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一种用于研究急性铁离子暴露对本体感觉神经元影响的无脊椎动物模型。

An invertebrate model in examining the effect of acute ferric iron exposure on proprioceptive neurons.

作者信息

Wagers Mikaela L, Starks Ashley, Abul-Khoudoud Maya O, Ahmed Sufia M, Alhamdani Abraham W, Ashley Clair, Bidros Patrick C, Bledsoe Constance O, Bolton Kayli E, Capili Jerone G, Henning Jamie N, Ison Bethany J, Moon Madison, Phe Panhavuth, Stonecipher Samuel B, Taylor Isabelle N, Turner Logan T, West Aaron K, Cooper Robin L

机构信息

Department of Biology, University of Kentucky, Lexington 40506, KY, USA.

Department of Biology, University of Kentucky, Lexington 40506, KY, USA.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2023 Apr;266:109558. doi: 10.1016/j.cbpc.2023.109558. Epub 2023 Jan 28.

Abstract

Iron is an essential element for plant and animal life and is found in soil, fresh waters and marine waters. The Fe ion is a vital prosthetic group and cofactor to mitochondrial electron transport complexes and numerous proteins involved in normal functioning. Despite its importance to life-sustaining processes, overexposure results in toxicity. For example, ferric iron (Fe) accumulation in the mammalian central nervous system is associated with various neurological disorders. Although current literature addresses the long-term effects of Fe overload, fewer studies exist examining the effects of acute exposure. Using the blue crab (Callinectes sapidus), we investigate the effects of acute Fe overload on proprioception within the propodite-dactylopodite (PD) nerve. For proprioceptive studies, 10- and 20-mM ferric chloride and ferric ammonium citrate solutions were used at 5- and 20- min exposure times. Exposure to 20 mM concentrations of ferric chloride and ferric ammonium citrate reduced excitability in proprioceptive neurons. Thus, Fe likely blocks stretch-activated channels or voltage-gated Na channels. The depressive effects of Fe are partly reversible following saline washout, indicating cells are not acutely damaged. Gadolinium (GdCl, 1 and 10 mM) was used to examine the effects of an additional trivalent ion comparator. Gd depressed PD nerve compound action potential amplitude while increasing the compound action potential duration. This study is relevant in demonstrating the dose-dependent effects of acute Fe and Gd exposure on proprioception and provides a model system to further investigate the mechanisms by which metals act on the nervous system.

摘要

铁是动植物生命所必需的元素,存在于土壤、淡水和海水中。铁离子是线粒体电子传递复合物以及许多参与正常功能的蛋白质的重要辅基和辅助因子。尽管它对维持生命的过程很重要,但过度暴露会导致毒性。例如,哺乳动物中枢神经系统中铁(Fe³⁺)的积累与各种神经疾病有关。虽然目前的文献涉及铁过载的长期影响,但研究急性暴露影响的研究较少。我们使用蓝蟹(Callinectes sapidus)来研究急性铁过载对掌节 - 指节(PD)神经内本体感觉的影响。对于本体感觉研究,使用了10 mM和20 mM的氯化铁和柠檬酸铁铵溶液,暴露时间分别为5分钟和20分钟。暴露于20 mM浓度的氯化铁和柠檬酸铁铵会降低本体感觉神经元的兴奋性。因此,铁可能会阻断牵张激活通道或电压门控钠通道。用生理盐水冲洗后,铁的抑制作用部分可逆,这表明细胞没有受到急性损伤。使用钆(GdCl₃,1 mM和10 mM)来研究另一种三价离子对照物的影响。钆会降低PD神经复合动作电位的幅度,同时增加复合动作电位的持续时间。这项研究证明了急性铁和钆暴露对本体感觉的剂量依赖性影响,并提供了一个模型系统来进一步研究金属作用于神经系统的机制。

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