A Hypothesis of the Interaction of the Nitrergic and Serotonergic Systems in Aggressive Behavior Induced by Exposure to Lead

Abstract

The effects caused by exposure to lead (Pb) are still considered as a relevant health risk despite public policies aimed to restricting the use of this element. The toxicity limit in the blood (10 μg/dL, established by the Center for Disease Control and Prevention) has been insufficient to prevent adverse effects and even lower values have been related to neurobehavioral dysfunctions in children. Currently, there is not a safe limit of exposure to Pb. A large body of evidence points to environmental pollutant exposure as the cause of predisposition to violent behavior, among others. Considering the evidence by our group and others, we propose that Pb exposure induces alterations in the brain vasculature, specifically in nitric oxide synthases (NOS), affecting in turn the serotonergic system and leading to heightened aggressive behavior in the exposed individuals. This review article describes the consequences of Pb exposure on the nitrergic and serotonergic systems as well as its relationship with aggressive behavior. In addition, it summarizes the available therapy to prevent damage in gestation and among infants.

Keywords: aggressive behavior; central nervous system; epigenetic; lead exposure; nitrergic and serotonergic systems.

Figure 1

Proposed hypothetical scheme that summarizes the processes caused by lead (Pb) exposure. The increase in aggressive behavior is a direct consequence of alterations in the vascular-nitrergic-serotonergic system by interaction with Pb. The processes that lead to neurochemical alterations caused by Pb coincide with the behavioral alterations found in genetically modified experimental models, such as knock-out mouse for 5-HT_1B (−/−), endothelial NOS (eNOS; −/−), and neuronal nitric oxide synthases (nNOS; −/−). 5-HT: serotonin, 5-HIAA: 5-hydroxyindoleacetic acid, MAO: monoamino oxidase, TrpH: tryptophan Hydroxylase.