Understanding the role of microglia in ‘chemofog’ to resolve chemotherapy-induced cognitive impairment

Cancer survivors treated with chemotherapy experience persistent memory deficits, commonly known as ‘chemofog’. Currently there are no effective treatments for chemotherapy-induced cognitive impairment, and the underlying molecular mechanisms are poorly understood. Recent evidence suggests that chemotherapy induces chronic microglia reactivity, the brain’s resident immune cells, which could drive alterations in neuroplasticity mechanisms ultimately causing memory impairment. In this study we want to investigate the role of microglia in chemotherapy-induced learning and memory impairment in a rodent model of ‘chemofog’.We use a loss-of-function strategy (microglia depletion) to determine the role of these cells on the long-lasting effects of the widely used chemotherapeutic Doxorubicin (Dox) on fear memory, dendritic spines and synaptic neurotransmission (AMPA receptor mediated currents) in the basolateral amygdala (BLA). A better understanding of the cellular and molecular underpinnings of ‘chemofog’ will facilitate the development of new therapeutic strategies aimed at ameliorating these long-lasting impairments.