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产前暴露于汽油-乙醇混合蒸汽中会导致成年大鼠出现一些认知缺陷。

Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats.

作者信息

Oshiro W M, Beasley T E, McDaniel K L, Evansky P A, Martin S A, Moser V C, Gilbert M E, Bushnell P J

机构信息

Toxicity Assessment Division, MD B105-04, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

Environmental Public Health Division, MD B105-02, National Health Effects and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA.

出版信息

Neurotoxicol Teratol. 2015 May-Jun;49:59-73. doi: 10.1016/j.ntt.2015.04.001. Epub 2015 Apr 12.

Abstract

Developmental exposure to inhaled ethanol-gasoline fuel blends is a potential public health concern. Here we assessed cognitive functions in adult offspring of pregnant rats that were exposed to vapors of gasoline blended with a range of ethanol concentrations, including gasoline alone (E0) and gasoline with 15% or 85% ethanol (E15 and E85, respectively). Rat dams were exposed for 6.5h daily to the vapors at concentrations of 0, 3000, 6000, or 9000 ppm in inhalation chambers from gestational day (GD) 9 through 20. Cage controls (offspring of non-exposed dams that remained in the animal facility during these exposures) were also assessed in the E0 experiment, but showed no consistent differences from the offspring of air-exposed controls. Offspring were tested as adults with trace fear conditioning, Morris water maze, or appetitive operant responding. With fear conditioning, no significant effects were observed on cue or context learning. In the water maze, there were no differences in place learning or escaping to a visible platform. However, during the reference memory probe (no platform) male rats exposed prenatally to E85 vapor (6000 and 9000 ppm) failed to show a bias for the target quadrant. Across studies, females (treated and some controls) were less consistent in this measure. Males showed no differences during match-to-place learning (platform moved each day) in any experiment and females showed only transient differences in latency and path length in the E0 experiment. Similarly, no differences were observed in delayed match-to-sample operant performance of E0 males or females; thus this test was not used to evaluate effects of E15 or E85 vapors. During choice reaction time assessments (only males were tested) decision and movement times were unimpaired by any prenatal exposure, while anticipatory responses were increased by vapors of E0 (9000 ppm) and E15 (6000 and 9000 ppm), and the latter group also showed reduced accuracy. E85 vapors did not disrupt any choice reaction time measure. Finally, no response inhibition deficit was observed in a differential reinforcement of low rate (DRL) response schedule in males or females in the E15 or E85 experiments. In summary, prenatal exposure to these fuel blends produced few deficits in adult offspring on these cognitive tests. Significant effects found during a water maze probe trial and choice reaction time tests were observed at vapor concentrations of 6000 ppm or higher, a concentration that is 4-6 orders of magnitude higher than those associated with normal automotive fueling operations and garages. Similar effects were not consistently observed in a previous study of inhaled ethanol, and thus these effects cannot be attributed to the concentration of ethanol in the mixture.

摘要

孕期吸入乙醇 - 汽油混合燃料对发育的影响是一个潜在的公共卫生问题。在此,我们评估了怀孕大鼠成年后代的认知功能,这些大鼠暴露于与一系列乙醇浓度混合的汽油蒸气中,包括纯汽油(E0)以及含15%或85%乙醇的汽油(分别为E15和E85)。从妊娠第9天到第20天,将孕鼠每天6.5小时暴露于吸入舱中浓度为0、3000、6000或9000 ppm的蒸气中。在E0实验中也评估了笼养对照(未暴露孕鼠的后代,在这些暴露期间留在动物设施中),但与空气暴露对照的后代相比没有一致的差异。后代成年后通过痕迹恐惧条件反射、莫里斯水迷宫或食欲性操作性反应进行测试。在恐惧条件反射测试中,未观察到对线索或情境学习有显著影响。在水迷宫测试中,位置学习或游向可见平台方面没有差异。然而,在参考记忆探测(无平台)时,产前暴露于E85蒸气(6000和9000 ppm)的雄性大鼠未能表现出对目标象限的偏好。在所有研究中,雌性(处理组和一些对照组)在这一指标上的表现不太一致。在任何实验中,雄性在匹配位置学习(平台每天移动)期间均无差异,而在E0实验中,雌性仅在潜伏期和路径长度上有短暂差异。同样,在E0雄性或雌性的延迟匹配样本操作性表现中未观察到差异;因此该测试未用于评估E15或E85蒸气的影响。在选择反应时间评估中(仅测试了雄性),任何产前暴露均未损害决策和运动时间,而E0(9000 ppm)和E15(6000和9000 ppm)的蒸气增加了预期反应,并且后一组的准确性也降低。E85蒸气未干扰任何选择反应时间指标。最后,在E15或E85实验中,雄性或雌性在低速率差异强化(DRL)反应程序中均未观察到反应抑制缺陷。总之,产前暴露于这些燃料混合物对成年后代的这些认知测试几乎没有造成缺陷。在水迷宫探测试验和选择反应时间测试中发现的显著影响出现在蒸气浓度为6000 ppm或更高时,该浓度比与正常汽车加油操作和车库相关的浓度高4 - 6个数量级。在先前一项关于吸入乙醇的研究中未一致观察到类似影响,因此这些影响不能归因于混合物中乙醇的浓度。

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