Correlation of adult neurogenesis and cognitive performance in touchscreen tasks – assessing the novel small molecule OXS-N1 in mice

Adult hippocampal neurogenesis in the dentate gyrus is well-defined in rodents, and its role in cognitive functions as well as its potential as a therapeutic target for neurodegenerative diseases such as Alzheimer's disease remain a topic of great scientific interest. In this study, we evaluated the effects of a novel small molecule, OXS-N1, on neurogenesis and behavior in C57Bl/6 wild-type and 5xFAD Alzheimer's disease model mice, which were tested independently at different ages. Modern, home-cage based set-ups were implemented for automated, voluntary animal behavioral testing. OXS-N1 failed to enhance hippocampal cognitive functions in either cohort as assessed by two hippocampus-dependent touchscreen tasks. Contrary to previous short-term assessments, OXS-N1 also had no significant treatment effect on adult hippocampal neurogenesis in both wild-type and 5xFAD mice. We further analyzed correlations between individual mouse neurogenesis levels and behavioral performance independent of treatment. The density of adult-born neurons in the dentate gyrus showed no significant correlation with spatial pattern separation or reversal learning ability in the Location Discrimination task and did not affect associative memory acquisition in the Paired-Associates Learning task in either wild-type or 5xFAD mice. Our results provide further critical evidence on the complex role of adult neurogenesis for hippocampal cognition in health and disease.