1.Issue addressed by the project
"Intimate partner violence" (IPV), or simply "domestic violence," is the physical/sexual violence, stalking, or psychological harm perpetrated by a current/former partner/spouse. IPV affects all genders, but women are most frequently impacted, with 15–71% of women worldwide experiencing IPV, resulting in significant stress, adverse health, and economic effects. The EU Agency for Fundamental Rights randomly performed interviews among the 28 countries of the UNION with 42,002 women aged 18-74. In their lifetime, a staggering 51.7% reported being victims of violence in their lifetime. In Italy, nearly seven million women have suffered physical or sexual violence at the hands of their partners, and 652,000 women have been raped, with a current or former partner committing 62.7% of that rapes.
1.1 Is there a pathogenic signature common to the many organs affected by IPV?
IPV is a "total body" disease state. Indeed, besides the acute traumatic body and brain injuries, chronic exposure to IPV can lead to headaches, pelvic pain, dysmenorrhea, sexual dysfunction, irritable bowel syndrome, insomnia, depression, anxiety disorders, post-traumatic stress disorder (PTSD), and cognitive decline. Each disease mentioned above, often comorbid, is treated symptomatically rather than holistically. We believe that finding a pathogenic signature at least partially explaining IPV-triggered multi-organ damage would usher in more effective treatments for this multifocal condition.This systemic disease model should not ignore female sex hormones' central role. Indeed, estrogens are a primary vehicle of resilience for female subjects.
1.2 Is there an adequate animal model mimicking human IPV?
As highlighted, there is an urgent need to advance the study of IPV beyond subjective data such as self-reports. It is imperative to obtain scientific evidence of the neurological impact and cognitive dysfunction in women with an IPV history. A lack of an animal model that encapsulates the main features of human IPV has hindered a more well-rounded understanding of IPV pathophysiology at the brain and heart levels. By extension, such deficiency has substantially precluded the possibility of conducting preclinical (animal testing) of potential new pharmacological tools to attenuate the long-term multi-organ consequences of IPV in women. Indeed, as reported below, current treatments for IPV victims are far from optimal.
2. The development plan of the present project articulates the following o objectives:
AIM 1: Using a modified mouse model of IPV (Experimental Intimate Partner Violence, EIPV), to determine whether a) reiterated EIPV in young/adult female mice alters the estrogen-BDNF signaling, thus jeopardizing hippocampal neurogenesis and synaptic plasticity, prompting anxiety/depressive-like behavior.
AIM 2 is to determine whether the chronic infusion of Estrogen Receptor agonist in EIPV-challenged female mice prevents early signs of neurological dysfunction.
