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Summary Maternal immune activation (MIA) during pregnancy is a major risk factor for adverse obstetric outcomes and neurodevelopmental disorders in offspring; yet the underlying mechanisms and effective interventions are not well established. Here, we identify a pivotal role of α7nAChR (nicotinic acetylcholine receptor)-mediated activation in splenic macrophages, which triggers an interleukin-6-driven inflammatory cascade, affecting the disruption of maternal-fetal immune balance. This process contributes to miscarriage, diminished neonatal survival, and long-term neuropsychiatric deficits in adulthood. We further identified that the paraventricular nucleus-vagus-α7nAChR-spleen circuit is a central regulator for gestational neuroimmune homeostasis. Prenatal electroacupuncture stimulation (ES) modulates macrophage activation and immune equilibrium at the maternal-fetal interface by engaging these circuits, improving perinatal outcomes, and mitigating neurodevelopmental impairments in offspring. These findings position the brain-spleen axis as a promising therapeutic target and support prenatal ES as a viable non-pharmacological strategy for preventing MIA-related complications.
Zhang et al. (Sat,) studied this question.