Yavuz Yavuz, Ozen Deniz Oyku, Erol Zehra Yagmur, Goren Habibe, Yilmaz Bayram
Department of Physiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
Department of Physiology, Faculty of Medicine, Yeditepe University, Istanbul, Turkey.
Environ Pollut. 2023 May 1;324:121366. doi: 10.1016/j.envpol.2023.121366. Epub 2023 Feb 27.
There is increasing concern about the effects of endocrine disrupting chemicals (EDCs) on human health. Recently, some EDCs are suggested to affect energy metabolism leading to increased risk of obesity. Obesogenic effects of some EDCs on adipogenesis have been reported, however, there is no study examining their potential actions on the brain circuits controlling feeding and metabolism. We have investigated effects of tributyltin (TBT) and dichlorodiphenyltrichloroethane (p,p'-DDT) on electrical activity on dorsomedial hypothalamic leptin receptor neurons (DMH), morphological adaptations in neuronal anatomy of DMH, locomotion, and anxiety-like behaviors in mice. Twenty-three Lep-Cre transgenic mice were intracranially injected with GFP virus. Control animals received intraperitoneal corn oil alone while group 2 and 3 received TBT (25 μg/kg) and p,p'-DDT (2 mg/kg) for one month. Locomotor activity and anxiety-like behavior of the animals were determined by open field test. Electrophysiological effects of TBT and p,p'-DDT on DMH neurons were determined by patch clamp method. Neuronal anatomy was determined by confocal microscopy. Spontaneous firing frequency of DMH neurons of TBT group of mice was significantly higher than both p,p'-DDT and control groups (p < 0.01). TBT and p,p'-DDT significantly decreased frequency of the spontaneous inhibitory post-synaptic currents to DMH neurons compared to the control group (p < 0.05). The time spent in the center and the number of entrances to the center by the TBT-administered mice were significantly lower than other groups (p < 0.01). The total distance traveled and mean speed of the control group of mice were significantly higher than the p,p'-DDT- and TBT-administered animals (p < 0.0001). c-Fos activity of the p,p'-DDT- and TBT-administered animals were significantly elevated compared to the control group (p < 0.001), while no change in the number of dendritic spines were observed. In conclusion, this study demonstrates that exposure to TBT and p,p'-DDT alters electrical activity in DMH neurons and behavioral state in mice.
人们越来越关注内分泌干扰化学物质（EDC）对人类健康的影响。最近，有研究表明某些EDC会影响能量代谢，从而增加肥胖风险。虽然已有报道称某些EDC对脂肪生成有致肥胖作用，但尚无研究探讨它们对控制进食和代谢的脑回路的潜在作用。我们研究了三丁基锡（TBT）和二氯二苯三氯乙烷（p,p'-DDT）对小鼠下丘脑背内侧瘦素受体神经元（DMH）电活动、DMH神经元解剖结构的形态适应、运动及焦虑样行为的影响。23只Lep-Cre转基因小鼠经颅内注射绿色荧光蛋白病毒。对照组动物仅腹腔注射玉米油，而第2组和第3组分别接受TBT（25μg/kg）和p,p'-DDT（2mg/kg）处理1个月。通过旷场试验测定动物的运动活动和焦虑样行为。采用膜片钳技术测定TBT和p,p'-DDT对DMH神经元的电生理效应。通过共聚焦显微镜确定神经元解剖结构。TBT组小鼠DMH神经元的自发放电频率显著高于p,p'-DDT组和对照组（p<0.01）。与对照组相比，TBT和p,p'-DDT显著降低了DMH神经元自发放电性抑制性突触后电流的频率（p<0.05）。TBT处理组小鼠在旷场中央区域停留的时间和进入中央区域的次数显著低于其他组（p<0.01）。对照组小鼠的总移动距离和平均速度显著高于p,p'-DDT处理组和TBT处理组动物（p<0.0001）。与对照组相比，p,p'-DDT处理组和TBT处理组动物的c-Fos活性显著升高（p<0.001），而树突棘数量未观察到变化。总之，本研究表明，暴露于TBT和p,p'-DDT会改变小鼠DMH神经元的电活动和行为状态。
