LRP1 in Adult-Born Neural Stem Cells Modulates Neurogenesis and Hippocampal Memory

(1) Background: Adult neurogenesis within the hippocampus modulates hippocampal memory and is often dysregulated in diseases that cause memory dysfunction, notably Alzheimer's disease. We have discovered a novel modulator of hippocampal neurogenesis-low-density lipoprotein receptor-related protein 1 (LRP1). (2) Methods: Using an inducible knockout of LRP1, male and female mice were subject to loss of LRP1, specifically in adult-born neural stem cells at 3 months of age. (3) Results: After 6 months with the knockout, animals without LRP1 in adult-born neural stem cells displayed behavioral phenotypes consistent with deficits in working memory and hippocampal-mediated spatial memory. We also found that over time, increasing numbers of adult-born LRP1-knockout neurons were present, although those neurons were morphologically less complex with fewer dendrites than controls. Our data suggest that the increase in the total number of adult-born neurons 6 months after knockout is due to a subtle increase in hippocampal proliferation over time. (4) Conclusions: Altogether, our data suggest that LRP1 is an important and previously unknown regulator of hippocampal neurogenesis.