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Published on: January 7, 2019
γ-Oryzanol Ameliorates Depressive Behavior in Ovariectomized Mice by Regulating Hippocampal Nitric Oxide Synthase: A
Minji Kim1,2, Minseok Yoon1, Suengmok Cho3
1Division of Functional Food Research, Korea Food Research Institute, Wanju, 55365, Republic of Korea.
Scope:
Depression is a severe mental condition, common among menopausal women. γ-Oryzanol (ORY) has various biological properties; however, the effect of ORY on menopausal depression and its underlying mechanisms have not been investigated.
Methods And Results:
ORY is orally administered to ovariectomized (OVX) mice for 20 weeks. ORY administration results in lower immobility time in the tail suspension and forced swim test and increases locomotor activity in the open field test. In the primary hippocampal neurons and hippocampi of OVX mice, ORY treatment increases nitric oxide (NO) production and neuronal NO synthase (nNOS) expression. Further, the phosphorylation of extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and tropomyosin receptor kinase B, along with the expression of brain-derived neurotrophic factior (BDNF), is upregulated. These stimulatory effects of ORY are diminished by treatment with estrogen receptor β (ERβ) antagonist. ORY similarly interacts with ERβ in the molecular docking analysis. Moreover, intracerebroventricular injection of 7-nitroindazole, a nNOS inhibitor, abolishes the antidepressant effects of ORY.
Conclusions:
The results indicate that ORY attenuates depressive behavior in OVX mice by upregulating ERβ-mediated hippocampal nNOS expression and activating the ERK-CREB-BDNF signaling networks. The findings suggest that ORY is a potential therapeutic agent for attenuating menopausal depression.
Insights
γ-Oryzanol (ORY) may alleviate menopausal depression by boosting nitric oxide (NO) and activating brain pathways. This study investigated ORY
Area of Science:
- Neuroscience
- Pharmacology
- Endocrinology
Background:
- Menopausal depression is a significant mental health concern.
- γ-Oryzanol (ORY) possesses diverse biological properties.
- The effects of ORY on menopausal depression and its mechanisms remain unexplored.
Purpose of the Study:
- To investigate the antidepressant effects of γ-Oryzanol (ORY) in a mouse model of menopausal depression.
- To elucidate the underlying molecular mechanisms of ORY's action, focusing on the hippocampus and related signaling pathways.
Main Methods:
- Ovariectomized (OVX) mice were treated with ORY orally for 20 weeks.
- Behavioral tests (tail suspension, forced swim, open field) assessed depressive behavior and locomotor activity.
- Nitric oxide (NO) production, neuronal NO synthase (nNOS) expression, and signaling pathways (ERK, CREB, BDNF) were analyzed in hippocampal tissues and neurons. Molecular docking and receptor antagonist studies were also performed.
Main Results:
- ORY administration significantly reduced immobility time and increased locomotor activity in OVX mice.
- ORY upregulated hippocampal NO production and nNOS expression.
- Activation of ERK, CREB, and BDNF signaling pathways was observed, mediated through estrogen receptor beta (ERβ) and nNOS.
Conclusions:
- γ-Oryzanol (ORY) demonstrates antidepressant effects in a mouse model of menopausal depression.
- The mechanism involves ERβ-mediated upregulation of hippocampal nNOS and activation of the ERK-CREB-BDNF signaling cascade.
- ORY shows potential as a therapeutic agent for menopausal depression.
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