The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2.
The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2.
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DOI：
10.1186/1471-2202-13-110
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发表时间：
2012-09-18
期刊：
影响因子：
2.4
通讯作者：
Strekalova T
中科院分区：
文献类型：
--
作者：
Cline BH;Steinbusch HW;Malin D;Revishchin AV;Pavlova GV;Cespuglio R;Strekalova T
许多流行病学研究已经确定了胰岛素抵抗和抑郁症的流行之间的联系。抑郁症的发生被发现先于糖尿病的发病，并被假设与遗传性的外周和中枢胰岛素受体相互关联的不足有关。最近，神经元胰岛素受体的增敏剂丁二酸地高林被证明能刺激线粒体呼吸链上胰岛素依赖性过氧化氢的产生，从而增强神经元上胰岛素受体的自磷酸化。因此，这一机制可能成为胰岛素信号上调的新靶点。CD1小鼠在应激程序开始前连续7天给予DS(25 mg/kg/天)，可减少蔗糖试验中的快感丧失和强迫游泳试验中的行为绝望。丁二酸地高辛治疗可降低应激小鼠在暗/灯箱实验中的焦虑分数，阻止应激引起的跳台回避实验中长时语境记忆和海马区IGF2基因表达的下降。提示丁二酸地高辛具有抗抑郁作用，其机制可能与上调海马区IGF2的表达有关，并提示神经元胰岛素受体参与应激性抑郁综合征的发病机制。
A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling. Administration of DS (25 mg/kg/day, intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2. Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.
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影响因子：
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