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

Brandon H. Cline, Harry W. M. Steinbusch, Dmitry Malin, Alexander V. Revishchin, Galia V. Pavlova, Raymond Cespuglio, Tatyana Strekalova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

45 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Pages (from-to)110
JournalBMC Neuroscience
Volume13
DOIs
Publication statusPublished - 18 Sep 2012

Keywords

  • Dicholine succinate
  • Insulin-like receptor
  • Insulin growth factor 2
  • Hippocampus
  • Stress-induced anhedonia
  • Mouse

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