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Inhaled manganese alters neurological response to toxic challenges: Implication to developmental exposures.

机译:吸入锰会改变对毒性挑战的神经反应:对发育性接触的影响。

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This dissertation investigates the interactive effects on the brain of two dopaminergic toxins, manganese and methamphetamine. Uptake of manganese from ambient sources can be highly bioavailable. Since manganese is an essential element and a neurotoxin when present in excess of biological needs, exposure to manganese from ambient sources could represent an important risk. Methamphetamine, also a neurotoxin, is an increasingly popular drug of abuse and representative of a wide array of amphetamine-type pharmaceuticals. The importance of manganese as an issue of environmental concern has recently increased because of its use as a major industrial product and to replace tetraethyl lead and MTBE as a gasoline additive. This could increase human exposures to airborne manganese. Since inhaled manganese and amphetamines target the same area of the brain, this research was designed to determine whether exposure to manganese by inhalation alters dopaminergic system responses to a subsequent exposure to methamphetamine such that dopaminergic toxicity will occur below the toxic threshold for either of the individual substances. Understanding the potential for a neurotoxic interaction between manganese aerosol and methamphetamine is highly relevant in re-evaluating both the extent to which air pollution may alter human health and the potential risks to populations using amphetamine-type drugs, with respect to neurological disease, drug addiction and neurodegeneration.; Transient inhalation manganese exposure of pregnant rats decreased striatal dopamine levels in progeny by 9%. These changes occurred following an estimated maternal absorbed dose of 2.3 mugMn and were measured in tissue collected 62 days after exposure. This same pattern of altered dopamine levels occurred in rats exposed postnatally to either manganese aerosol or methamphetamine. Prenatal exposure to manganese caused a shift in postnatal methamphetamine-induced analyte response to enhance overall dopaminergic injury by 28% from methamphetamine-alone values and 36% from control values. Summarily, prenatal manganese exposure alters normal dopaminergic response to postnatal challenges of manganese and methamphetamine. Significant effects on morphological structure and striatal axon distribution in response to prenatal manganese and postnatal methamphetamine administration are discussed.; The essentiality of manganese at all stages of development make this research critical in better understanding the neurodevelopmentally toxic action of increasing levels of ambient manganese.
机译:本文研究了两种多巴胺能毒素,锰和甲基苯丙胺对大脑的相互作用。从环境中吸收锰的生物利用率很高。由于锰是人体必需的元素和神经毒素,如果超出了生物需求,则从环境中接触锰可能会构成重大风险。甲基苯丙胺,也是一种神经毒素,是一种越来越流行的滥用药物,并代表着多种苯丙胺类药物。由于将锰用作主要工业产品并代替四乙基铅和MTBE作为汽油添加剂,因此,锰作为环境问题的重要性最近得到了提高。这可能会增加人类对空气中锰的暴露。由于吸入的锰和苯丙胺针对的是大脑的同一区域,因此本研究旨在确定通过吸入接触锰是否会改变多巴胺能系统对随后接触甲基苯丙胺的反应,从而使多巴胺能毒性低于任何一个人的毒性阈值物质。在重新评估空气污染可能改变人类健康的程度以及使用苯丙胺类药物的人群对神经系统疾病,药物成瘾的潜在风险方面,了解锰气雾剂与甲基苯丙胺之间存在神经毒性相互作用的可能性非常重要。和神经变性。怀孕大鼠的短暂吸入锰暴露使子代的纹状体多巴胺水平降低了9%。这些变化发生在母体吸收剂量估计为2.3 mugMn之后,并在暴露后62天收集的组织中测量到。在出生后暴露于锰气雾剂或甲基苯丙胺的大鼠中也发生了相同的多巴胺水平改变。产前暴露于锰导致产后甲基苯丙胺引起的分析物响应发生变化,从而使总的多巴胺能损伤比单独使用甲基苯丙胺的值增加了28%,与对照值相比增加了36%。综上所述,产前锰暴露改变了正常的多巴胺能对产后锰和甲基苯丙胺攻击的反应。讨论了响应产前锰和产后甲基苯丙胺对形态结构和纹状体轴突分布的重要影响。锰在所有开发阶段的必要性使这项研究对于更好地理解环境中锰水平升高所产生的神经发育毒性作用至关重要。

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