Department of Biomedical Sciences, University of Padova, Padova, Italy; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Lucia Bernardele
Department of Biomedical Sciences, University of Padova, Padova, Italy
Naeem Sbaiti
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Marco Brondi
Neuroscience Institute -CNR, Padova, Italy
Donato D’Angelo
Department of Biomedical Sciences, University of Padova, Padova, Italy
Marta Canato
Department of Biomedical Sciences, University of Padova, Padova, Italy
Ivan Marchionni
Department of Biomedical Sciences, University of Padova, Padova, Italy
Christian U. Oeing
Department of Internal Medicine and Cardiology, Charité University Medicine, Berlin, Germany
Giussy Barbara
Service for Sexual and Domestic Violence, Fondazione IRCSS, Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Science and Community Health, University of Milan, Milan, Italy
Beatrice Vignoli
Department of Physics, University of Trento, 38123 Trento, Italy
Marco Canossa
Department of Cellular, Computational, and Integrative Biology, University of Trento, Trento, Italy
Nina Kaludercic
Department of Biomedical Sciences, University of Padova, Padova, Italy
Gaya Spolverato
Department of Surgical Oncological and Gastrointestinal Sciences, University of Padova, Padova, Italy
Anna Raffaello
Department of Biomedical Sciences, University of Padova, Padova, Italy
Claudia Lodovichi
Neuroscience Institute -CNR, Padova, Italy; Veneto Institute of Molecular Medicine, Padova, Italy; Padova Neuroscience Center, Padova, Italy
Marco Dal Maschio
Department of Biomedical Sciences, University of Padova, Padova, Italy; Padova Neuroscience Center, Padova, Italy; Corresponding author
Nazareno Paolocci
Department of Biomedical Sciences, University of Padova, Padova, Italy; Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Corresponding author
Summary: 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.
