Resumo

An important question that remains unanswered is whether the predominant cause of cognitive decline in high-grade glioma patients is the treatment or the tumor itself. Several studies finding brain tumors and the progression of these tumors to be the predominant causes of cognitive deterioration in this population. A small number of studies have demonstrated the use of animal models to verify cognitive deficits associated with tumor progression. In fact, nude mice, an animal model widely used for cancer research, has not been exploited as a tool to perform parallel analysis of tumor progression and behavior. The aim of this work was to validate a rapid and efficient method for evaluate cognitive performance and tumor progression in nude mice with orthotopic xenografts of the human glioblastoma cell line U87MG. After four days of habituation, mice were submitted to a training phase with two identical objects and the exploration time was measured. Ninety minutes or twenty four hours latter, a test phase was performed with one of the objects being replaced by a new one and the time of exploration determined. Nine, twelve and seventeen days post cell implantation into striatum (5 x 10e5 cells/animal), mice were trained for the object recognition task (RO). Healthy nude mice as well as animals 9 days post glioblastoma cells implantation were equally able to recognize new objects ninety minutes or twenty four hours after training. However, considerable impairment was noticed in the cognitive performance of mice bearing xenografts after 12 and 17 days post implantation when compared with naïve animals, suggesting that cognition deficits might be related to the growth of the glioblastoma. This work demonstrates an efficient and feasible approach to evaluate behavior deficits during tumor progression in animal models and point for a potential functional analysis of the cognition performance in preclinical trials of compounds that target tumor growth inhibition. Supported by FAPESP, CNPq and CAPES.