Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus.
Prenatal Deltamethrin Exposure-Induced Cognitive Impairment in Offspring Is Ameliorated by Memantine Through NMDAR/BDNF Signaling in Hippocampus.
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美金刚通过海马中的 NMDAR/BDNF 信号传导改善了产前溴氰菊酯暴露引起的后代认知障碍。
DOI：
10.3389/fnins.2018.00615
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发表时间：
2018
影响因子：
4.3
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Zhang C;Xu Q;Xiao X;Li W;Kang Q;Zhang X;Wang T;Li Y
背景：拟除虫菊酯已广泛用于住宅和农业领域。然而，关于产前暴露于溴氰菊酯对后代早期发育中认知的影响知之甚少。在这项研究中，研究了产前暴露于溴氰菊酯对子代大鼠学习和记忆能力、海马中N-甲基-D-天冬氨酸受体（NMDAR）亚单位、脑源性神经营养因子（BDNF）、酪氨酸激酶B（Trk B）受体和磷酸化cAMP反应元件结合蛋白（pCREB）的影响。实验方法：每组6只雌性SD大鼠（作为F0代）在妊娠期间每日通过灌胃给予溴氰菊酯（0、0.54、1.35和2.7、9 mg/kg）或美金刚（10 mg/kg），或与溴氰菊酯（9 mg/kg）和美金刚（10 mg/kg）联合给药。于生后第21天采用Morris水迷宫（MWM）任务评价大鼠的学习记忆能力。采用免疫印迹法检测海马NMDAR（GluN 1、GluN 2A和GluN 2B）、BDNF、pTrkB/TrkB和pCREB/CREB的表达。结果如下：产前暴露于相对低剂量的溴氰菊酯（2.7、1.35和0.54 mg/kg）对暴露后代的学习和记忆能力或海马中NMDAR、BDNF、pTrkB和pCREB的表达无影响。9 mg/kg溴氰菊酯给药组显示认知能力受损，海马中GluN 1、GluN 2A、GluN 2B、BDNF、pCREB/CREB和pTrkB/TrkB的表达水平降低。然而，通过增加海马中GluN 1、GluN 2A、GluN 2B、BDNF、pCREB/CREB和pTrkB/TrkB的表达，美金刚治疗改善了下降的认知能力。结论和启示：产前暴露于相对较高剂量的溴氰菊酯（9 mg/kg）会改变后代的认知功能，这种认知功能障碍可以通过美金刚治疗得到改善。此外，NMDAR/BDNF信号可能与产前暴露于溴氰菊酯对后代认知能力的影响有关。
Background: 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, N-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. Experimental Approaches: 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. Results: 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. Conclusion and Implications: 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.
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影响因子：
16.2
作者：
Park, Hyungju;Popescu, Andrei;Poo, Mu-ming
通讯作者：
Poo, Mu-ming
影响因子：
3.4
作者：
Guo, Xin;Chen, Zheng-Hua;Wang, Gao-Hua
通讯作者：
Wang, Gao-Hua
影响因子：
4.2
作者：
Babot, Zoila;Vilaro, M. Teresa;Sunol, Cristina
通讯作者：
Sunol, Cristina
影响因子：
2.7
作者：
Hansen MRH;Jørs E;Lander F;Condarco G;Debes F;Bustillos NT;Schlünssen V
通讯作者：
Schlünssen V
影响因子：
2.5
作者：
Aziz, MH;Agrawal, AK;Seth, PK
通讯作者：
Seth, PK