TLX is an intrinsic regulator of the negative effects of IL-1β on proliferating hippocampal neural progenitor cells

Abstract

Hippocampal neurogenesis is a lifelong process whereby new neurons are produced and integrate into the host circuitry within the hippocampus. It is regulated by amultitude of extrinsic and intrinsic regulators and is believed to contribute to certain hippocampal-dependent cognitive tasks. Hippocampal neurogenesis and associated cognition have been demonstrated to be impaired after increases in the levels of proinflammatory cytokine IL-IL-1β in the hippocampus, such as that which occurs in various neurodegenerative and psychiatric disorders. IL-IL-1β also suppresses the expression of TLX (orphan nuclear receptor tailless homolog), which is an orphan nuclear receptor that functions to promote neural progenitor cell (NPC) proliferation and suppress neuronal differentiation; therefore, manipulation of TLX represents a potential strategy with which to prevent the antiproliferative effects of IL-IL-1β. In this study, we assessed the mechanism that underlies IL-IL-1β-induced changes in TLX expression and determined the protective capacity of TLX to mitigate the effects of IL-IL-1β on embryonic rat hippocampal neurosphere expansion.We demonstrate that IL-IL-1β activated the NF-κB pathway in proliferating NPCs and that this activation was responsible for IL-IL-1β-induced changes in TLX expression. In addition, we report that enhancing TLX expression prevented the IL-IL-1β-induced suppression of neurosphere expansion. Thus, we highlight TLX as a potential protective regulator of the antiproliferative effects of IL-IL-1β on hippocampal neurogenesis.-Ó'Léime, C. S., Kozareva, D. A., Hoban, A. E., Long-Smith, C. M., Cryan, J. F., Nolan, Y. M. TLX is an intrinsic regulator of the negative effects of IL-IL-1β on proliferating hippocampal neural progenitor cells.