The steroid sulfatase inhibitor STX64 improves mice cognitive deficiencies associated with aging

Aging produces in brain a progressive oxidative process and neuroinflammation that deteriorates cognition. These brain dysfunctions provoke high economic and social costs to developed societies. For this reason, the search for treatments to prevent cognitive deficits associated with aging is a priority. Previous results suggest that STX64, a steroid sulfatase (STS) inhibitor, improves cognition in neurodegenerative diseases. In this work, we have designed cellular (immunohistochemistry), molecular (qPCRs with primers of inflammatory markers and cellular populations) and behaviour (mainly, object recognition and passive avoidance for the study of learning and memory) assays to know if subchronic (6 months) oral treatment with STX64 rescues cognitive dysfunction present in aging mice. The mouse strain used in our studies was C57. Our behavioural results showed that STX64 treatment improved cognition in aging mice, reflected as an improvement in object recognition and in passive avoidance tests. At cellular level, aging mice treated with STX64 showed an increase in microglial response and in hippocampal adult neurogenesis. Preliminary studies showed the C57 model of Alzheimer's Disease APP/PS1 also induced cholinergic activity in neurons after 1 month of oral treatment with STX64. The qPCR assays indicated that hippocampus from aging mice treated with STX64 express lower levels of inflammatory factors mRNA compared with untreated aging mice, though new studies are in progress to distinguish the microglial phenotypes of these animals using phenotype-specific primers. Our results indicates that STX64 may be a drug with potential therapeutic interest for the treatment of cognitive decline associated to aging and/or neurological diseases.