Abstract
Nonylphenol (NP), a widely diffused persistent organic pollutant (POP), has been shown to impair cerebellar development and cause cerebellum-dependent behavioral and motor deficits. The precise proliferation of granule cell precursors (GCPs), the source of granular cells (GCs), is required for normal development of cerebellum. Thus, we established an animal model of perinatal exposure to NP, investigated the effect of NP exposure on the cerebellar GCPs proliferation, and explored the potential mechanism involved. Our results showed that perinatal exposure to NP increased cerebellar weight, area, and internal granular cell layer (IGL) thickness in offspring rats. Perinatal exposure to NP also resulted in the GCPs hyperproliferation in the external granular layer (EGL) of the developing cerebellum, which may underlie the above-mentioned cerebellar alterations. However, our results suggested that perinatal exposure to NP had no effects on the length of GCPs proliferation. Meanwhile, perinatal exposure to NP also increased the activation of Notch2 signaling, the regulator of GCPs proliferation. In conclusion, our results supported the idea that exposure to NP caused the hyperproliferation of GCPs in the developing cerebellum. Furthermore, our study also provided the evidence that the activation of Notch2 signaling may be involved in the GCPs hyperproliferation.