ArticleeNeuro
Effects of Estrogen Therapy on the Serotonergic System in an Animal Model of Perimenopause Induced by 4-Vinylcyclohexen Diepoxide (VCD).
Article in eNeuro. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- The Role and Mechanism of Estrogen in Perimenopausal Depression.Current neuropharmacology · 2026Review
- High glucose induces hippocampal neuron impairment through the SKP1/COX7C pathway: A potential mechanism for perimenopausal depression.Acta pharmaceutica Sinica. B · 2025Article
- Mechanism of Microbiota-Gut-Brain in Perimenopausal Depression: An Inflammatory Perspective.Expert reviews in molecular medicine · 2025Review
- Reproductive aging in biological females: mechanisms and immediate consequences.Frontiers in endocrinology · 2025Review
- Dynamics of serum exosome microRNA profile altered by chemically induced estropause and rescued by estrogen therapy in female mice.GeroScience · 2024Article
- The intersection between menopause and depression: overview of research using animal models.Frontiers in psychiatry · 2024Review
- Menopause causes metabolic and cognitive impairments in a chronic cerebral hypoperfusion model of vascular contributions to cognitive impairment and dementia.Biology of sex differences · 2023Article
- Neuroendocrine pathogenesis of perimenopausal depression.Frontiers in psychiatry · 2023Review
- The Role of Hormonal Replacement Therapy in BRCA Mutated Patients: Lights and Shadows.International journal of molecular sciences · 2023Review
- Effects of Radix Polygalae on Cognitive Decline and Depression in Estradiol Depletion Mouse Model of Menopause.Current issues in molecular biology · 2021Article
- Development of a Chemical Reproductive Aging Model in Female Rats.Bio-protocol · 2021Article
- Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause.Frontiers in behavioral neuroscience · 2021Article
- Estradiol and selective estrogen receptor agonists differentially affect brain monoamines and amino acids levels in transitional and surgical menopausal rat models.Molecular and cellular endocrinology · 2019Article
- Article
- Polysaccharides ofEvidence-based complementary and alternative medicine : eCAM · 2019Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic exposure to 4-vinylcycloxene diepoxide (VCD) in rodents accelerates the natural process of ovarian follicular atresia modelling perimenopause in women. We investigated why estrogen therapy is beneficial for symptomatic women despite normal or high estrogen levels during perimenopause. Female rats (28 d) were injected daily with VCD or oil for 15 d; 55-65 d after the first injection, pellets of 17β-estradiol or oil were inserted subcutaneously. Around 20 d after, the rats were euthanized (control rats on diestrus and estradiol-treated 21 d after pellets implants). Blood was collected for hormone measurement, the brains were removed and dorsal raphe nucleus (DRN), hippocampus (HPC), and amygdala (AMY) punched out for serotonin (5-HT), estrogen receptor β (ERβ), and progesterone receptor (PR) mRNA level measurements. Another set of rats was perfused for tryptophan hydroxylase (TPH) immunohistochemistry in the DRN. Periestropausal rats exhibited estradiol levels similar to controls and a lower progesterone level, which was restored by estradiol. The DRN of periestropausal rats exhibited lower expression of PR and ERβ mRNA and a lower number of TPH cells. Estradiol restored the ERβ mRNA levels and number of serotonergic cells in the DRN caudal subregion. The 5-HT levels were lower in the AMY and HPC in peristropausal rats, and estradiol treatment increased the 5-HT levels in the HPC and also increased ERβ expression in this area. In conclusion, estradiol may improve perimenopause symptoms by increasing progesterone and boosting serotonin pathway from the caudal DRN to the dorsal HPC potentially through an increment in ERβ expression in the DRN.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.