Prenatal Acetamiprid Exposure Enhances Microglial Activation in Primary Microglia Culture.

Abstract

Prenatal exposure to environmental chemicals, including pesticides, has been epidemiologically linked to neurodevelopmental disorders. Acetamiprid, a nicotine-mimetic insecticide, has been shown to cause neurotoxicity and abnormal neuronal distribution in rats. Furthermore, acetamiprid has been reported to activate microglia, the resident immune cells of the central nervous system, via a transition to an amoeboid shape with increased phagocytic activity in prenatally exposed neonatal mice. However, the impact of prenatal exposure to acetamiprid on offspring's microglial morphology and function remains inadequately understood. Here, we investigated the effects of prenatal exposure to acetamiprid on offspring microglial morphology and phagocytic function in response to ATP, which is released from distressed cells and results in microglial activation. We found that acetamiprid-exposed microglia significantly increased interleukin-1β (IL-1β) levels in both conditions, without and with ATP stimulation compared to microglia derived from offspring that were prenatally exposed to dimethyl sulfoxide or non-treated. In addition, microglia from offspring prenatally exposed to acetamiprid underwent morphological changes upon ATP stimulation. Given that elevated IL-1β levels are often accompanied by changes in phagocytic function, we next assessed phagocytosis under the same conditions. While phagocytosis was enhanced in the offspring prenatally exposed to acetamiprid, ATP failed to further induce phagocytic function. These findings suggest that prenatal exposure to acetamiprid enhances microglial activity but impairs the phagocytotic reactivity of offspring microglia to ATP stimulation. Further studies are needed to clarify the underlying mechanisms and potential neurodevelopmental consequences in humans.