The neurotropic parasite Toxoplasma gondii increases dopamine metabolism.
The neurotropic parasite Toxoplasma gondii increases dopamine metabolism.
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DOI：
10.1371/journal.pone.0023866
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
McConkey GA
中科院分区：
文献类型：
--
作者：
Prandovszky E;Gaskell E;Martin H;Dubey JP;Webster JP;McConkey GA
高度流行的弓形虫会操纵宿主的行为。在受感染的啮齿动物中，行为变化增加了寄生虫传播回其最终宿主猫的可能性，这是寄生虫完成生命周期的重要步骤。导致宿主行为改变的机制尚不清楚，但已发表的两项证据表明，寄生虫改变了神经递质信号转导：用于治疗精神疾病的药物（特别是多巴胺拮抗剂）破坏了寄生虫诱导的行为改变，以及鉴定了寄生虫基因组中编码的酪氨酸羟化酶。在本研究中，弓形虫感染哺乳动物多巴胺能细胞后，K+诱导的多巴胺释放水平增加数倍，感染细胞数量与多巴胺释放量直接相关。用多巴胺抗体对感染小鼠的脑切片进行免疫染色，显示出强烈的寄生虫包囊染色。基于这些分析，弓形虫协调了神经细胞中多巴胺代谢的显著增加。酪氨酸羟化酶是多巴胺合成的限速酶，在脑组织的细胞内组织囊肿中也发现了针对寄生虫编码的酪氨酸羟化酶的抗体。这些观察结果为寄生虫诱导的行为改变提供了一种机制。观察到的对多巴胺代谢的影响也可能与解释弓形虫感染人类心理行为改变的报告有关。
The highly prevalent parasite Toxoplasma gondii manipulates its host's behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasite's life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense staining of encysted parasites. Based on these analyses, T. gondii orchestrates a significant increase in dopamine metabolism in neural cells. Tyrosine hydroxylase, the rate-limiting enzyme for dopamine synthesis, was also found in intracellular tissue cysts in brain tissue with antibodies specific for the parasite-encoded tyrosine hydroxylase. These observations provide a mechanism for parasite-induced behavioral changes. The observed effects on dopamine metabolism could also be relevant in interpreting reports of psychobehavioral changes in toxoplasmosis-infected humans.
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DOI：
10.1073/pnas.91.2.509
发表时间：
1994-01-18
影响因子：
11.1
作者：
SCHWAB, JC;BECKERS, CJM;JOINER, KA
通讯作者：
JOINER, KA
影响因子：
2.7
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影响因子：
4
作者：
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影响因子：
3.1
作者：
Silva, NM;Rodrigues, CV;Gazzinelli, RT
通讯作者：
Gazzinelli, RT
影响因子：
6.6
作者：
Torrey, E. Fuller;Bartko, John J.;Yolken, Robert H.
通讯作者：
Yolken, Robert H.