The effects of chemotherapy during childhood on early maternal bonding and adult social and cognitive functioning in laboratory mice
Biomedical and pharmacological progress greatly improved the survival of children diagnosed with cancer, but the long-term (neurocognitive) consequences are not well understood. The central hypothesis of this project is that the quality of attachment between parents and their offspring plays a crucial role in the impact of childhood cancer treatment. Extensive research has shown that insecure attachment often provokes various social and cognitive defects in later life. Since it is ethically inappropriate to involve human infants in invasive experimental research on attachment, the present project proposes experiments in laboratory mice to investigate parent-infant bonding and adult social and cognitive performance. Using genetic approaches, we will determine the involvement of the oxytocin system in parent-infant bonding. Notably, we will assess whether elements of parent-infant bonding affect adult performance in a number of social and cognitive tasks. Additionally, we want to identify in mice whether the chemotherapeutical agent methotrexate induces alterations in parent-infant bonding and consecutive adult social and cognitive abilities. To unravel underlying mechanisms responsible for these alterations, we will determine the transcriptional and epigenetic effects of methotrexate treatment in pups. Finally, we will investigate strategies to predict and limit the negative impact of chemotherapy and consequently hope to inspire novel therapeutic interventions in humans.