2. Academic Validation
  3. Reiterated male-to-female violence disrupts hippocampal estrogen receptor β expression, prompting anxiety-like behavior

Reiterated male-to-female violence disrupts hippocampal estrogen receptor β expression, prompting anxiety-like behavior

  • iScience. 2024 Jul 25;27(9):110585. doi: 10.1016/j.isci.2024.110585.
Jacopo Agrimi 1 2,  Lucia Bernardele 1,  Naeem Sbaiti 2,  Marco Brondi 3,  Donato D'Angelo 1,  Marta Canato 1,  Ivan Marchionni 1,  Christian U Oeing 4,  Giussy Barbara 5 6,  Beatrice Vignoli 7,  Marco Canossa 8,  Nina Kaludercic 1,  Gaya Spolverato 9,  Anna Raffaello 1,  Claudia Lodovichi 3 10 11,  Marco Dal Maschio 1 11,  Nazareno Paolocci 1 2
Affiliations

Affiliations

  • 1 Department of Biomedical Sciences, University of Padova, Padova, Italy.
  • 2 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • 3 Neuroscience Institute -CNR, Padova, Italy.
  • 4 Department of Internal Medicine and Cardiology, Charité University Medicine, Berlin, Germany.
  • 5 Service for Sexual and Domestic Violence, Fondazione IRCSS, Ospedale Maggiore Policlinico, Milan, Italy.
  • 6 Department of Clinical Science and Community Health, University of Milan, Milan, Italy.
  • 7 Department of Physics, University of Trento, 38123 Trento, Italy.
  • 8 Department of Cellular, Computational, and Integrative Biology, University of Trento, Trento, Italy.
  • 9 Department of Surgical Oncological and Gastrointestinal Sciences, University of Padova, Padova, Italy.
  • 10 Veneto Institute of Molecular Medicine, Padova, Italy.
  • 11 Padova Neuroscience Center, Padova, Italy.
PMID: 39228787 DOI: 10.1016/j.isci.2024.110585
Abstract

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.

Keywords

Behavioral neuroscience; Molecular neuroscience; Neuroscience.

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