McDaniel Katherine L, Beasley Tracey E, Oshiro Wendy M, Huffstickler Mitchell, Moser Virginia C, Herr David W
Neurological & Endocrine Toxicology Branch, Public Health & Integrated Toxicology Division, Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States of America.
Neurological & Endocrine Toxicology Branch, Public Health & Integrated Toxicology Division, Center for Public Health and Environmental Assessment, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, United States of America.
Neurotoxicol Teratol. 2022 May-Jun;91:107088. doi: 10.1016/j.ntt.2022.107088. Epub 2022 Mar 10.
Manganese (Mn), an element that naturally occurs in the environment, has been shown to produce neurotoxic effects on the developing young when levels exceed physiological requirements. To evaluate the effects of this chemical in combination with non-chemical factors pregnant Long-Evans rats were treated with 0, 2, or 4 mg/mL Mn in their drinking water from gestational day (GD) 7 to postnatal day (PND) 22. Half of the dams received a variable stress protocol from GD13 to PND9, that included restraint, small cage with reduced bedding, exposure to predator odor, intermittent intervals of white noise, lights on for 24 h, intermittent intervals of lights on during dark cycle and cages with grid floors and reduced bedding. One male and one female offspring from each litter were tested to assess untrained behavior. Ultrasonic vocalizations (USV) were recorded from PND13 pups while they were isolated from the litter. Locomotor activity (MA) was measured in figure-eight mazes at PND 17, 29, and 79 (different set of rats at each time point). Social approach (SA) was tested at PND48. Acoustic startle response (ASR) and pre-pulse inhibition (PPI) were measured starting at PND58. At PND53 a sweetness preference for a chocolate flavored milk solution was assessed. There were sex related differences on several parameters for the USVs. There was also a Mn by stress by sex interaction with the females from the 4 mg/mL stressed dams having more frequency modulated (FM) call elements than the 4 mg/mL non-stressed group. There was an effect of Mn on motor activity but only at PND29 with the 2 mg/mL group having higher counts than the 0 mg/mL group. The social approach test showed sex differences for both the habituation and test phase. There was an effect of Mn, with the 4 mg/mL males having a greater preference for the stimulus rat than did the 0 mg/mL males. There was also a stress by sex interaction. The ASR and PPI had only a sex effect. Thus, with only the FM call elements having a Mn by stress effect, and the PND29 MA and SA preference index having a Mn effect but at different doses requires further investigation.
锰（Mn）是一种自然存在于环境中的元素，当含量超过生理需求时，已被证明会对发育中的幼体产生神经毒性作用。为了评估这种化学物质与非化学因素联合作用的影响，从妊娠第7天（GD）至出生后第22天（PND），给怀孕的Long-Evans大鼠饮用含0、2或4mg/mL锰的水。一半的母鼠从GD13至PND9接受可变应激方案，包括束缚、垫料减少的小笼子、暴露于捕食者气味、间歇性白噪声、24小时光照、黑暗周期中间歇性光照以及带网格地板和减少垫料的笼子。从每窝中选取一只雄性和一只雌性后代进行测试，以评估未经训练的行为。在PND13幼崽与同窝隔离时记录超声波发声（USV）。在PND 17、29和79（每个时间点使用不同组的大鼠）在数字八迷宫中测量运动活动（MA）。在PND48测试社交接近（SA）。从PND58开始测量听觉惊吓反应（ASR）和前脉冲抑制（PPI）。在PND53评估对巧克力味牛奶溶液的甜味偏好。在USV的几个参数上存在性别相关差异。在4mg/mL应激母鼠的雌性后代中，也存在锰与应激和性别的相互作用，其具有比4mg/mL非应激组更多的频率调制（FM）叫声元素。锰对运动活动有影响，但仅在PND29时，2mg/mL组的计数高于0mg/mL组。社交接近测试在习惯化和测试阶段均显示出性别差异。锰有影响，4mg/mL的雄性比0mg/mL的雄性对刺激大鼠有更大的偏好。也存在应激与性别的相互作用。ASR和PPI仅具有性别效应。因此，只有FM叫声元素具有锰与应激的效应，而PND29的MA和SA偏好指数具有锰效应但剂量不同，这需要进一步研究。
