Low arsenic concentrations impair memory in rat offpring exposed during pregnancy and lactation: Role of α7 nicotinic receptor, glutamate and oxidative stress

Nina María Mónaco,Mariana Bartos,Sergio Dominguez,Cristina Gallegos,Cristina Bras,María Del Carmen Esandi,Cecilia Bouzat,Leda Giannuzzi,Alejandra Minetti,Fernanda Gumilar

doi:10.1016/j.neuro.2018.04.011

Abstract

Inorganic arsenic (iAs) is an important natural pollutant. Millions of individuals worldwide drink water with high levels of iAs. Arsenic exposure has been associated to cognitive deficits. However, the underlying mechanisms remain unknown. In the present work we investigated in female adult offspring the effect of the exposure to low arsenite sodium levels through drinking water during pregnancy and lactation on short- and long-term memory. We also considered a possible underlying neurotoxic mechanism. Pregnant rats were exposed during pregnancy and lactation to environmentally relevant iAs concentrations (0.05 and 0.10 mg/L). In 90-day-old female offspring, short-term memory (STM) and long-term memory (LTM) were evaluated using a step-down inhibitory avoidance task. In addition, we evaluated the α7 nicotinic receptor (α7-nAChR) expression, the transaminases and the oxidative stress levels in hippocampus. The results showed that the exposure to 0.10 mg/L iAs in this critical period produced a significant impairment in the LTM retention. This behavioral alteration might be associated with several events that occur in the hippocampus: decrease in α7-nAChR expression, an increase of glutamate levels that may produce excitotoxicity, and a decrease in the antioxidant enzyme catalase (CAT) activity.

Highlights

IntroductionArsenic causes a wide range of adverse health effects
I Inorganic Arsenic is a metalloid present in the earth’s crust
Taking into account that the deleterious health effects are associated with chronic arsenic exposure, the maximum limit of Inorganic Arsenic (iAs) in drinking water has been reduced to 0.01 mg/L by the World Health Organization and US Environmental Protection Agency (2001; WHO, 2013)

Summary

Introduction

Arsenic causes a wide range of adverse health effects. TE Chronic exposure to iAs through contaminated drinking water can damage tissue P throughout the body and it is associated to a wide range of human E diseases, such as hyperpigmentation and keratosis, different cancer types C (bladder, lung, kidney, liver, skin) and, vascular pathological conditions, such as AC Blackfoot disease, atherosclerosis, hypertension, and diabetes (Brown and Ziese, 2004; Jovanovic et al, 2012; Kapaj et al, 2006). Taking into account that the deleterious health effects are associated with chronic arsenic exposure, the maximum limit of iAs in drinking water has been reduced to 0.01 mg/L by the World Health Organization and US Environmental Protection Agency (2001; WHO, 2013)

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Results

Conclusion