Reiterated male-to-female violence disrupts hippocampal estrogen receptor β expression, prompting anxiety-like behavior
Jacopo Agrimi, Lucia Bernardele, Naeem Sbaiti, Marco Brondi, Donato D’Angelo, Marta Canato et al. · 2024 · 7 citationsRead the paper
Intimate partner violence (IPV) is a significant public health concern whose neurological/behavioral sequelae remain to be mechanistically explained. Using a mouse model recapitulating an IPV scenario, we evaluated the female brain neuroendocrine alterations produced by a reiterated male-to-female violent interaction (RMFVI). RMFVI prompted anxiety-like behavior in female mice whose hippocampus displayed a marked neuronal loss and hampered neurogenesis, namely reduced BrdU-DCX-positive nuclei and diminished dendritic arborization in the dentate gyrus (DG): effects paralleled by a substantial downregulation of the estrogen receptor β (ERβ). After RMFVI, the DG harbored reduced brain-derived neurotrophic factor (BDNF) pools and tyrosine kinase receptor B (TrkB) phosphorylation. Accordingly, ERβ knockout (KO) mice had heightened anxiety and curtailed BDNF levels at baseline while dying prematurely during the RMFVI procedure. Strikingly, injecting an ERβ antagonist or agonist into the wild-type (WT) female hippocampus enhanced or reduced anxiety, respectively. Thus, reiterated male-to-female violence jeopardizes hippocampal homeostasis, perturbing the ERβ/BDNF axis and ultimately instigating anxiety and chronic stress.
What the full text shows
Shown in the lab- Reiterated male-to-female violent interaction (RMFVI) increases anxiety-like behavior in female mice. — Time in light compartment decreased from 120s ± 28s to 45s ± 27s; EPM open arm time dropped by ~95%. (Female C57BL/6 mice subjected to 21 days of RMFVI)
- RMFVI causes significant downregulation of estrogen receptor β (ERβ) in the hippocampal dentate gyrus (DG). — 70% decline in ERβ expression. (Female C57BL/6 mice after 21 days of RMFVI)
- RMFVI depletes BDNF pools and reduces TrkB phosphorylation in the hippocampal DG. — 70% reduction in BDNF expression in the DG. (Female C57BL/6 mice after 21 days of RMFVI)
- RMFVI triggers hippocampal apoptosis and impairs neurogenesis. — Cell death in the DG doubled; reduced BrdU-DCX-positive nuclei and reduced dendritic arborization. (Female C57BL/6 mice after 21 days of RMFVI)
- ERβ deficiency increases vulnerability to RMFVI. — 4 out of 9 ERβ KO mice died prematurely during the protocol. (Female ERβ KO mice vs WT mice)
- Pharmacological manipulation of hippocampal ERβ modulates anxiety. — ERβ antagonist increased anxiety (reduced light box time, p=0.013); ERβ agonist reduced anxiety (increased light box time, p=0.045). (Wild-type female mice via stereotaxic injection into the hippocampus)
- Setup
- Female C57BL/6 and CD1 mice, including ERβ knockout (KO) strains; 21-day RMFVI protocol.
- How
- The researchers used a modified resident-intruder paradigm where female mice were exposed to 21 days of physical attacks and sensory intimidation by aggressive male mice. They employed behavioral tests (LDB, EPM), immunofluorescence, TUNEL assays, and stereotaxic injections of ERβ agonists/antagonists to evaluate the ERβ/BDNF axis.
- Limitations
- Did not evaluate other brain regions (frontal cortices, insula, amygdala, hypothalamus). · Did not test daily administration of ERβ or TrkB agonists to mitigate chronic stress. · Did not evaluate glucocorticoid receptor (GR) activity in RMFVI mice.
Summarized by Gemma 4 from the open-access full text · 8 Oct 2026. Read it