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Introduction
Pyrethroids are a class of synthetic derivatives of pyrethrins, which are insecticidal compounds contained in pyrethrum plants (Chrysanthemum cinerariifolium). The main molecular targets of pyrethroids are voltage-gated sodium channels (VGSCs). Pyrethroids prolong the opening of these channels, resulting in a sodium tail current in both vertebrates and invertebrates (Vijverberg et al., 1982; Narahashi, 1985). Insect sodium channels are believed to be much more sensitive to pyrethroids than mammalian channels (Warmke et al., 1997). Because of their high insecticidal activity, low toxicity to mammals, and rapid metabolism (Miyamoto et al., 1995; Ray and Forshaw, 2000), pyrethroid insecticides are widely used.
Pyrethroids have been associated with some toxicity because they target the nervous systems of both mammals and insects. The most common symptom of acute poisoning by type I pyrethroids, which are devoid of an α-cyano moiety, is tremor syndrome (T-syndrome), and that by type II pyrethroids, which have an α-cyano moiety, is choreoathetosis with salivation syndrome (CS-syndrome) (Verschoyle and Barnes, 1972; Barnes and Verschoyle, 1974; Verschoyle and Aldridge, 1980). Recent epidemiological studies have shown a link between environmental and occupational exposure to pyrethroids and abnormalities such as changes in sperm quality and reproductive hormones (Saillenfait et al., 2015). Furthermore, prenatal exposure to pyrethroids appears to be a risk factor for neurodevelopmental delay and autism spectrum disorders (Shelton et al., 2014). Therefore, it is important to elucidate the effects of pyrethroids on the nervous system.
We previously demonstrated that deltamethrin (DM), a type II pyrethroid, triggers a prolonged increase in intracellular calcium concentrations and strongly elevates brain-derived neurotrophic factor (Bdnf) expression in primary cultures of rat cortical neurons (Ihara et al., 2012). Furthermore, DM has an antidepressant-like effect in mice (Takasaki et al., 2013). Although DM has a neurotrophic effect and increases neurite outgrowth in cultured neurons (Ihara et al., 2012), it remains unclear how DM affects neurite outgrowth. In the present study, we found that DM increases neurite outgrowth in cultured rat cortical neurons through tropomyosin receptor kinase B (TrkB)-mediated signaling pathways via endogenous BDNF, probably without de novo Bdnf transcription. Our present study would provide insight into one of the underlying molecular and cellular mechanisms that DM may be a risk...