【文章名】Protection of Hippocampal Neurogenesis from Toll-Like Receptor 4-Dependent Innate Immune Activation by Ablation of Prostaglandin E-2 Receptor Subtype EP1 or EP2
Protection of Hippocampal Neurogenesis from Toll-Like Receptor 4-Dependent Innate Immune Activation by Ablation of Prostaglandin E-2 Receptor Subtype EP1 or EP2
[摘要]：Prostaglandin E-2 is one of several eicosanoid products of the cyclooxygenase isozymes and is a key regulator of innate immune responses; it also possesses paracrine effects on mature neurons. The prostaglandin E, receptor family consists of four subtypes of which EP1 and EP2 are known to be expressed by microglia. Lipopolysaccharide (LPS)-induced innate immune activation leads to the degeneration of intermediate progenitor cells (IPCs) that are destined for neuronal maturation in the hippocampal subgranular zone (SGZ); these cells can be identified by the expression of the transcription factor T-box brain gene 2 (Tbr2). Importantly, depletion of LPS-induced IPCs from the SGZ is suppressed by cyclooxygenase inhibitors. We therefore tested the hypothesis that either EP1 or E132 is critical to LPS-induced depletion of Tbr2+ IPCs from the SGZ. Expression of either EP1 or EP2 was necessary for Toll-like receptor 4-dependent innate immune-mediated depletion of these Tbr2+ IPCs in mice. Moreover, EP1 activation was directly toxic to murine adult hippocampal progenitor cells; EP2 was not expressed by these cells. Finally, EP1 modulated the response of murine primary microglia cultures to LPS but in a manner distinct from EP2. These results indicate that prostaglandin E-2 signaling via either EP1 or EP2 is largely to completely necessary for Toll-like receptor 4-dependent depletion of IPCs from the SGZ and suggest further pharmacological strategies to protect this important neurogenic niche. (Am J Pathol 2009,174:2300-2309; DOI: 10.2353/ajpath.2009.081153)
