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

BMC Neuroscience

Research Article

Galia V Pavlova¹  Alexander V Revishchin²  Brandon H Cline³  Raymond Cespuglio⁴  Harry WM Steinbusch⁵  Tatyana Strekalova⁵  Dmitry Malin⁶ 

[1] Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov str, 119334, Moscow, Russia;Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaya str. 8, 125315, Moscow, Russia;Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov str, 119334, Moscow, Russia;Interdisciplinary Center for Neurosciences, Heidelberg University, and Institute for Neuroanatomy, University Clinic Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany;Lyon1, Faculty of Medicine, Claude Bernard University, EA 4170, Av. Rockefeller 8, 69373, Lyon, CEDEX 08, France;School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Universiteitssingel 40, 6229 ER, Maastricht, NL, Netherlands;University of Wisconsin, Carbon Cancer Center, WIMR 3016, 1111 Highland Ave, 53705, Madison, WI, USA;Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaya str. 8, 125315, Moscow, Russia;

关键词: Dicholine succinate;    Insulin-like receptor;    Insulin growth factor 2;    Hippocampus;    Stress-induced anhedonia;    Mouse;   

DOI  :  10.1186/1471-2202-13-110

 received in 2012-03-26, accepted in 2012-09-14,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundA 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.ResultsAdministration 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.ConclusionsOur 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.

【 授权许可】

Unknown   
© Cline et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.