Dawley大鼠分为两组。第一组为对照组。在第二组中，大鼠以0.1 mg/kg/天的剂量通过灌胃暴露于甲基汞3个月。本研究表明，甲基汞暴露导致学习和记忆能力受损，海马神经元数量略有减少且神经元排列不规则。它还显著加速了大脑皮层、海马和下丘脑的端粒缩短。此外，甲基汞暴露降低了血清褪黑素和尿中aMT6s的水平，部分原因是抑制了大脑中5-羟色胺（5-HT）的合成，但促进了褪黑素催化酶AANAT和ASMT 的表达。重要的是，甲基汞暴露后脑端粒长度与MT和aMT6s呈正相关。这些结果表明，脑端粒长度缩短可能是甲基汞诱导的中枢神经系统毒性的早期事件，尿中aMT6s水平可能作为甲基汞诱导的中枢神经系统损伤的早期预警生物标志物。
