Glucocorticoid hormone (cortisol) affects axonal transport in human cortex neurons but shows resistance in Alzheimer's disease
Glucocorticoid hormone (cortisol) affects axonal transport in human cortex neurons but shows resistance in Alzheimer's disease
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DOI：
10.1038/sj.bjp.0705995
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发表时间：
2004-11-01
影响因子：
7.3
通讯作者：
Swaab, D
中科院分区：
文献类型：
--
作者：
Dai, JP;Buijs, R;Swaab, D
1组织对糖皮质激素敏感性的改变与包括神经系统疾病在内的多种病理状态有关。在本研究中，使用一种新的体外死后人脑切片追踪方法，我们证明了皮质醇，一种人体主要的糖皮质激素，皮质醇影响4名阿尔茨海默病（AD）患者和4名非痴呆对照者皮层神经元的轴突运输。2皮质醇似乎影响前额叶皮层（PFC）和颞叶皮层（TC）的轴突运输在30、60、120和240 μ g/dl（~ 1 × 10 - 3）的浓度下，TC神经元需要更高剂量的皮质醇以实现与在AD患者的PFC神经元中获得的类似的轴突运输效应。在相对较低的收缩时，PFC切片中轴突运输的最大效应（E-max）达到（30 - 120 mug dl（-1）），而在TC切片中，只有在相对较高的浓度下才能达到最大效应（120 - 240 μ g dl（-1））。4对于来自非痴呆老年受试者的PFC和TC切片，低剂量皮质醇（30 - 60 μ g dl（-1））对轴突运输的作用足以达到最大效果，而超过60 μ g dl（-1）的皮质醇水平主要抑制轴突转运。5这些结果表明，被认为导致许多常见人类疾病发病机制的糖皮质激素抵抗可能存在于AD脑中，并在神经病理机制和痴呆中起重要作用。
1 The changes of tissue sensitivity to glucocorticoids are associated with many pathological states including neurological diseases. In the present study, using a novel in vitro post-mortem tracing method on human brain slices, we demonstrated that cortisol, a major glucocorticoid hormone in humans, affected axonal transport both in the cortex neurons in four Alzheimer's disease ( AD) patients and four nondemented controls.2 Cortisol appeared to affect axonal transport of prefrontal cortex (PFC) and temporal cortex (TC) neurons in AD patients and controls in a dose-dependent way at concentrations of 30, 60, 120 and 240 mug dl(-1).3 Higher doses of cortisol were needed for TC neurons to achieve a similar axonal transport effect as obtained in PFC neurons in AD patients. The maximum effect (E-max) on axonal transport was achieved in PFC slices at relatively low contraction (30 - 120 mug dl(-1)), while in TC slices, a maximum effect was only reached at relatively high concentrations (120 - 240 mug dl(-1)).4 For PFC and TC slices from nondemented aging subjects, lower doses of cortisol (30 - 60 mug dl(-1)) on axonal transport were sufficient to achieve the maximum effect as compared to those used in AD brain slices, while levels of more than 60 mug dl(-1) of cortisol mostly depressed axonal transport.5 These results suggest that glucocorticoid resistance, which is thought to contribute to the pathogenesis of a number of common human disorders, may exist in AD brains and play an important role in neuropathological mechanisms and dementia.