Neurobehavioral and neurochemical effects in rats offspring co-exposed to arsenic and fluoride during development.

Arsenic (iAs) and fluoride (F) are ubiquitous in the environment. All over the world, in many countries, thousands of people are suffering from the toxic effects of arsenicals ad fluorides. These two elements are recognized worldwide as the most serious inorganic contaminants in drinking water. When two different types of toxicants are simultaneously going inside the human body they may function independently or can act as synergistic or antagonistic to one another. Although there have been reports in literature of individual toxicity of iAs and F, however, not much is known about the effects following the combined exposure to the toxicants above mentioned. In this work, we investigated the effect of the co-exposure to low levels of iAs/F through drinking water during pregnancy and lactation on central nervous system functionality in the exposed rats offspring. Wistar rats were exposed to one of these solutions: 0.05 mg/L iAs and 5 mg/L F (Concentration A) or 0.10 mg/L iAs and 10 mg/L F (Concentration B) from gestational day 0 up to post-gestational day 21. Sensory-motor reflexes a Functional Observational Battery and the locomotor activity in an open field were assessed in offspring. Additionally, the transaminases, acethylcholinesterase and catalase levels in the striatum were determined to elucidate the possible molecular mechanisms involved in locomotor and neurobehavioral disorders. The results showed that iAs/F exposition during development produces a delay reach the maturity of sensorimotor reflexes. A decrease in the nociceptive reflex response, and increase in the locomotor activity in adult rats offspring were observed. The increase in oxidative stress, the inhibition of transaminases enzymes and the inhibition of AChE in the striatum may partially regulate all the neurobehavioral disorders observed.

Prenatal Exposure to Cadmium During Organogenesis Impairs Memory in Young Rats.

Pregnant rats were treated with 0.3 and 0.6 mg cadmium (CdCl2)/kg injected subcutaneously on a daily basis from gestational day 7 to day 15 (organogenesis period). One control group was not injected and other received saline. The 45-day-old offspring were tested in a step-down inhibitory avoidance to evaluate short-term and long-term memory and in a radial maze for the study of spatial memory. These studies showed that gestational exposure to 0.6 mg Cd/kg produced in the male offspring a significant impairment in the retention of long-term memory evaluated 24 hours after training in the step-down inhibitory avoidance. The radial maze also demonstrated that the male offspring prenatally exposed to 0.6 mg Cd presented a significant deficit in the retention of spatial memory evaluated 42 days after training. These results demonstrate that the exposure to Cd during organogenesis may affect the retention of some types of memory.

Alterations in the memory of rat offspring exposed to low levels of fluoride during gestation and lactation: Involvement of the α7 nicotinic receptor and oxidative stress.

Daily exposure to fluoride (F) depends mainly on the intake of this element with drinking water. When administered during gestation and lactation, F has been associated with cognitive deficits in the offspring. However, the mechanisms underlying the neurotoxicity of F remain obscure. In the current study, we investigated the effects of oral exposure to low levels of F during the gestational and lactation periods, on the memory of adult female rat offspring. We also considered a possible underlying neurotoxic mechanism. Our results showed that this exposure reduced step-down latency in the inhibitory avoidance task, and decreased both mRNA expression of the α7 nicotinic receptor (nAChR) and catalase activity in hippocampus. Our data indicates that low F concentrations administrated during gestation and lactation decrease the memory of 90-day-old female offspring. This suggests that the mechanism might be connected with an α7 nAChR deficit in the hippocampus, induced by oxidative stress.

Perinatal Glyphosate-Based Herbicide Exposure in Rats Alters Brain Antioxidant Status, Glutamate and Acetylcholine Metabolism and Affects Recognition Memory.

Glyphosate-based herbicides (Gly-BHs) lead the world pesticide market. Although are frequently promoted as safe and of low toxicity, several investigations question its innocuousness. Previously, we described that oral exposure of rats to a Gly-BH during pregnancy and lactation decreased locomotor activity and anxiety in the offspring. The aim of the present study was to evaluate the mechanisms of neurotoxicity of this herbicide. Pregnant Wistar rats were supplied orally with 0.2 and 0.4% of Gly-BH (corresponding to 0.65 and 1.30 g/l of pure Gly, respectively) from gestational day (GD) 0, until weaning (postnatal day, PND, 21). Oxidative stress markers were determined in whole brain homogenates of PND90 offspring. The activity of acetylcholinesterase (AChE), transaminases, and alkaline phosphatase (AP) were assessed in prefrontal cortex (PFC), striatum, and hippocampus. Recognition memory was evaluated by the novel object recognition test. Brain antioxidant status was altered in Gly-BH-exposed rats. Moreover, AChE and transaminases activities were decreased and AP activity was increased in PFC, striatum and hippocampus by Gly-BH treatment. In addition, the recognition memory after 24 h was impaired in adult offspring perinatally exposed to Gly-BH. The present study reveals that exposure to a Gly-BH during early stages of rat development affects brain oxidative stress markers as well as the activity of enzymes involved in the glutamatergic and cholinergic systems. These alterations could contribute to the neurobehavioral variations reported previously by us, and to the impairment in recognition memory described in the present work.

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

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.