ArticleMolecular psychiatry2026
Estrogen receptor beta in lateral habenula mediates antidepressant effects of estrogen in postpartum-hormone-withdrawal-induced depression.
Article in Molecular psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Cross-tissue Mendelian randomization prioritizes RAB27B as a brain-derived candidate protein for postpartum depression.European archives of psychiatry and clinical neuroscience · 2026Article
- ∆FOSB in the Nucleus Accumbens Core Is Required for Increased Anxiety, but Not Decreased Social Motivation, Following Estrogen Withdrawal in Female Mice.Genes, brain, and behavior · 2026Article
- Disrupted Estrogen Homeostasis Drives Female-Specific Depressive-Like and Anxiety-Like Behaviors via Convergent ERα Downregulation in the Ventral Hippocampus.International journal of biological sciences · 2026Article
- ΔFOSB in the nucleus accumbens core is required for increased anxiety, but not decreased social motivation, following estrogen withdrawal in female mice.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
12 authors.
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Abstract
Dramatic drop in reproductive hormone, especially estrogen level, from pregnancy to postpartum period is known to contribute to postpartum depression (PPD), but the underlying mechanism and the role of the estrogen receptors (ERs) in this process were unclear. Here, we used an estrogen-withdrawal-induced PPD model following hormone simulated pregnancy (HSP) in female Sprague-Dawley rats to induce depressive-like behaviors. After estrogen withdrawal, we observe an up-regulation of astrocyte-specific potassium channel (Kir4.1) in the brain's anti-reward center lateral habenula (LHb), along with enhanced bursting and excitability of LHb neurons. Among all 3 subtypes of ERs in the LHb, only ERβ shows an HSP-correlated expression temporal dynamics. Systemic administration of selective ERβ agonist, but not agonists of other subtypes of ERs, inhibits neuronal bursting activities and blocks up-regulation of Kir4.1 in the LHb, as well as decreases estrogen-withdrawal-induced depressive-like behavior. Importantly, intra-LHb injection of ERβ agonist is sufficient to rescue depressive-like behaviors induced by estrogen withdrawal. Conversely, local knock-down of ERβ in the LHb suppresses the antidepressant-like effect of estrogen. Our results reveal a critical role of LHb in the pathogenesis of hormone-sensitive PPD and ERβ as a critical mediator of estrogen's antidepressant effects on PPD.
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