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

BMC Neuroscience

Tatyana Strekalova⁵  Raymond Cespuglio⁴  Galia V Pavlova¹  Alexander V Revishchin¹  Dmitry Malin³  Harry WM Steinbusch⁵  Brandon H Cline² 

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

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

Others  :  1141008
DOI  :  10.1186/1471-2202-13-110

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

【 摘 要 】

Background

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.

Results

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.

Conclusions

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.

【 授权许可】

   
2012 Cline et al.; licensee BioMed Central Ltd.

【 图 表 】

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