Early life exposure to environmental pollutants and toxic chemicals has been linked to learning and behavioral alterations in children. iAs exposure is associated with different types neurological disorders such as memory and learning impairment. iAs is methylated in the brain by the arsenic III-methyltransferase in a process that requires glutathione (GSH). The xCT-antiporter cell membrane transporter participates in the influx of cystine for GSH synthesis in exchange for glutamate in a 1:1 ratio. In CD-1 mice gestationally exposed to 20 ppm of sodium arsenite in drinking water, we have previously observed up-regulation of xCT in the male mouse hippocampus which caused glutamatergic synapse alterations affecting learning and memory processes. Here, we used the same gestational iAs exposure model to investigate whether the up-regulation of xCT and down-regulation of GLT-1 transporters were associated with higher levels of extracellular glutamate and changes in the expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor, responsible for excitatory fast synaptic transmission. The induction of LTP in the perforant-dentate gyrus pathway (PP-DG) of the hippocampus was also studied, as well as learning and memory formation using the water maze test. Changes in GSH levels were also tested in the hippocampus of animals exposed to iAs. Results showed increased GSH synthesis (p < 0.05), associated with significantly higher extracellular glutamate levels in iAs exposed mice. Exposure was also significantly associated with AMPA subunits down-regulation, deficient LTP induction, and lower excitability of the PP-DG pathway. In addition, animals showed deficient learning and memory in the Morris Water Maze test.

New neurons are continuously generated and functionally integrated into the dentate gyrus (DG) network during the adult lifespan of most mammals. The hippocampus is a crucial structure for spatial learning and memory, and the addition of new neurons into the DG circuitry of rodents seems to be a key element for these processes to occur. The Morris water maze (MWM) and contextual fear conditioning (CFC) are among the most commonly used hippocampus-dependent behavioral tasks to study episodic-like learning and memory in rodents. While the functional contribution of adult hippocampal neurogenesis (AHN) through these paradigms has been widely addressed, results have generated controversial findings. In this review, we analyze and discuss possible factors in the experimental methods that could explain the inconsistent results among AHN studies; moreover, we provide specific suggestions for the design of more sensitive protocols to assess AHN-mediated learning and memory functions.