Javier Del Pino received his PharmD degree at the University Complutense University of Madrid in 2004. He has two Masters in Sciences 2009 and 2010. He specialized in Neuro Toxicology and neuro developmental toxicology and received his PhD in Toxicology in 2009. In 2010 he worked in Institute of Health Carlos III in the National Center of Environmental Health. From 2010 to 2012 he was Associate Researcher at University of Massachusetts (UMASS) working in Sandra Petersen´s Lab in a National Institute of Health (NIH) project on developmental effects of TCDD endocrine disruptor on sexual differentiation. In 2016 he got a position as Associate Professor of Toxicology at the Complutense University of Madrid.
Amitraz is a formamidine insecticide/acaricide that alters different neurotransmitters levels, among other neurotoxic effects. Oral amitraz exposure (20, 50 and 80 mg/kg bw, 5 days) has been reported to increase dopamine (DA) content and to decrease its metabolites and turnover rates in the male rat brain, particularly in the striatum, prefrontal cortex, and hippocampus. However, the mechanisms by which these alterations are produced are not completely understood. Amitraz alters estradiol concentrations in the brain that regulate the enzymes responsible for this neurotransmitter synthesis and metabolism. Thus, alterations in estradiol levels in the brain could mediate the observed effects. To test these hypothesis regarding possible mechanisms, we treated male rats with 20, 50 and 80 mg/kg bw for 5 days with or without tamoxifen (TMX, 1 mg/kg bw), a selective estrogen receptor antagonist, and then isolated tissue from striatum, prefrontal cortex, and hippocampus. We then measured tissue levels of DA neurotransmitter. Amitraz produced a dose-dependent increase of the DA levels in all brain regions studied compared to the control group. The increase in DA ranged from highest to lowest in prefrontal cortex, striatum, and hippocampus. Moreover, amitraz induced a dose-dependent decrease of DOPAC and HVA metabolites content and turnover rate (DOPAC+HVA/DA) in all brain regions studied compared to the control group. There were no differences between the decrease in the DOPAC and HVA content in the hippocampus, but the decrease in the DOPAC content was higher than the decrease in the HVA content in the striatum, and the decrease in the HVA content was higher than the decrease in the DOPAC content in prefrontal cortex. The decrease of DA turnover rate (DOPAC+HVA/DA) ranged from highest to lowest in prefrontal cortex, hippocampus and striatum. TMX co-treatment with amitraz partially reversed the change in DA neurotransmitter and its metabolites levels as well as the turnover rates induced by amitraz alone in all brain regions studied. Our present results provide new understanding of the mechanisms contributing to the harmful effects of amitraz.
Paula Moyano received his JD degree at the University Complutense University of Madrid in 2013. She has a Masters in Pedagogical Sciences 2017. She specialized in neurotoxicology and legal sciences and received his PhD in Toxicology and legal medicine in 2016
Paraquat (PQ) is a widely used non-selective contact herbicide shown to produce memory and learning deficits after acute and repeated exposure similar to those induced in Alzheimer’s disease (AD). However, the complete mechanisms through which it induces these effects are unknown. On the other hand, glutamatergic system, mainly in the hippocampus, are involved on learning, memory and cell viability regulation. An alteration of hippocampal glutamatergic transmission or neuronal cell loss may induce these effects. In this regard, it has been suggested that PQ may induce cell death and affect glutamatergic transmission, which alteration could produce neuronal loss. According to these data, we hypothesized that PQ could induce hippocampal neuronal loss through glutamatergic transmission alteration. To prove this hypothesis, we evaluated in hippocampal primary cell culture, the PQ toxic effects after 24 h and 14 consecutive days exposure on neuronal viability and the glutamatergic mechanism related to it. This study shows that PQ disrupted glutamate levels through induction of glutaminase activity. In addition, PQ induced, after 24 h and 14 days exposure, cell death on hippocampal neurons that was partially mediated by glutamatergic transmission disruption. Our present results provide new view of the mechanisms contributing to PQ neurotoxicity and may explain cognitive dysfunctions observed after PQ exposure.