Neonicotinoids are considered safe because of their low affinities to mammalian nicotinic acetylcholine receptors (nAChRs) relative to insect nAChRs. However, because of importance of nAChRs in mammalian brain development, there remains a need to establish the safety of chronic neonicotinoid exposures with regards to children’s health. Here we examined the effects of longterm (14 days) and low dose (1 μM) exposure of neuron-enriched cultures from neonatal rat cerebellum to nicotine and two neonicotinoids: acetamiprid and imidacloprid. Immunocytochemistry revealed no differences in the number or morphology of immature neurons or glial cells in any group versus untreated control cultures. However, a slight disturbance in Purkinje cell dendritic arborization was observed in the exposed cultures. Next we performed transcriptome analysis on total RNAs using microarrays, and identified significant differential expression (p < 0.05, q < 0.05, ≥1.5 fold) between control cultures versus nicotine-, acetamiprid-, or imidacloprid-exposed cultures in 34, 48, and 67 genes, respectively. Common to all exposed groups were nine genes essential for neurodevelopment, suggesting that chronic neonicotinoid exposure alters the transcriptome of the developing mammalian brain in a similar way to nicotine exposure. Our results highlight the need for further careful investigations into the effects of neonicotinoids in the developing mammalian brain.

Our research has revealed that PDGF signaling, which is known to be involved in various fibrotic diseases, also contributes to fibrotic scar formation—a barrier to nerve regeneration in the lesioned brain. This signaling plays a role in both the initiation and maintenance of fibrotic scar formation. Indeed, inhibiting PDGF signaling in vivo resulted in the disappearance of the fibrotic scar, thereby enabling nerve regeneration.

In the latter half of the 20th century, humans have produced various synthetic chemicals, several of which had serious adverse effects on ecosystems and human health. Colborn et al. noticed that some chemicals disrupt the hormonal system of living organisms. They named these chemicals endocrine-disrupting chemicals (EDCs) and published the book Our Stolen Future. In classical toxicology, toxins directly act on cellular components, such as proteins, DNA, and cell membranes; cause damage and exhibit toxicity; and demonstrate a linear dose–response relationship, thus allowing safe thresholds. EDCs transmit abnormal signals through receptors, thus causing errors in the timing, type, and quantity of gene expression, which lead to adverse effects. Through the hormonal signaling system, EDCs can exhibit hormone-disrupting effects even at low doses, thus making it difficult to establish clear thresholds. EDCs have been reported to cause adverse effects by disrupting the estrogenic, androgenic, thyroid, and other signaling systems. Therefore, EDCs affect not only the endocrine system but also the reproductive, nervous, and immune systems. Owing to the wide-ranging effects of EDCs, there is no standardized definition of EDCs, and further research is needed to scientifically clarify EDCs. However, there are accumulating reports on the health hazards to humans caused by EDCs. Considering the precautionary approach, regulations regarding EDCs need to be reevaluated at both the national and international levels. This review introduces and discusses recent research and public initiatives related to EDCs. Can “our stolen future” be regained?