Chemotherapy-induced cognitive impairment and glia: A new take on chemobrain?

The significant rise in cancer survivorship stands out as one of the most notable achievements of modern science. However, this comes with a significant burden, as cancer treatment is not without adverse effects. Lately, there has been a growing focus on cognitive dysfunction associated with cancer treatment, often referred to as 'chemobrain'. It significantly impacts the quality of life for cancer survivors. The underlying mechanisms studied so far usually focus on neurons, while other cells of the central nervous system are often overlooked. This review seeks to place the hypothesis that glial cells may play a role in the development of chemotherapy-induced cognitive dysfunction. It summarizes the primary mechanisms proposed to date while underscoring the existing gaps in this research field. Inflammation and release of pro-inflammatory mediators by M1 microglia and A1 astrocytes are the most prevalent findings after chemotherapy. However, activation of A1 astrocytes by some chemotherapeutic agents may contribute to neuronal degeneration, alterations in synaptic branches, as well as glutamate excitotoxicity, which can contribute to cognitive impairment. Furthermore, the reduction in the number of oligodendrocytes after chemotherapy may also impact the myelin sheath, contributing to 'chemobrain'. Furthermore, some chemotherapeutic drugs activate M1 microglia, which is associated with decreased neuroplasticity and, possibly, cognitive impairment. In conclusion, data regarding the effects of chemotherapy on glial cells are scarce, and it is essential to understand how these cells are affected after cancer treatment to enable reliable therapeutic or preventive actions on cancer-treated patients.