The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2
1 Interdisciplinary Center for Neurosciences, Heidelberg University, and Institute for Neuroanatomy, University Clinic Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany
2 School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL, 6229 ER, Maastricht, Netherlands
3 University of Wisconsin, Carbon Cancer Center, WIMR 3016, 1111 Highland Ave, Madison, WI, 53705, USA
4 Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaya str. 8, 125315, Moscow, Russia
5 Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov str, Moscow, 119334, Russia
6 Claude Bernard University, Lyon1, Faculty of Medicine, EA 4170, Av. Rockefeller 8, 69373, Lyon, CEDEX 08, France
BMC Neuroscience 2012, 13:110 doi:10.1186/1471-2202-13-110Published: 18 September 2012
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.