ArticleNeuroscience2011
Long-term ovariectomy decreases serotonin neuron number and gene expression in free ranging macaques.
Article in Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- The Impact of Estradiol Dynamics During the Menopause Transition on Depression Risk: A Narrative Review of Estradiol's Neurobiological Mechanisms.Biological psychiatry · 2026Review
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Motor unit discharge properties are modestly influenced by menstrual cycle-related fluctuations in sex hormone concentrations.bioRxiv : the preprint server for biology · 2026Article
- Estradiol metabolism by gut microbiota in women's depression pathogenesis: inspiration from nature.Frontiers in psychiatry · 2025Review
- Associations of serotonin-related brain morphology in early adolescence with behavioral and emotional problems.NeuroImage. Clinical · 2025Article
- Article
- Sexual dimorphism in colorectal cancer: molecular mechanisms and treatment strategies.Biology of sex differences · 2024Review
- The impact of estradiol on serotonin, glutamate, and dopamine systems.Frontiers in neuroscience · 2024Review
- The intersection between menopause and depression: overview of research using animal models.Frontiers in psychiatry · 2024Review
- Estimates of persistent inward currents in lower limb motoneurons are larger in females than in males.Journal of neurophysiology · 2023Article
- Environmental Pollution to Blame for Depressive Disorder?International journal of environmental research and public health · 2022Article
- Sex-Bias in Irritable Bowel Syndrome: Linking Steroids to the Gut-Brain Axis.Frontiers in endocrinology · 2021Review
- Role of Estradiol in the Expression of Genes Involved in Serotonin Neurotransmission: Implications for Female Depression.Current neuropharmacology · 2019Review
- Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents.International journal of tryptophan research : IJTR · 2018Article
- How Studies of the Serotonin System in Macaque Models of Menopause Relate to Alzheimer's Disease1.Journal of Alzheimer's disease : JAD · 2017Review
- Ovarian steroids regulate gene expression related to DNA repair and neurodegenerative diseases in serotonin neurons of macaques.Molecular psychiatry · 2015Article
- Androgen metabolites impact CSF amines and axonal serotonin via MAO-A and -B in male macaques.Neuroscience · 2015Article
- High fat diet decreases beneficial effects of estrogen on serotonin-related gene expression in marmosets.Progress in neuro-psychopharmacology & biological psychiatry · 2015Article
- A Role for Estrogen in Schizophrenia: Clinical and Preclinical Findings.International journal of endocrinology · 2015Review
- Relationships between androgens, serotonin gene expression and innervation in male macaques.Neuroscience · 2014Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The serotonin system responds to the ovarian steroids, estradiol (E) and progesterone (P), in women and female animal models. In macaques, ovarian steroid administration to ovariectomized (Ovx) individuals improves serotonin neural function through actions on pivotal serotonin-related genes and proteins, such as TPH2 (tryptophan hydroxylase 2), SERT (serotonin reuptake transporter), and the 5HT1A autoreceptor. In addition, ovarian steroid administration reduces gene and protein expression in the caspase-independent pathway and reduces DNA fragmentation in serotonin neurons. This study examines the hypothesis that long-term ovariectomy will lead to a loss of serotonin neurons and compromised gene expression in serotonin neurons. Female Japanese macaques were ovariectomized or tubal ligated (n=5/group) at 3 years of age and returned to their natal troop. After 3 years, the animals were collected, administered a fenfluramine challenge to determine global serotonin availability, and then euthanized. Fev, TPH2, SERT, and 5HT1A expression were examined with digoxigenin in situ hybridization (ISH) and quantitative image analysis. Cell number, positive pixel area, and average pixel density were determined. In the Ovx group, Fev, TPH2, SERT, and 5HT1A showed a significant decease in average and total cell number and positive pixel area. The reduction in Fev-positive neurons suggests that there were fewer serotonin neurons in Ovx animals compared to ovary-intact animals. The decrease in TPH2 in the Ovx animals was consistent with earlier results in 5-month Ovx animals, but it may be due to the decrease in cell number rather than a decrease in expression on an individual cell basis. The decrease in SERT and 5HT1A in long-term Ovx differed from previous studies in short-term Ovx. In summary, long-term ovarian steroid loss resulted in fewer serotonin neurons and overall lower Fev, TPH2, SERT, and 5HT1A gene expression. This may be due to serotonin cell death or to a negative impact on a long-term developmental process in young female macaques.
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Registered trials
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.