Behavioral, biochemical, and molecular mechanisms of lead (lead ions)-mediated long-term memory impairment in the adult rat brain

Lead (Pb+2) is a metal ion, which is widely distributed in environment due to natural sources, but mainly due to anthropogenic releases. There is large amount of literature related to the toxicological effects of Pb+2 after acute exposure. However, less is known about the effects of low-level chronic exposure to Pb+2. The central nervous system is the most sensitive to the toxicological action of Pb +2 resulting in cognitive and behavioral dysfunctions in the mature and immature brain of humans and other vertebrates. Nevertheless, most of the behavioral studies have addressed the Pb+2 effects in young animals. Importantly, none of these studies was aimed to determine the effects of Pb+2 during memory consolidation processes. Moreover, the molecular mechanisms of Pb+2-induced neurotoxic effect in the brain are not well understood. A number of reports suggest that at least part of the effects of Pb+2 are due to its interference with normal calcium (Ca+2) signaling in neurons. Ca+2 is a second messenger playing an important role in learning and memory processes in the brain. Thus, this study was aimed to characterize the effects of Pb +2 at the behavioral, biochemical, and molecular level in the brain of adult rats. The results reported here demonstrate that intrahippocampal microinfusions of Pb+2 interferes with long-term memory (LTM) processes in the adult rat brain, while short-term memory is mostly unaffected in a hippocampal-dependent task by interfering with learning-induced changes in Ca+2 and phospholipid dependent protein kinase C (PKC). Moreover, in the last part of this work we generate hippocampal gene expression profiles for rats exposed to Pb+2 using the DNA microarray technique. Our main goal was to define delayed changes in gene expression associated to learning processes blocked by Pb+2 during acquisition. Gene expression analysis defined three main groups of genes: LTM genes (blocked by Pb+2 treatment during acquisition training); learning-related genes (those related to re-learning of some aspects of the task in Pb+2 exposed rats) and toxicity related genes (associated to cellular toxicity).