The American journal of pathologyApr 25, 2009

Stopping prostaglandin E2 receptors EP1 or EP2 may protect new brain cell growth in the memory system from immune response triggered by toll-like receptor 4

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Updated Apr 5, 2026

Abstract

Expression of either EP1 or EP2 is necessary for the depletion of Tbr2+ intermediate progenitor cells in the hippocampus induced by lipopolysaccharide.

Prostaglandin E2 is a key regulator of immune responses and affects mature neurons.
Lipopolysaccharide-induced immune activation leads to the loss of intermediate progenitor cells destined for neuronal maturation.
Depletion of these progenitor cells is suppressed by cyclooxygenase inhibitors.
EP1 activation was found to be directly toxic to murine adult hippocampal progenitor cells, while EP2 was not expressed by these cells.
EP1 and EP2 modulate microglial responses to lipopolysaccharide in different ways.

Simplified

Prostaglandin E2 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 E2 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 EP2 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 E2 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.

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Stopping prostaglandin E2 receptors EP1 or EP2 may protect new brain cell growth in the memory system from immune response triggered by toll-like receptor 4

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