Interdisciplinary Center for Neurosciences, Heidelberg University, and Institute for Neuroanatomy, University Clinic Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
BMC Neurosci. 2012 Sep 18;13:110. doi: 10.1186/1471-2202-13-110.
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.
多项流行病学研究已经确立了胰岛素抵抗与抑郁症患病率之间的联系。研究发现，抑郁症的发生先于糖尿病的发生，并假设与外周和中枢胰岛素受体的遗传性相关不足有关。最近，二氢胆碱琥珀酸盐，一种神经元胰岛素受体的敏化剂，被证明可以刺激胰岛素依赖性 H2O2 的产生，从而增强神经元中胰岛素受体的自身磷酸化作用。因此，这种机制可以成为提高胰岛素信号的新靶点。
在应激程序开始前，给 CD1 小鼠腹腔内注射 DS（25mg/kg/天）7 天，可减轻蔗糖测试中定义的快感缺失表现和强迫游泳测试中的行为绝望。二氢胆碱琥珀酸盐的治疗可降低应激小鼠在暗/光箱范式中的焦虑评分，防止应激诱导的在跳下回避测试中长时程情景记忆的下降和海马 IGF2 的基因表达。
我们的数据表明，二氢胆碱琥珀酸盐具有抗抑郁样作用，这可能是通过上调海马 IGF2 的表达介导的，并提示神经元胰岛素受体参与应激诱导的抑郁综合征的发病机制。
