Department of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229, United States; Rhodes College, Department of Psychology, 2000 North Parkway, Memphis, TN 38112, United States.
Department of Pediatrics, University of Cincinnati College of Medicine, Division of Neurology, Cincinnati Children's Research Foundation, Cincinnati, OH 45229, United States; Virginia Department of Forensic Science, 700 North Fifth St, Richmond, VA 23219, United States.
Neurotoxicol Teratol. 2018 May-Jun;67:50-64. doi: 10.1016/j.ntt.2018.04.001. Epub 2018 Apr 7.
Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES households experience more stress and are more likely to be exposed to environmental neurotoxins such as lead (Pb) and manganese (Mn) than children in higher SES households. Co-exposure to stress, Pb, and Mn during early development may increase the risk of central nervous system dysfunction compared with unexposed children. To investigate the potential interaction of these factors, Sprague-Dawley rats were bred, and litters born in-house were culled on postnatal day (P)1 to 6 males and 6 females. One male and female within each litter were assigned to one of the following groups: 0 (vehicle), 10 mg/kg Pb, 100 mg/kg Mn, or 10 mg/kg Pb + 100 mg/kg Mn (PbMn), water gavage, and handled only from P4-28 with half the litters reared in cages with standard bedding (29 litters) and half with no bedding (Barren; 27 litters). Mn and PbMn groups had decreased anxiety, reduced acoustic startle, initial open-field hypoactivity, increased activity following (+)-methamphetamine, deficits in egocentric learning in the Cincinnati water maze (CWM), and deficits in latent inhibition conditioning. Pb increased anxiety and reduced open-field activity. Barren-reared rats had decreased anxiety, CWM deficits, increased startle, and initial open-field hyperactivity. Mn, PbMn, Pb Barren-reared groups had impaired Morris water maze performance. Pb altered neostriatal serotonin and norepinephrine, Mn increased hippocampal serotonin in males, Mn + Barren-rearing increased neostriatal serotonin, and Barren-rearing decreased neostriatal dopamine in males. At the doses used here, most effects were in the Mn and PbMn groups. Few interactions between Mn, Pb, and rearing stress were found, indicating that the interaction of these three variables is not as impactful as hypothesized.
发育应激，包括低社会经济地位（SES），可导致下丘脑-垂体-肾上腺轴失调，并导致应激反应的长期变化。SES 较低家庭的儿童经历更多的压力，并且比 SES 较高家庭的儿童更容易接触到环境神经毒素，如铅（Pb）和锰（Mn）。在早期发育过程中同时暴露于应激、Pb 和 Mn 可能会增加中枢神经系统功能障碍的风险，比未暴露的儿童更高。为了研究这些因素的潜在相互作用，饲养了 Sprague-Dawley 大鼠，并在产后第 1 天至第 6 天（P）时对室内出生的幼崽进行雄性和雌性的选择性淘汰。每窝中的一只雄性和雌性被分配到以下组之一：0（载体）、10mg/kg Pb、100mg/kg Mn 或 10mg/kg Pb+100mg/kg Mn（PbMn）、水灌胃，仅从 P4-28 开始处理，一半的幼崽在标准床上用品笼中饲养（29 窝），一半没有床上用品（贫瘠；27 窝）。Mn 和 PbMn 组的焦虑减少，听觉惊吓减少，初始开放式场活动减少，+ - 甲基苯丙胺后活动增加，辛辛那提水迷宫（CWM）中的自我中心学习缺陷以及潜伏抑制调节的缺陷。Pb 增加了焦虑并减少了开放式场活动。贫瘠饲养的大鼠焦虑减少，CWM 缺陷，惊吓增加，初始开放式场过度活跃。Mn、PbMn、Pb 贫瘠饲养组的 Morris 水迷宫表现受损。Pb 改变了新纹状体中的 5-羟色胺和去甲肾上腺素，Mn 增加了雄性海马体中的 5-羟色胺，Mn+贫瘠饲养增加了新纹状体中的 5-羟色胺，贫瘠饲养减少了雄性新纹状体中的多巴胺。在使用的剂量下，大多数影响发生在 Mn 和 PbMn 组中。Mn、Pb 和育雏应激之间很少发现相互作用，表明这三个变量的相互作用并不像假设的那样具有影响力。
