Transient Maternal IL-6 Mediates Long-Lasting Changes in Neural Stem Cell Pools by Deregulating an Endogenous Self-Renewal Pathway

The mechanisms that regulate the establishment of adult stem cell pools during normal and perturbed mammalian development are still largely unknown. Here, we asked whether a maternal cytokine surge, which occurs during human maternal infections and has been implicated in cognitive disorders, might have long-lasting consequences for neural stem cell pools in adult progeny. We show that transient, maternally administered interleukin-6 (IL-6) resulted in an expanded adult forebrain neural precursor pool and perturbed olfactory neurogenesis in offspring months after fetal exposure. This increase is likely the long-term consequence of acute hyperactivation of an endogenous autocrine/paracrine IL-6-dependent self-renewal pathway that normally regulates the number of forebrain neural precursors. These studies therefore identify an IL-6-dependent neural stem cell self-renewal pathway in vivo, and support a model in which transiently increased maternal cytokines can act through this pathway in offspring to deregulate neural precursor biology from embryogenesis throughout life. •A single maternal injection of IL-6 causes an expansion of the adult NSC pool•An expanded NSC pool is a result of enhanced self-renewal of embryonic precursors•Maternal IL-6 acts on an endogenous IL-6 self-renewal pathway•Maternal cytokine flares during embryogenesis can impact brain development long term A maternal surge of the cytokine interleukin-6 (IL-6), mimicking maternal infection, activates a newly identified self-renewal pathway in offspring that expands the embryonic neural precursor pool, resulting in perturbed adult neurogenesis.