Impact of Perinatal Arsenic Exposure on Amino Acid Neurotransmitters and Bioenergetics Molecules in the Hippocampus of Rats

Abstract

Developmental neurotoxicity of Arsenic (As) is a major concern worldwide. High level As exposure is associated with several chronic diseases including adverse pregnancy and birth outcomes. However, very a lack of information on its ability to impair neurodevelopment at lower exposure. To date, there are very few animal studies during the perinatal period of As exposure. Although exposure to As induces developmental neurotoxicity, there is a lack of data regarding its specific effects on amino acid neurotransmitters and bioenergetics biomolecules in the hippocampus of developing rats exposed to As during the perinatal period (GD6-PD21). In continuation of previous studies, rats were exposed to As from gestational day (GD 6) through PD 21 with targeted doses of 0, 2.0, and 4.0 mg/kg/day, respectively. HPLC-UV method was used to estimate the level of amino acid neurotransmitters (aspartate, glutamate, homocysteine, glutamine, serine, and glycine) and the level of Adenosine 5’-Triphosphate (ATP), Adenosine Diphosphate (ADP), Adenosine Monophosphate (AMP), Nicotinamide Mononucleotide (NMN), Nicotinamide Adenine Dinucleotide (NAD+), reduced Nicotinamide Adenine Dinucleotide (NADH) in the hippocampus of rats after the exposure of As. Amino acid neurotransmitter levels, a predictive biomarker of As-induced developmental neurotoxicity were found to be altered. ATP, ADP, and AMP were also significantly impaired in the hippocampus of As-exposed rats. We have observed that the hippocampus is susceptible to As toxicity, both because of the high energy depletion and the alterations in the levels of selected amino acid neurotransmitters. Taken together, our results indicate that perinatal As exposure appears to be critical and vulnerable.