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Related Experiment Video

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Meridianins Inhibit GSK3β In Vivo and Improve Behavioral Alterations Induced by Chronic Stress.

Anna Sancho-Balsells1,2,3, Esther García-García1,2,3, Francesca Flotta1,2,3

  • 1Departament de Biomedicina, Facultat de Medicina, Institut de Neurociències (UBneuro), University of Barcelona, 08036 Barcelona, Spain.

Marine Drugs
|October 26, 2022
PubMed
Summary

Meridianins, natural compounds, show promise for treating major depression disorder (MDD) by inhibiting GSK3β without side effects. Chronic stress in mice improved behaviorally after meridianin treatment.

Keywords:
AktGSK3βGluR1PKAPKCmemorysynaptic activity

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Marine Biology

Background:

  • Major depression disorder (MDD) is a severe mental health condition with chronic stress as a key risk factor.
  • Current treatments for MDD are ineffective in approximately 30% of patients.
  • Glycogen synthase kinase 3 beta (GSK3β) inhibitors show therapeutic potential but often cause off-target effects.

Purpose of the Study:

  • To investigate the therapeutic potential of meridianins, natural alkaloids from Antarctic marine ascidians, for stress-related disorders.
  • To evaluate meridianins' ability to inhibit GSK3β activity in brain regions affected by stress.
  • To assess meridianins' impact on signaling pathways and synaptic activity, and their efficacy in a chronic stress mouse model.

Main Methods:

  • Administered meridianins intracerebroventricularly to rodents to assess GSK3β inhibition in relevant brain areas.
  • Analyzed changes in key signaling pathways (Akt, PKA, PKC, GluR1) in the prefrontal cortex and hippocampus.
  • Evaluated synaptic activity in hippocampal subfields (CA1, CA3).
  • Treated mice subjected to unpredictable mild chronic stress (CUMS) with meridianins and assessed behavioral improvements.

Main Results:

  • Meridianins successfully inhibited GSK3β in brain regions associated with stress.
  • Observed significant alterations in Akt, PKA, PKC, and GluR1 signaling pathways.
  • Demonstrated increased synaptic activity in the CA1 hippocampal subfield.
  • Meridianins significantly ameliorated behavioral deficits induced by chronic unpredictable mild stress (CUMS) in mice.

Conclusions:

  • Meridianins inhibit GSK3β effectively in vivo without apparent neurotoxicity or off-target effects.
  • Meridianins modulate key signaling pathways and enhance synaptic plasticity in the hippocampus.
  • Meridianins show therapeutic promise for treating stress-related disorders, including major depression disorder (MDD).