Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.
Toxoplasma gondii actively inhibits neuronal function in chronically infected mice.
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DOI：
10.1371/journal.pone.0035516
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Budinger E
中科院分区：
文献类型：
--
作者：
Haroon F;Händel U;Angenstein F;Goldschmidt J;Kreutzmann P;Lison H;Fischer KD;Scheich H;Wetzel W;Schlüter D;Budinger E
在感染专性细胞内寄生虫刚地弓形虫后，快速复制的速殖子感染广泛的宿主细胞，包括神经元。在免疫反应的压力下，速殖子转化为复制缓慢的慢殖子，在神经元中以囊肿的形式持续存在。目前，尚不清楚弓形虫是否会改变神经元的功能活动，这可能有助于弓形虫感染小鼠和男性的行为改变。在目前的研究中，我们证明，在口腔感染弓形虫囊肿后，慢性感染的BALB/c小鼠随着时间的推移失去了对猫尿的自然恐惧，这与寄生虫在影响行为和气味感知的大脑区域的持续存在是平行的。详细的免疫组化显示，在感染的神经元中，不仅寄生囊肿，宿主细胞质和部分轴突弓形虫抗原也呈阳性，提示寄生蛋白可能直接干扰神经元功能。事实上，体外活细胞钙（Ca2+）成像研究表明，速殖子在谷氨酸刺激下主动操纵Ca2+信号，导致高反应或低反应神经元。内质网Ca2+摄取抑制剂thapsigargin的实验表明速殖子消耗内质网Ca2+储存。此外，体内研究表明，在囊肿窝藏神经元中，钾类似物铊的活性依赖性摄取减少，表明它们的功能受损。无功能神经元的比例随着时间的推移而增加。总之，慢殖子和快殖子都在功能上沉默了被感染的神经元，这可能显著地改变了宿主的行为。
Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii–infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca2+) imaging studies revealed that tachyzoites actively manipulated Ca2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host.
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影响因子：
--
作者：
Kim, Ji Yeon;Ahn, Hye-Jin;Nam, Ho-Woo
通讯作者：
Nam, Ho-Woo
影响因子：
7.4
作者：
Xie, CS;Markesbery, WR;Lovell, MA
通讯作者：
Lovell, MA
影响因子：
5.6
作者：
Stommel, EW;Seguin, R;Kasper, LH
通讯作者：
Kasper, LH
DOI：
10.1073/pnas.0608310104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Vyas, Ajai;Kim, Seon-Kyeong;Sapolsky, Robert M.
通讯作者：
Sapolsky, Robert M.
影响因子：
1.6
作者：
Hinze-Selch, Dunja;Daeubener, Walter;Wilms, Sibylle
通讯作者：
Wilms, Sibylle