Author:

Abstract:

The increase in survival rates following advances in cancer treatments demands a better understanding of the negative consequences that these treatments inflict in the quality of life of cancer survivors, who often report discomfort in the form of cognitive impairment after chemotherapy. Despite the attention that chemotherapy-induced cognitive impairment (CICI) has received in the last decades, the extent of the damage remains largely unknown. To gain further insight, this cognitive impairment should be understood as a multifactorial phenomenon that affects various areas of behavior and biomarkers as well as their interactions. In this project I investigate different pre-clinical mouse models with the aim of mimicking the chemotherapy regime of the most common pediatric cancer - acute lymphoblastic leukaemia (ALL) - using one of the cornerstone drugs in its treatment - Methotrexate (MTX). I investigate various areas of behavior, namely, cognition, social behavior, and emotional reactivity (i.e., stress and depression), in relation to potential biomarkers, such as white matter pathology and neurogenesis. Furthermore, I propose a novel pharmacological treatment with therapeutic use that aim to prevent and/or alleviate the symptoms of chemotherapy-induced cognitive impairment. This treatment is safe to use in human subjects, which could lead to inclusion in human studies and clinical trials. This project aims to contribute to the improvement of current interventions, and likewise to the development of tools for early detection of impairments.