Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance.
Systemic Copper Disorders Influence the Olfactory Function in Adult Rats: Roles of Altered Adult Neurogenesis and Neurochemical Imbalance.
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DOI：
10.3390/biom11091315
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发表时间：
2021-09-06
期刊：
影响因子：
5.5
通讯作者：
Cannon J
中科院分区：
文献类型：
--
作者：
Adamson SX;Zheng W;Agim ZS;Du S;Fleming S;Shannahan J;Cannon J
系统铜（Cu）稳态的破坏是神经退行性疾病的基础，其早期症状包括嗅觉功能障碍。本研究探讨了铜稳态失调对嗅觉功能，成年神经发生和神经化学平衡的影响。采用限铜饲料加腹腔注射的方法建立大鼠铜缺乏（CuD）和铜超负荷（CuO）模型。分别注入Cu螯合剂（四硫代钼酸铵）和过量Cu。CuD降低了嗅球（OB）、脑室下区（SVZ）、吻侧迁移流（RMS）和纹状体中的铜水平，而CuO增加了这些区域中的铜水平。埋丸试验显示CuD和CuO均延长了暴露食物的潜伏期。CuD增加神经增殖和干细胞在SVZ和新分化的神经元在OB，而CuO引起相反的改变，这表明“开关”型功能的铜在调节成人神经发生。CuO使OB的GABA增加，而CuD和CuO均使嗅觉相关脑区的DOPAC、HVA、5-HT和DA周转率降低。在这两种条件下，观察到在测试的大脑区域中的铜转运和储存蛋白的mRNA表达的改变。总之，结果支持系统性铜代谢障碍和嗅觉功能障碍之间的关联。具体而言，改变成人神经发生沿着SVZ-RMS-OB途径和神经化学失衡可能是因素，可能有助于嗅觉功能障碍。
Disrupted systemic copper (Cu) homeostasis underlies neurodegenerative diseases with early symptoms including olfactory dysfunction. This study investigated the impact of Cu dyshomeostasis on olfactory function, adult neurogenesis, and neurochemical balance. Models of Cu deficiency (CuD) and Cu overload (CuO) were established by feeding adult rats with Cu-restricted diets plus ip. injection of a Cu chelator (ammonium tetrathiomolybdate) and excess Cu, respectively. CuD reduced Cu levels in the olfactory bulb (OB), subventricular zone (SVZ), rostral migratory stream (RMS), and striatum, while CuO increased Cu levels in these areas. The buried pellet test revealed both CuD and CuO prolonged the latency to uncover food. CuD increased neural proliferation and stem cells in the SVZ and newly differentiated neurons in the OB, whereas CuO caused opposite alterations, suggesting a “switch”-type function of Cu in regulating adult neurogenesis. CuO increased GABA in the OB, while both CuD and CuO reduced DOPAC, HVA, 5-HT and the DA turnover rate in olfactory-associated brain regions. Altered mRNA expression of Cu transport and storage proteins in tested brain areas were observed under both conditions. Together, results support an association between systemic Cu dyshomeostasis and olfactory dysfunction. Specifically, altered adult neurogenesis along the SVZ-RMS-OB pathway and neurochemical imbalance could be the factors that may contribute to olfactory dysfunction.
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