Deltamethrin Exposure Inhibits Adult Hippocampal Neurogenesis and Causes Deficits in Learning and Memory in Mice
Deltamethrin Exposure Inhibits Adult Hippocampal Neurogenesis and Causes Deficits in Learning and Memory in Mice
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DOI：
10.1093/toxsci/kfaa144
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发表时间：
2020-12-01
影响因子：
3.8
通讯作者：
Richardson, Jason R.
中科院分区：
文献类型：
--
作者：
Hossain, Muhammad M.;Belkadi, Abdelmadjid;Richardson, Jason R.
学习和记忆的缺陷通常与海马神经发生的破坏有关，海马神经发生受许多过程的调节，包括前体细胞增殖、存活、迁移和向成熟神经元的分化。近年来的研究表明，成年海马齿状回（DG）中的神经元可以在功能上整合到现有的神经元回路中，并参与海马依赖的学习和记忆。在这里，我们证明了相对短期的溴氰菊酯暴露（每3天3mg/kg，持续1个月）会抑制小鼠成年海马神经发生并导致学习和记忆缺陷。采用2项独立的海马依赖行为测试、新物体识别任务和Morris水迷宫评估海马依赖认知功能。我们发现，经溴氰菊酯处理的小鼠在水迷宫中出现了严重的新物体识别和学习记忆缺陷。溴氰菊酯暴露显著降低海马DG中溴脱氧尿苷（BrdU）阳性细胞（39%）和Ki67阳性细胞（47%），表明细胞增殖降低。此外，经溴氰菊酯处理的小鼠表达巢蛋白的神经祖细胞减少44%，表达双皮质素（DCX）的减少38%，双皮质素是一种早期神经元分化标志物。此外，接触溴氰菊酯的小鼠DG中的颗粒细胞总数减少了25%。这些发现表明，相对短期暴露于溴氰菊酯会导致海马神经发生显著缺陷，这与学习和记忆受损有关。
Deficits in learning and memory are often associated with disruption of hippocampal neurogenesis, which is regulated by numerous processes, including precursor cell proliferation, survival, migration, and differentiation to mature neurons. Recent studies demonstrate that adult born neurons in the dentate gyrus (DG) in the hippocampus can functionally integrate into the existing neuronal circuitry and contribute to hippocampal-dependent learning and memory. Here, we demonstrate that relatively short-term deltamethrin exposure (3mg/kg every 3days for 1month) inhibits adult hippocampal neurogenesis and causes deficits in learning and memory in mice. Hippocampal-dependent cognitive functions were evaluated using 2 independent hippocampal-dependent behavioral tests, the novel object recognition task and Morris water maze. We found that deltamethrin-treated mice exhibited profound deficits in novel object recognition and learning and memory in water maze. Deltamethrin exposure significantly decreased bromodeoxyuridine (BrdU)-positive cells (39%) and Ki67+ cells (47%) in the DG of the hippocampus, indicating decreased cellular proliferation. In addition, deltamethrin-treated mice exhibited a 44% decrease in nestin-expressing neural progenitor cells and a 38% reduction in the expression of doublecortin (DCX), an early neuronal differentiation marker. Furthermore, deltamethrin-exposed mice exhibited a 25% reduction in total number of granule cells in the DG. These findings indicate that relatively short-term exposure to deltamethrin causes significant deficits in hippocampal neurogenesis that is associated with impaired learning and memory.