Zhang Chao, Xu Qinghua, Xiao Xia, Li Weihao, Kang Qiang, Zhang Xiong, Wang Tinghua, Li Yan
Department of Women and Child Health, School of Public Health, Kunming Medical University, Kunming, China.
Department of Pediatrics, Weifang Yidu Central Hospital, Shandong, China.
Front Neurosci. 2018 Sep 4;12:615. doi: 10.3389/fnins.2018.00615. eCollection 2018.
Pyrethroids have been widely used in residential and agricultural areas. However, little is known about the effects of prenatal exposure to deltamethrin on cognition in early development of offspring. In this study, the effects of prenatal exposure to deltamethrin on learning and memory abilities, -methyl-D-aspartate receptor (NMDAR) subunits, brain derived neurotrophic factor (BDNF), Tyrosine kinase B (TrkB) receptor, and phosphorylated cAMP response element binding protein (pCREB) in the hippocampus of offspring rats were investigated. Groups each of six female SD rats, as F0-generation, were administered with deltamethrin (0, 0.54, 1.35, and 2.7, 9 mg/kg), or memantine (10 mg/kg), or co-administered with deltamethrin (9 mg/kg) and memantine (10 mg/kg) daily by gavage during pregnancy. The learning and memory ability was evaluated using Morris water maze (MWM) task on postnatal day 21. The expression of NMDAR (GluN1, GluN2A, and GluN2B), BDNF, pTrkB/TrkB, and pCREB/CREB in hippocampus were assessed with western blotting. Prenatal exposure to a relatively low dose of deltamethrin (2.7, 1.35, and 0.54 mg/kg) had no impact on learning and memory abilities or the expression of NMDAR, BDNF, pTrkB, and pCREB in the hippocampus of the exposed offspring. The group treated with 9 mg/kg deltamethrin showed impaired cognitive abilities and decreased expression levels of GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB in the hippocampus. However, the declined cognitive ability were ameliorated by memantine treatment with increased GluN1, GluN2A, GluN2B, BDNF, pCREB/CREB, and pTrkB/TrkB expression in the hippocampus. Prenatal exposure to a relatively high does of deltamethrin (9 mg/kg) alters cognition in offsprings and that this cognitive dysfunction can be ameliorated by memantine treatment. Moreover, NMDAR/BDNF signaling may be associated with the effects of prenatal exposure to deltamethrin on cognitive ability in offspring.
拟除虫菊酯已在居民区和农业领域广泛使用。然而，关于产前接触溴氰菊酯对后代早期发育阶段认知的影响，我们却知之甚少。在本研究中，我们调查了产前接触溴氰菊酯对仔鼠海马体学习记忆能力、N-甲基-D-天冬氨酸受体（NMDAR）亚基、脑源性神经营养因子（BDNF）、酪氨酸激酶B（TrkB）受体以及磷酸化环磷腺苷反应元件结合蛋白（pCREB）的影响。将每组六只雌性SD大鼠作为F0代，在孕期通过灌胃方式每日给予溴氰菊酯（0、0.54、1.35、2.7、9毫克/千克）、美金刚（10毫克/千克），或同时给予溴氰菊酯（9毫克/千克）和美金刚（10毫克/千克）。在出生后第21天，使用莫里斯水迷宫（MWM）任务评估学习记忆能力。通过蛋白质免疫印迹法评估海马体中NMDAR（GluN1、GluN2A和GluN2B）、BDNF、pTrkB/TrkB以及pCREB/CREB的表达。产前接触相对低剂量的溴氰菊酯（2.7、1.35和0.54毫克/千克）对暴露后代的学习记忆能力以及海马体中NMDAR、BDNF、pTrkB和pCREB的表达没有影响。给予9毫克/千克溴氰菊酯处理的组表现出认知能力受损，海马体中GluN1、GluN2A、GluN2B、BDNF、pCREB/CREB和pTrkB/TrkB的表达水平降低。然而，美金刚治疗改善了认知能力下降的情况，海马体中GluN1、GluN2A、GluN2B、BDNF、pCREB/CREB和pTrkB/TrkB的表达增加。产前接触相对高剂量的溴氰菊酯（9毫克/千克）会改变后代的认知，而美金刚治疗可改善这种认知功能障碍。此外，NMDAR/BDNF信号通路可能与产前接触溴氰菊酯对后代认知能力的影响有关。
