How intimate partner violence affects the female brain-heart axis
Intimate partner violence (IPV) is an incident of physical, psychological or sexual harm to a partner. The World Health Organization estimates that around a third of women around the world have been subjected to IPV. Beyond any obvious physical impacts, it causes deeper wounds. Research suggests it affects the brain-heart axis: complex physiological connections of nerves, hormones and cytokines flowing between the brain and the heart. A deeper understanding of this impact would help to treat the consequences of IPV. In the EU-funded PINK project, undertaken with the support of the Marie Skłodowska-Curie Actions (MSCA) programme, researchers explored the effects of an IPV-like situation on the brain-heart axis in mice to discover the complex mechanics of cerebral and cardiac wounds inflicted on women. Specifically, the team investigated changes, resulting from IPV, in oestrogen levels. They also studied the signalling of a molecule, known as brain-derived neurotrophic factor (BDNF), which together regulate the brain-heart axis.
The role of oestrogen in self-protection
Through the research, the team found that mimicking reiterated physical or psychological violence in mice leads to a severe depletion of the protein abundance of oestrogen beta receptors. This is crucial for maintaining different levels of protection in women, including in the brain. “For instance, oestrogen beta receptors are key to enhancing the threshold for pain sensation in females,” explains Jacopo Agrimi, MSCA research fellow at the University of Padua and researcher on the PINK project. More specifically, the data showed that once oestrogen beta receptor signalling was down-regulated, the female mice became more ‘anxious’. “And likely this is just the tip of the iceberg in terms of behavioural changes that can be altered by mimicking intimate partner violence in mice,” says Agrimi. The team have a paper currently under review for the journal ‘iScience’, which shows that female mice with the genetic deletion of oestrogen beta receptors die prematurely during the physical/psychological violence protocol. “This just attests – one more time – to the centrality of this signalling to the well-being of these female subjects,” adds Nazareno Paolocci, associate professor in the Department of Biomedical Sciences at the University of Padua.
Uncovering complex cross-talk between oestrogen and BDNF
The PINK project also made another discovery about BDNF, a key molecule for brain functions, from neuronal survival to learning and stress response. The research revealed that BDNF is also profoundly down-regulated in female mice which are victims of reiterated physical or psychological violence. “As anticipated, BDNF is a key molecule for mood control, cognition and many other things: simply put, the everyday life and functions of neuronal cells,” notes Marco Dal Maschio, associate professor in the Department of Biomedical Sciences at the University of Padua and PINK project coordinator. The team aims to explore the complex cross-talk between oestrogens, BDNF and stress hormones in future projects.
Towards a better understanding of IPV impact on women
In the future, the researchers would like to see whether similar signatures are reproduced in the brains of women who have experienced reiterated domestic violence. The team would also like to test – in their animal model – the impact of oestrogen beta-agonists, drugs that should compensate for the loss of beneficial effects exerted by oestrogen-beta stimulation. “However, we already know that injecting a beta-receptor agonist in the brain of female subjects definitely improves their mood and ‘entrepreneurial’ activity,” says Agrimi.
Keywords
PINK, oestrogen, self-protection, complex, cross-talk, oestrogen, BDNF, understanding, intimate partner violence, impact, women
