Muralikrishnan Dhanasekaran, Ebadi Manuchair, Brown-Borg Holly M
Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine and Health Sciences, Grand Forks, North Dakota, USA.
Neurochem Res. 2002 Jun;27(6):457-64. doi: 10.1023/a:1019888300957.
Hypopituitary dwarf mice exhibit a heightened antioxidative capacity and live extensively longer than age-matched controls. Importantly, dwarf mice resist peripheral oxidative stress induced by paraquat, and behaviorally, they maintain cognitive function and locomotor activity at levels above those observed in old wild-type animals. We assessed monoaminergic neurotransmitters in nigrostriatal tract and cerebellum after the administration of the dopaminergic neurotoxin, MPTP. There was no significant change in mitochondrial monoamine oxidase (MAO)-B and total MAO activity in the substantia nigra and nucleus caudatus putamen of wild-type and dwarf mice. Coenzymes Q-9 and Q-10 were present in similar quantities, as were dopamine, norepinephrine, and serotonin levels in the cerebellum and nigrostriatal tract. MPTP set off tremor, hind limb abduction, and straub tail behavior and induced significant dopamine depletion in the striatum of both dwarf and normal mice. This study shows that the MAO activity and the coenzyme content of dwarf mice are similar to those of their wild-type controls and hence susceptible to MPTP-induced toxicity.
垂体功能减退的侏儒小鼠表现出更高的抗氧化能力,并且比年龄匹配的对照小鼠寿命长得多。重要的是,侏儒小鼠能抵抗百草枯诱导的外周氧化应激,而且在行为上,它们能将认知功能和运动活动维持在高于老年野生型动物所观察到的水平。我们在给予多巴胺能神经毒素MPTP后,评估了黑质纹状体通路和小脑中的单胺能神经递质。野生型和侏儒小鼠的黑质和尾状核壳核中的线粒体单胺氧化酶(MAO)-B和总MAO活性没有显著变化。辅酶Q-9和Q-10的含量相似,小脑和黑质纹状体通路中的多巴胺、去甲肾上腺素和血清素水平也相似。MPTP引发了震颤、后肢外展和斯特劳布尾行为,并在侏儒和正常小鼠的纹状体中诱导了显著的多巴胺耗竭。这项研究表明,侏儒小鼠的MAO活性和辅酶含量与其野生型对照相似,因此易受MPTP诱导的毒性影响。