脂多糖（LPS）在阿尔茨海默氏病（AD）大脑的新皮质神经元中积累，并损害人类神经元-胶质原代共培养物中的转录。,Frontiers in Aging Neuroscience

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脂多糖（LPS）在阿尔茨海默氏病（AD）大脑的新皮质神经元中积累，并损害人类神经元-胶质原代共培养物中的转录。
Frontiers in Aging Neuroscience ( IF 4.1 ) Pub Date : 2018-01-10 , DOI: 10.3389/fnagi.2017.00407
Yuhai Zhao _{1,

2} , Lin Cong _{1,

3} , Walter J Lukiw _{1,

3,

4,

5}

Affiliation

几个独立的实验室最近报告了在受阿尔茨海默氏病（AD）影响的大脑组织中检测细菌核酸序列或细菌衍生的神经毒素，例如高度炎症性脂多糖（LPS）。这些细菌神经毒素是否源自胃肠道（GI）微生物组，可能的脑部微生物组或某些休眠的病理微生物组目前尚不清楚。先前的研究表明，促炎性LPS与受AD影响的脑细胞核的共定位表明，这种神经毒素可能与支持炎性神经变性和稳态基因表达失败的遗传毒性事件有关。在此报告中，我们提供了证据，证明在零星的广告中，LPS逐渐积累在神经元实质中，并且似乎优先与神经元核的周围缔合。使用[α-32P]-尿苷三磷酸掺入新合成的总RNA中的常规转录研究进一步表明，与LPS孵育的初次共培养中的人神经胶质（HNG）细胞显示出明显降低的DNA转录产物输出。这些研究表明，AD LPS可能会损害正常的脑细胞功能稳态操作通常所需的神经元遗传信息的有效读取，并且可能会导致遗传信息读取的逐步中断。使用[α-32P]-尿苷三磷酸掺入新合成的总RNA中的常规转录研究进一步表明，与LPS孵育的初次共培养中的人神经胶质（HNG）细胞显示出明显降低的DNA转录产物输出。这些研究表明，AD LPS可能会损害正常的脑细胞功能稳态操作通常所需的神经元遗传信息的有效读取，并且可能会导致遗传信息读取的逐步中断。利用[α-32P]-尿苷三磷酸掺入新合成的总RNA进行的即时转录研究进一步表明，与LPS孵育的初级共培养中的人类神经胶质（HNG）细胞显示出明显降低的DNA转录产物输出。这些研究表明，AD LPS可能会损害正常的脑细胞功能稳态操作通常所需的神经元遗传信息的有效读取，并且可能会导致遗传信息读取的逐步中断。

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Lipopolysaccharide (LPS) Accumulates in Neocortical Neurons of Alzheimer's Disease (AD) Brain and Impairs Transcription in Human Neuronal-Glial Primary Co-cultures.

Several independent laboratories have recently reported the detection of bacterial nucleic acid sequences or bacterial-derived neurotoxins, such as highly inflammatory lipopolysaccharide (LPS), within Alzheimer's disease (AD) affected brain tissues. Whether these bacterial neurotoxins originate from the gastrointestinal (GI) tract microbiome, a possible brain microbiome or some dormant pathological microbiome is currently not well understood. Previous studies indicate that the co-localization of pro-inflammatory LPS with AD-affected brain cell nuclei suggests that there may be a contribution of this neurotoxin to genotoxic events that support inflammatory neurodegeneration and failure in homeostatic gene expression. In this report we provide evidence that in sporadic AD, LPS progressively accumulates in neuronal parenchyma and appears to preferentially associate with the periphery of neuronal nuclei. Run-on transcription studies utilizing [α-32P]-uridine triphosphate incorporation into newly synthesized total RNA further indicates that human neuronal-glial (HNG) cells in primary co-culture incubated with LPS exhibit significantly reduced output of DNA transcription products. These studies suggest that in AD LPS may impair the efficient readout of neuronal genetic information normally required for the homeostatic operation of brain cell function and may contribute to a progressive disruption in the read-out of genetic information.

更新日期：2019-11-01

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