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Oleanolic acid decreases SGK1 in the hippocampus in corticosterone-induced mice

Shu-Qi Dong1, Shuang-Shuang Wang1, Ji-Xiao Zhu2

  • 1Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.

Steroids
|June 3, 2019
PubMed

Insights

Oleanolic acid shows antidepressant effects by down-regulating serine/threonine-protein kinase 1 (SGK1) in stress-induced depression models. Direct inhibition of SGK1 did not yield similar antidepressant outcomes.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Biology

Background:

  • Chronic stress and depression are linked to altered stress response pathways.
  • Serine/threonine-protein kinase 1 (SGK1) plays a role in the cellular stress response.
  • Oleanolic acid has demonstrated antidepressant-like effects in previous studies.

Purpose of the Study:

  • To investigate the role of SGK1 in the antidepressant-like effects of oleanolic acid.
  • To explore the molecular mechanisms underlying oleanolic acid's action in a depression model.

Main Methods:

  • Induction of depression-like behavior in mice using long-term corticosterone (CORT) injection.
  • Administration of oleanolic acid and an SGK1 inhibitor (GSK650394).
  • Assessment of behavioral changes, SGK1 levels, brain-derived neurotrophic factor (BDNF) signaling, and neuronal spine density.

Main Results:

  • Oleanolic acid treatment improved depression-like behaviors, increasing sucrose preference and reducing immobility time.
  • Oleanolic acid decreased SGK1 expression and activated BDNF-AKT/mTOR signaling in the hippocampus.
  • Direct inhibition of SGK1 with GSK650394 did not alter behaviors, GR levels, BDNF signaling, or neuronal spine density.

Conclusions:

  • Oleanolic acid exerts antidepressant-like effects potentially through SGK1 down-regulation.
  • Direct pharmacological inhibition of SGK1 is not sufficient for treating depression in this model.
  • The findings suggest a complex role for SGK1 in depression and highlight oleanolic acid as a potential therapeutic agent.
Keywords:
Brain-derived neurotrophic factor (BDNF)DepressionGSK650394Oleanolic acidSGK1

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