Effects of copper metabolism on neurological functions in Wistar and Wilson's disease model rats
Effects of copper metabolism on neurological functions in Wistar and Wilson's disease model rats
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DOI：
10.1016/j.bbrc.2006.08.139
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发表时间：
2006-10-27
影响因子：
3.1
通讯作者：
Suzuki, Keiichiro
中科院分区：
文献类型：
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作者：
Fujiwara, Noriko;Iso, Hiroyuki;Suzuki, Keiichiro
本研究通过对Wistar和Long-Evans Cinnamon（LEC）大鼠的旷场、声惊吓反射、前脉冲抑制（PPI）和梭箱回避学习实验，比较了口服铜或铜螯合剂D-青霉胺对大鼠行为功能的影响。与Wistar大鼠相比，所有LEC大鼠，无论治疗，表现出更高的运动活动，减少习惯惊吓反应或更低的PPI。除延髓外，LEC大鼠各脑区铜含量均显著低于Wistar大鼠。此外，LEC大鼠纹状体和中脑核内去甲肾上腺素含量低于Wistar大鼠，多巴胺和5-羟色胺含量高于Wistar大鼠。虽然铜的补充并没有影响脑铜含量，它降低了PPI在Wistar和LEC大鼠。与此相反，D-青霉胺补充降低脑铜含量和自发活动，并加强惊吓幅度只在Wistar大鼠。这些发现表明，铜稳态的失衡影响单胺代谢和行为功能。(c)2006年爱思唯尔公司All rights reserved.
Behavioral functions of Wistar and Long-Evans Cinnamon (LEC) rats, Wilson's disease animal model, were compared by measuring the open-field, acoustic startle reflex and prepulse inhibition (PPI), and shuttle-box avoidance learning tests with or without oral supplementation,with copper or D-penicillamine, copper chelator. All of the LEC rats, irrespective of the treatment, exhibited higher locomotor activity, a decreased habituation to startle response or a lower PPI, compared with Wistar rats. The copper content of all brain regions examined, except for the medulla oblongata of LEC rats, was significantly lower than those in Wistar rats. Besides, in the region of the striatum and the nucleus accumbens of the LEC rats, lower content of norepinephrine, and higher content of dopamine and serotonin were observed compared with Wistar rats. Although copper supplementation did not affect the brain copper content, it reduced the PPI in both Wistar and LEC rats. In contrast, D-penicillamine supplementation decreased both the brain copper content and locomotor activity, and enhanced the startle amplitude only in Wistar rats. These findings suggest that an imbalance in copper homeostasis affects monoamine metabolism and behavioral functions. (c) 2006 Elsevier Inc. All rights reserved.