Hormonal Influences on Mood Disorders in Female Models

Hormones produced by the ovaries and their downstream signalling pathways exert profound effects on affective states across the female lifespan. Fluctuations in oestradiol and progesterone modulate neurotransmitter systems, neuroimmune interactions and synaptic plasticity, thereby shaping vulnerability and resilience to mood disorders. Animal models employing ovariectomy, hormone replacement and stress paradigms have elucidated mechanisms by which oestrogen receptors influence inflammatory cytokine cascades, neurotrophic support and hypothalamic–pituitary–adrenal axis regulation. These investigations reveal that hormonal decline can precipitate neuroinflammatory responses, reduce brain-derived neurotrophic factor levels and impair dendritic architecture within limbic circuits. Conversely, targeted interventions—ranging from phytoestrogen supplementation to dietary modulation—highlight the potential to restore homeostasis, offering practical pathways to mitigate depression and anxiety in post-reproductive states.

Research from Nature Portfolio

Computational network analyses have identified oestrogen receptor-linked proteins as key mediators of antidepressant-like effects in preclinical models, implicating PI3K/AKT and MAPK signalling pathways in the action of botanical compounds. Molecular docking and dynamic simulations have confirmed high-affinity interactions between natural ligands and core targets such as AKT1, MAPK14 and ESR1, suggesting multi-target therapeutic potential. Complementary experimental work in ovariectomised rodents fed a high-fat diet demonstrates that oestrogen replacement attenuates lipid-associated metabolic dysfunction and ameliorates depressive-like behaviours, while dietary lipids modulate serotonergic and leptin signalling. Together, these findings underscore hormone-nutrient interactions in shaping mood and support a systems-level approach to antidepressant development.

Hormonal Influences on Mood Disorders in Female Models publication trend

The graph below shows the total number of articles in hormonal influences on mood disorders in female models across all publications each year (not limited to Nature Index journals).

Technical terms

Ovariectomy: The surgical removal of ovaries in animal models to mimic hormonal deficiency.

Estradiol: The primary form of oestrogen involved in reproductive and neural functions.

Estrogen receptors (ERα, ERβ, GPER): Cell-surface or nuclear receptors that mediate oestrogen signalling.

Neuroinflammation: Activation of immune responses in the central nervous system marked by cytokine release.

Neuroplasticity: The capacity of neural circuits to remodel structurally and functionally in response to stimuli.

Hypothalamic–pituitary–adrenal (HPA) axis: The neuroendocrine system governing stress responses through corticotrophin release.

Brain-derived neurotrophic factor (BDNF): A protein essential for neuronal survival, growth and synaptic plasticity.

References

1. Antidepressant-like effects of the Punica granatum and citalopram combination are associated with structural changes in dendritic spines of granule cells in the dentate gyrus of rats. Frontiers in Pharmacology (2023).
2. Bioinformatics and computational chemistry approaches to explore the mechanism of the anti-depressive effect of ligustilide. Scientific Reports (2023).
3. High-Fat Feeding Improves Anxiety-Type Behavior Induced by Ovariectomy in Rats. Frontiers in Neuroscience (2018).
4. Prevotella histicola Mitigated Estrogen Deficiency-Induced Depression via Gut Microbiota-Dependent Modulation of Inflammation in Ovariectomized Mice. Frontiers in Nutrition (2022).