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

AbstractBACKGROUND:
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.
AuthorsBrandon H Cline, Harry W M Steinbusch, Dmitry Malin, Alexander V Revishchin, Galia V Pavlova, Raymond Cespuglio, Tatyana Strekalova
JournalBMC neuroscience (BMC Neurosci) Vol. 13 Pg. 110 (Sep 18 2012) ISSN: 1471-2202 [Electronic] England
PMID22989159 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antidepressive Agents
  • IGF2 protein, mouse
  • Insulin-Like Growth Factor II
  • Receptor, Insulin
  • Succinylcholine
  • Imipramine
Topics
  • Animals
  • Antidepressive Agents (pharmacology, therapeutic use)
  • Anxiety (complications, drug therapy, psychology)
  • Depression (complications, drug therapy, psychology)
  • Disease Models, Animal
  • Hippocampus (drug effects, metabolism)
  • Imipramine (pharmacology, therapeutic use)
  • Insulin-Like Growth Factor II (biosynthesis, physiology)
  • Male
  • Memory Disorders (complications, drug therapy, psychology)
  • Mice
  • Mice, Inbred ICR
  • Neurons (metabolism)
  • Receptor, Insulin (metabolism)
  • Stress, Psychological (complications, drug therapy, psychology)
  • Succinylcholine (pharmacology, therapeutic use)
  • Up-Regulation (drug effects)

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