Animal Laboratory Center, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Prosthodontics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
FASEB J. 2021 Jan;35(1):e21273. doi: 10.1096/fj.202001290R.
Numerous studies have confirmed that prenatal or early postnatal exposure to pesticides can lead to functional deficits in the developing brain. This study aimed to investigate whether combined exposure to paraquat (PQ) and maneb (MB) during puberty could cause permanent toxic effects in the neural system of rats. In addition, the neuroprotective function of taurine (T) and its possible mechanism were investigated. Rats were administered PQ + MB intragastrically for 12 continuous weeks, while taurine dissolved in water was fed to the rats for 24 continuous weeks. In the behavioral tests, the rats' trajectories became complex, and the reaction latencies and mistake frequencies increased. Significant changes were found in the hippocampal neurons of the PQ + MB groups but not in the taurine treatment groups. PQ + MB stimulated cAMP to reduce the production of protein kinase A (PKA) and inhibited the activation of other elements, such as brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB), phospho-CREB (p-CREB), immediate-early genes (IEGs)Arc, and c-Fos. Importantly, taurine regulated the level of cAMP and the expression of the abovementioned proteins. Together, our findings implied that adolescent exposure to PQ + MB may impact the behavior and cognitive function of rats via the cAMP-PKA-CREB signaling pathway, while taurine may in turn exert neuroprotection by diminishing these impacts.
许多研究证实，产前或产后早期接触农药会导致发育中大脑的功能缺陷。本研究旨在探讨青春期同时暴露于百草枯（PQ）和代森锰（MB）是否会对大鼠神经系统造成永久性毒性影响。此外，还研究了牛磺酸（T）的神经保护功能及其可能的机制。大鼠连续 12 周经胃内给予 PQ+MB，同时连续 24 周给予牛磺酸溶解在水中的溶液。在行为测试中，大鼠的轨迹变得复杂，反应潜伏期和错误频率增加。在 PQ+MB 组的海马神经元中发现了明显的变化，但在牛磺酸治疗组中没有发现变化。PQ+MB 刺激 cAMP 减少蛋白激酶 A（PKA）的产生，并抑制其他元素的激活，如脑源性神经营养因子（BDNF）、cAMP 反应元件结合蛋白（CREB）、磷酸化 CREB（p-CREB）、即刻早期基因（IEGs）Arc 和 c-Fos。重要的是，牛磺酸调节 cAMP 的水平和上述蛋白的表达。总之，我们的研究结果表明，青春期暴露于 PQ+MB 可能通过 cAMP-PKA-CREB 信号通路影响大鼠的行为和认知功能，而牛磺酸可能通过减轻这些影响发挥神经保护作用。
