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蓝斑对环境毒物的摄取:神经退行性、脱髓鞘和精神疾病的潜在触发因素。

Uptake of environmental toxicants by the locus ceruleus: a potential trigger for neurodegenerative, demyelinating and psychiatric disorders.

作者信息

Pamphlett Roger

机构信息

The Stacey Motor Neuron Disease Laboratory, Department of Pathology, Sydney Medical School, The University of Sydney, Australia.

出版信息

Med Hypotheses. 2014 Jan;82(1):97-104. doi: 10.1016/j.mehy.2013.11.016. Epub 2013 Nov 21.

Abstract

BACKGROUND

Damage to the locus ceruleus, with a subsequent decrease of CNS noradrenaline, occurs in a wide range of neurodegenerative, demyelinating and psychiatric disorders. The cause of the initial locus ceruleus damage remains unknown. Recently, inorganic mercury was found to enter human locus ceruleus neurons selectively. This has led to the formulation of a new hypothesis as to the cause of these disorders.

HYPOTHESIS

Toxicants enter locus ceruleus neurons selectively, aided by the extensive exposure these neurons have to CNS capillaries, as well as by stressors that upregulate locus ceruleus activity. The resulting noradrenaline dysfunction affects a wide range of CNS cells and can trigger a number of neurodegenerative (Alzheimer's, Parkinson's and motor neuron disease), demyelinating (multiple sclerosis), and psychiatric (major depression and bipolar disorder) conditions.

CONCLUSIONS

This hypothesis proposes that environmental toxicants entering the locus ceruleus can give rise to a variety of CNS disorders. Proposals are made for experiments to gain further evidence for this hypothesis. If it is shown that toxicants in the locus ceruleus are responsible for these conditions, attempts can be made to prevent the toxicant exposures or to remove the toxicants from the nervous system.

摘要

背景

蓝斑受损以及随后中枢神经系统去甲肾上腺素减少,发生在多种神经退行性、脱髓鞘和精神疾病中。蓝斑最初受损的原因尚不清楚。最近,发现无机汞可选择性地进入人类蓝斑神经元。这导致了关于这些疾病病因的新假说的形成。

假说

毒物在这些神经元广泛暴露于中枢神经系统毛细血管以及上调蓝斑活动的应激源的辅助下,选择性地进入蓝斑神经元。由此产生的去甲肾上腺素功能障碍会影响多种中枢神经系统细胞,并可引发一些神经退行性疾病(阿尔茨海默病、帕金森病和运动神经元病)、脱髓鞘疾病(多发性硬化症)以及精神疾病(重度抑郁症和双相情感障碍)。

结论

该假说提出,进入蓝斑的环境毒物可引发多种中枢神经系统疾病。提出了进行实验以进一步证明该假说的建议。如果能证明蓝斑中的毒物是这些疾病的病因,就可以尝试预防毒物暴露或从神经系统中清除毒物。

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