Slotkin Theodore A, Seidler Frederic J
Department of Pharmacology and Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710, USA.
Brain Res Dev Brain Res. 2005 Aug 8;158(1-2):115-9. doi: 10.1016/j.devbrainres.2005.06.008.
Fetal or neonatal exposure to chlorpyrifos (CPF) or related organophosphate pesticides leads to abnormalities of brain cell development, synaptic function, and behavior. Recent studies in rats indicate profound effects on serotonin (5HT) systems that originate during CPF exposure and that are still present at 2 months posttreatment in the young adult. To determine if these changes are permanent, we administered 1 mg/kg of CPF daily to neonatal rats on postnatal days 1-4, a regimen devoid of systemic toxicity, and examined 5HT synaptic markers at 5 months of age: radioligand binding to 5HT1A and 5HT2 receptors and to the 5HT transporter. There were global elevations in all three synaptic proteins, with pronounced sex selectivity (effects on males>females) and a regional hierarchy of effects, viz. striatum>midbrain approximately brainstem>cerebral cortex. Because there is a normal sex disparity for 5HT synaptic proteins, with females having higher values than males, the increase caused by CPF exposure in males completely eliminated this difference. Our findings at 5 months of age replicate those seen in young adulthood and strongly suggest that the effects of neonatal CPF exposure on 5HT systems are permanent.
胎儿或新生儿接触毒死蜱（CPF）或相关有机磷农药会导致脑细胞发育、突触功能和行为异常。最近对大鼠的研究表明，CPF暴露期间起源且在年轻成年大鼠治疗后2个月仍存在的血清素（5HT）系统受到深远影响。为了确定这些变化是否是永久性的，我们在出生后第1 - 4天每天给新生大鼠施用1 mg/kg的CPF，该方案无全身毒性，并在5个月大时检查5HT突触标记物：与5HT1A和5HT2受体以及5HT转运体的放射性配体结合。所有三种突触蛋白均有整体升高，具有明显的性别选择性（对雄性的影响大于雌性）和区域效应层次，即纹状体>中脑≈脑干>大脑皮层。由于5HT突触蛋白存在正常的性别差异，雌性的值高于雄性，CPF暴露对雄性造成的增加完全消除了这种差异。我们在5个月大时的发现重复了在年轻成年期观察到的结果，并强烈表明新生儿CPF暴露对5HT系统的影响是永久性的。
