Abstract
Methylmercury (MeHg) is a potent neurotoxic chemical, and gestational exposure to MeHg is known to cause developmental impairments in fetuses. Although it is well established that fetuses are extremely susceptible to MeHg toxicity, limited studies have investigated the effect of low-level MeHg exposure on mothers. In this study, we demonstrated that exposure of pregnant rats to low-level MeHg (1 ppm in drinking water) induced cerebellar synaptic and neuritic remodeling during the perinatal period between gestational day 20 and postnatal day (PND) 1. MeHg-induced neurodegeneration, for example, cerebellar granule cell death, was not detected and fetuses were delivered normally and exhibited normal development. The maternal cerebellar synaptic and neuritic changes were restored by PND 21. To elucidate the mechanisms underlying these perinatal changes in MeHg-exposed pregnant rats, we investigated proteins related to synapse formation and neurite outgrowth. We identified suppression of the tropomyosin receptor kinase (Trk) A pathway and reduced activity-regulated cytoskeleton-associated protein (Arc) expression in MeHg-exposed pregnant rats during the perinatal period, mirroring the decreased expression of synaptic and neuritic proteins. MeHg-exposed pregnant rats also exhibited increased perinatal plasma corticosterone levels and decreased estradiol levels compared to vehicle-exposed pregnant rats. Similar to the synaptic and neuritic changes, TrkA pathway activity, Arc expression, and plasma hormone levels were subsequently normalized. These results suggest that exposure of pregnant rats to low-level MeHg affected perinatal cerebellar synaptic and neuritic remodeling through modulation of the TrkA pathway and Arc expression which may be caused by MeHg-induced hormonal changes.
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We are grateful to Ayumi Onitsuka and Michiko Fuchigami for their excellent technical assistance.
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Fujimura, M., Usuki, F. Pregnant rats exposed to low-level methylmercury exhibit cerebellar synaptic and neuritic remodeling during the perinatal period. Arch Toxicol 94, 1335–1347 (2020). https://doi.org/10.1007/s00204-020-02696-4
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DOI: https://doi.org/10.1007/s00204-020-02696-4