Effect of Methamidophos on cerebellar neuronal cells

Abstract

Summary: Methamidophos is a toxic organophosphorus compound that inhibits acetlycholinesterase activity, and induces neurotoxicity. It is a synthetic chemical commonly used as pesticides to limit pest damages to cultivated plants. Currently, there is serious public health concern over its safety and use due to its global nature, persistence and bioaccumulations. We have previously reported that methamidophos suppressed thyroid hormone receptor (TR)-mediated transcription, but did not dissociate the interaction between TR and its response element (thyroid hormone  response element; TRE), neither did it interact with nuclear cofactors. In the present study, we investigated the effects of methamidophos on  cerebellar neuronal cells. Using primary cerebellar culture from new born rats, We observed that Purkinje cell dendrite arborization were greatly impaired in the absence of thyroid hormone (TH), However, low dose  methamidophos 10^-6 M did not significantly impair dendrite arborization of cerebellar Purkinje cells in the presence of thyroid hormone (TH). However, using granule cell reaggregate culture, we observed that low dose  methamidophos 10^-6 M remarkably suppressed granule cell neurite extension in the presence of TH. Taken together, our study shows that low dose methamidophos may negatively impact TH-mediated cerebellar neuronal cell development and function, and consequently could interfere with TH-regulated neuronal events.

Keywords: Methamidophos, Thyroid hormone, Purkinje cells, Granule cell, Neuronal development