Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling.
Taenia larvae possess distinct acetylcholinesterase profiles with implications for host cholinergic signalling.
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DOI：
10.1371/journal.pntd.0008966
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发表时间：
2020-12
影响因子：
3.8
通讯作者：
Raimondo JV
中科院分区：
文献类型：
--
作者：
de Lange A;Prodjinotho UF;Tomes H;Hagen J;Jacobs BA;Smith K;Horsnell W;Sikasunge C;Hockman D;Selkirk ME;Prazeres da Costa C;Raimondo JV
猪带绦虫和粗头绦虫的幼虫感染人类的中枢神经系统。脑内的猪带绦虫幼虫引起脑囊虫病，这是全球成人获得性癫痫的主要原因。关于绦虫衍生产品如何调节宿主神经和免疫信号传导，了解相对较少。乙酰胆碱酯酶是一类分解乙酰胆碱的酶，由寄生蠕虫产生，以帮助它们在宿主中生存。乙酰胆碱是人类神经和免疫系统中的重要信号分子，对皮层网络的兴奋性具有强大的调节作用。因此，重要的是要确定是否绦虫衍生的乙酰胆碱酯酶可能会改变宿主神经元胆碱能信号。在这里，我们利用多种技术来配置文件乙酰胆碱酯酶活性在不同的提取物中的两个粗头绦虫和猪带绦虫幼虫。我们发现，这两个物种的幼虫含有大量的乙酰胆碱酯酶活性。然而，乙酰胆碱酯酶活性较低，猪带绦虫粗头绦虫幼虫相比。此外，虽然我们观察到乙酰胆碱酯酶活性的所有部分的带绦虫粗头绦虫幼虫，包括在膜表面上和排泄/分泌的提取物，我们不能确定乙酰胆碱酯酶的膜表面上或在排泄/分泌的提取物的带绦虫幼虫。生物信息学分析显示，与人类同源序列相比，猪带绦虫乙酰胆碱酯酶的功能蛋白质结构域保守。最后，使用大鼠海马脑片培养物的全细胞膜片钳记录，我们证明了带绦虫幼虫衍生的乙酰胆碱酯酶可以在一定浓度下分解乙酰胆碱，从而诱导神经元信号传导的变化。总之，这些研究结果突出的可能性，带绦虫幼虫乙酰胆碱酯酶可以干扰胆碱能信号在主机，可能有助于在脑囊虫病的发病机制。寄生虫猪带绦虫幼虫感染人类神经系统是世界范围内获得性癫痫的重要原因。尽管如此，神经囊尾蚴病癫痫发生的确切细胞和分子机制仍不清楚。乙酰胆碱酯酶是由蠕虫寄生虫广泛产生的酶家族。这些酶促进乙酰胆碱的分解，乙酰胆碱也是人类神经系统中的主要神经递质。如果T.由于绦虫幼虫产生乙酰胆碱酯酶，这可能会破坏宿主的胆碱能信号传导，这反过来可能导致癫痫发作和癫痫。因此，我们着手研究乙酰胆碱酯酶在T。猪囊尾蚴幼虫，以及粗头带绦虫幼虫，一种在神经囊尾蚴病研究中常用作模式寄生虫的物种。我们发现T. crassiceps和T.猪带绦虫幼虫产生具有实质活性的乙酰胆碱酯酶，并且猪带绦虫乙酰胆碱酯酶中的功能性蛋白质结构域与人乙酰胆碱酯酶的功能性蛋白质结构域非常相似。我们进一步证明，这些寄生虫的产品中的乙酰胆碱酯酶活性足以在体外脑切片模型中诱导神经元信号传导变化的浓度下分解乙酰胆碱。这项研究提供的证据表明，带绦虫幼虫产生乙酰胆碱酯酶，这些可以潜在地干扰胆碱能信号在主机，并有助于在脑囊虫病的发病机制。
Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis. Infection of the human nervous system with larvae of the parasite Taenia solium is a significant cause of acquired epilepsy worldwide. Despite this, the precise cellular and molecular mechanisms underlying epileptogenesis in neurocysticercosis remain unclear. Acetylcholinesterases are a family of enzymes widely produced by helminthic parasites. These enzymes facilitate the breakdown of acetylcholine, which is also a major neurotransmitter in the human nervous system. If T. solium larvae produce acetylcholinesterases, this could potentially disrupt host cholinergic signalling, which may in turn contribute to seizures and epilepsy. We therefore set out to investigate the presence and activity of acetylcholinesterases in T. solium larvae, as well as in Taenia crassiceps larvae, a species commonly used as a model parasite in neurocysticercosis research. We found that both T. crassiceps and T. solium larvae produce acetylcholinesterases with substantial activity and that the functional protein domains in the Taenia solium acetylcholinesterases have great similarity to those of human acetylcholinesterases. We further demonstrate that the acetylcholinesterase activity in the products of these parasites is sufficient to break down acetylcholine at a concentration which induces changes in neuronal signalling in an ex vivo brain slice model. This study provides evidence that Taenia larvae produce acetylcholinesterases and that these can potentially interfere with cholinergic signalling in the host and contribute to pathogenesis in neurocysticercosis.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
6.7
作者：
Darby M;Schnoeller C;Vira A;Culley FJ;Bobat S;Logan E;Kirstein F;Wess J;Cunningham AF;Brombacher F;Selkirk ME;Horsnell WG
通讯作者：
Horsnell WG
影响因子：
5.5
作者：
COLE, AE;NICOLL, RA
通讯作者：
NICOLL, RA
影响因子：
--
作者：
CORDNER, SM;FYSH, RR;WHITAKER, SJ
通讯作者：
WHITAKER, SJ
DOI：
10.1111/j.1748-1716.1968.tb04099.x
发表时间：
1968-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
ERANKO, O;KOUVALAINEN, K;TAKKI, S
通讯作者：
TAKKI, S