Interleukin 1 signaling modulates pro- and anti-neurogenic effects through activation of interleukin 1 receptor type 1 on different cell types

Adult hippocampal neurogenesis (AHN) occurs the dentate gyrus (DG) and is a dynamic process which functions in learning and memory. Increased AHN improves cognition and is therapeutic for neurodegeneration. However, loss of AHN is implicated in neurodegenerative disorders, thus understanding the mechanisms that modulate AHN could lead to targeted therapeutics. The master regulator of neuroinflammation, Interleukin-1 (IL-1), is a proinflammatory cytokine that signals via interleukin 1 receptor type 1 (IL-1R1) and decreases AHN. However, blockade of IL-1 signaling suppresses AHN indicating IL-1 plays an important role in regulating AHN. Delivering IL-1 into the dentate gyrus (DG) at varying doses to adult mice revealed a dose-dependent, double-edged role of IL-1 in AHN regulation. Low doses of IL-1, particularly when expressed in astrocytes, led to increased NSC proliferation in the DG, aligning with astrocytes' known supportive role in neuronal survival and plasticity. High-dose IL-1 signaling through other cell type-specific IL-1R1 pathways impairs AHN and induces neuroinflammation. We aim to track the fate of proliferating NSCs, providing insights into how IL-1 signaling influences newly born neurons. Additionally, a novel virus designed to visualize IL-1 expression will aid in identifying specific cells stimulated by IL-1 and determining whether this stimulation enhances or suppresses AHN. This comprehensive approach may unravel the intricate mechanisms behind IL-1's dose-dependent effects on AHN. This research contributes valuable insights into potential therapeutic strategies for neurodegenerative disorders by modulating IL-1 signaling pathways.