Comorbidity between epilepsy and depression: role of hippocampal interleukin-1beta.
Comorbidity between epilepsy and depression: role of hippocampal interleukin-1beta.
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DOI：
10.1016/j.nbd.2009.11.001
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发表时间：
2010-02
影响因子：
6.1
通讯作者：
Sankar R
中科院分区：
文献类型：
--
作者：
Mazarati AM;Pineda E;Shin D;Tio D;Taylor AN;Sankar R
抑郁症是颞叶癫痫(TLE)的常见共病，但其发病机制尚不清楚，缺乏有效的治疗方法。海马区白介素1β(IL-1β)信号的增强可能是TLE和临床抑郁症的一个机制因素。我们研究了在匹罗卡品癫痫持续状态(SE)后形成的Wistar大鼠TLE和抑郁共病的动物模型中，药物阻断海马白介素1受体是否具有抗抑郁作用。在SE后的动物中，抑郁状态的特征是行为上相当于快感缺乏和绝望；下丘脑-垂体-肾上腺皮质轴调节失调；中缝-海马5-羟色胺能传递受损。人重组白介素1受体拮抗剂(IL-1ra)持续两周的双侧海马区注射改善了幼稚大鼠的所有抑郁损害，但不改变自发发作频率，也不影响正常参数。这些发现提示癫痫相关性抑郁与海马区IL-1β有关，并为IL-1β阻滞剂治疗癫痫相关抑郁提供了理论依据。
Depression is a frequent comorbidity of temporal lobe epilepsy (TLE); however its mechanisms remain poorly understood and effective therapies are lacking. Augmentation of hippocampal interleukin-1β (IL-1β) signaling may be a mechanistic factor of both TLE and clinical depression. We examined whether pharmacological blockade of hippocampal interleukin-1 receptor exerts antidepressant effects in an animal model of comorbidity between TLE and depression, which developed in Wistar rats following pilocarpine status epilepticus (SE). In post-SE animals, depression-like state was characterized by behavioral equivalents of anhedonia and despair; dysregulation of the hypothalamo-pituitary-adrenocortical axis; compromised raphe-hippocampal serotonergic transmission. Two-week long bilateral intrahippocampal infusion of human recombinant Interleukin-1 Receptor antagonist (IL-1ra) improved all of the examined depressive impairments, without modifying spontaneous seizure frequency and without affecting normal parameters in naïve rats. These findings implicate hippocampal IL-1β in epilepsy-associated depression, and provide a rationale for the introduction of IL-1β blockers in the treatment of depression in TLE.
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实验性颞叶癫痫中血浆皮质酮水平升高和抑郁行为。
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：
10.5
作者：
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通讯作者：
REIS, DJ
影响因子：
9.9
作者：
Gilliam, F. G.;Maton, B. M.;Kuzniecky, R. I.
通讯作者：
Kuzniecky, R. I.
影响因子：
10.6
作者：
Kanner, AM
通讯作者：
Kanner, AM
影响因子：
3.4
作者：
Konsman, J. P.;Veeneman, J.;Dantzer, R.
通讯作者：
Dantzer, R.