The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2

• Main Authors: Cline Brandon H, Steinbusch Harry WM, Malin Dmitry, Revishchin Alexander V, Pavlova Galia V, Cespuglio Raymond, Strekalova Tatyana
• Format: Article
• Language: English
• Published: BMC 2012-09-01
• Series: BMC Neuroscience
• Subjects: Dicholine succinate; Insulin-like receptor; Insulin growth factor 2; Hippocampus; Stress-induced anhedonia; Mouse
• Online Access: http://www.biomedcentral.com/1471-2202/13/110

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p>