Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy.
Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy.
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脑吲哚胺 2,3-双加氧酶的激活导致慢性颞叶癫痫大鼠癫痫相关的抑郁样行为
DOI：
10.1186/1742-2094-11-41
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发表时间：
2014-03-04
影响因子：
9.3
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Xie W;Cai L;Yu Y;Gao L;Xiao L;He Q;Ren Z;Liu Y
抑郁症最常被诊断为颞叶癫痫（TLE）患者，但这种关联的机制仍不清楚。在这项研究中，我们报告吲哚胺2，3-双加氧酶1（IDO 1），色氨酸代谢的限速酶，在癫痫相关的抑郁样行为中起着关键作用。匹罗卡品癫痫持续状态后发生慢性癫痫的大鼠表现出一系列与抑郁样行为一致的发作间期障碍。采用味觉偏爱试验和强迫游泳试验检测抑郁行为的变化;采用实时荧光定量PCR检测脑组织IL-1β、IL-6和IDO 1的表达;采用液相色谱-质谱联用技术检测脑组织犬尿氨酸/色氨酸和5-羟色胺/色氨酸比值。采用口服米诺环素或皮下注射1-甲基色氨酸（1-MT）抑制IDO 1表达。我们观察到慢性TLE大鼠IL-1β和IL-6表达的诱导，其进一步诱导海马IDO 1表达的上调。IDO 1的上调随后增加了海马中的犬尿氨酸/色氨酸比率并降低了5-羟色胺/色氨酸比率，这有助于癫痫相关的抑郁样行为。IDO 1激活的阻断阻止了抑郁样行为的发展，但未能影响自发性癫痫发作。这种效果通过抗炎四环素衍生物米诺环素间接实现，或通过IDO拮抗剂1-MT直接实现，其使犬尿氨酸/色氨酸和5-羟色胺/色氨酸比率正常化。脑IDO 1活性在具有癫痫相关抑郁样行为的癫痫大鼠中起关键作用。
Depression has most often been diagnosed in patients with temporal lobe epilepsy (TLE), but the mechanism underlying this association remains unclear. In this study, we report that indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in epilepsy-associated depressive-like behavior. Rats which develop chronic epilepsy following pilocarpine status epilepticus exhibited a set of interictal disorders consistent with depressive-like behavior. Changes of depressive behavior were examined by taste preference test and forced swim test; brain IL-1β, IL-6 and IDO1 expression were quantified using real-time reverse transcriptase PCR; brain kynurenine/tryptophan and serotonin/tryptophan ratios were analyzed by liquid chromatography-mass spectrometry. Oral gavage of minocycline or subcutaneous injection of 1-methyltryptophan (1-MT) were used to inhibite IDO1 expression. We observed the induction of IL-1β and IL-6 expression in rats with chronic TLE, which further induced the upregulation of IDO1 expression in the hippocampus. The upregulation of IDO1 subsequently increased the kynurenine/tryptophan ratio and decreased the serotonin/tryptophan ratio in the hippocampus, which contributed to epilepsy-associated depressive-like behavior. The blockade of IDO1 activation prevented the development of depressive-like behavior but failed to influence spontaneous seizures. This effect was achieved either indirectly, through the anti-inflammatory tetracycline derivative minocycline, or directly, through the IDO antagonist 1-MT, which normalizes kynurenine/tryptophan and serotonin/tryptophan ratios. Brain IDO1 activity plays a key role in epileptic rats with epilepsy-associated depressive-like behavior.
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DOI：
10.1016/j.jchromb.2012.04.030
发表时间：
2012-06-01
影响因子：
3
作者：
Moeller, Marisa;Du Preez, Jan L.;Harvey, Brian H.
通讯作者：
Harvey, Brian H.
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影响因子：
6.1
作者：
Mazarati AM;Shin D;Kwon YS;Bragin A;Pineda E;Tio D;Taylor AN;Sankar R
通讯作者：
Sankar R
影响因子：
9.9
作者：
Martinez, Ashley;Finegersh, Andrey;Theodore, William H.
通讯作者：
Theodore, William H.
影响因子：
15.9
作者：
Kim, Hyangin;Chen, Lucy;Mao, Jianren
通讯作者：
Mao, Jianren
DOI：
10.1016/s0006-291x(05)80225-6
发表时间：
1991-04-30
影响因子：
3.1
作者：
MINAMI, M;KURAISHI, Y;SATOH, M
通讯作者：
SATOH, M