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海洛因成瘾者成人神经发生阶段神经元前体细胞的改变。

Alterations of neuronal precursor cells in stages of human adult neurogenesis in heroin addicts.

作者信息

Bayer Ronny, Franke Heike, Ficker Christoph, Richter Monique, Lessig Rüdiger, Büttner Andreas, Weber Marco

机构信息

Institute of Legal Medicine, University of Leipzig, D-04103 Leipzig, Germany.

Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, D-04107 Leipzig, Germany.

出版信息

Drug Alcohol Depend. 2015 Nov 1;156:139-149. doi: 10.1016/j.drugalcdep.2015.09.005. Epub 2015 Sep 15.

Abstract

BACKGROUND

Adult neurogenesis has been shown to occur throughout life and different brain pathologies were demonstrated to be associated with altered neurogenesis. Here, an impact of heroin addiction on neurogenesis in humans is hypothesised.

METHODS

Post mortem hippocampal specimens of drug addicts with known heroin abuse and a group of non-addictive control subjects were analysed, using antibodies indicating different stages of neurogenesis. The subgranular zone of the dentate gyrus was examined qualitatively and quantitatively.

RESULTS

The data indicate (i) a decreased number of neural precursor cells, (ii) accompanied by low rates of proliferation and (iii) a marked loss of dendritic trees in targeting cells in heroin fatalities. (iv) The age-dependent increase of differentiating cells in the healthy controls was not observed in the addicts. Additionally, double immunofluorescence labelling indicated the precursor nature of Musashi-1 positive cells in the human subgranular zone of the dentate gyrus.

CONCLUSIONS

Present data firstly demonstrate the influence of drug addiction with known heroin abuse on different developmental stages of progenitors in the dentate gyrus. The patterns of antibody staining suggest a distinct inhibition of neurogenesis at the stage of neural precursor cells and revealed morphological changes in targeting cells in cases of heroin addicts as compared to healthy controls. These alterations could be considerable for memory and cognitive deficits as well as addictive behaviour in chronic drug abusers and may give rise to specific pro-neurogenic therapies.

摘要

背景

已证实成体神经发生在整个生命过程中都会发生,并且不同的脑部病变与神经发生改变有关。在此,我们假设海洛因成瘾对人类神经发生有影响。

方法

使用指示神经发生不同阶段的抗体,对已知有海洛因滥用史的吸毒者和一组非成瘾对照受试者的死后海马标本进行分析。对齿状回的颗粒下区进行定性和定量检查。

结果

数据表明,在海洛因致死病例中,(i)神经前体细胞数量减少,(ii)伴随着增殖率降低,(iii)靶向细胞的树突明显丢失。(iv)在吸毒者中未观察到健康对照中随年龄增长的分化细胞增加。此外,双重免疫荧光标记表明在人类齿状回颗粒下区中Musashi-1阳性细胞的前体性质。

结论

目前的数据首次证明了已知海洛因滥用的药物成瘾对齿状回祖细胞不同发育阶段的影响。抗体染色模式表明在神经前体细胞阶段神经发生受到明显抑制,并且与健康对照相比,揭示了海洛因成瘾者靶向细胞的形态变化。这些改变对于慢性药物滥用者的记忆和认知缺陷以及成瘾行为可能相当重要,并可能引发特定的促神经发生疗法。

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