Effects of early lead exposure on neurotransmitter systems in the brain. A review with commentary

Abstract

The mechanism by which early lead exposure alters the functional development of the brain remains an open question. One primary avenue of approach has been to study the effects of neonatal lead exposure on neurotransmitter systems. This paper reviews the published data related to the interaction of lead with each of those systems. Further, each dosing paradigm has been evaluated with a view to experimental error and interactive variables. It was concluded that factors such as the time at which pregnant animals were shipped and mode of dosing may have been uncontrolled variables causing variability in reported results between and within laboratories. The majority of publications deal with the interaction of lead with catecholamine systems and with dopamine in particular. Reports of effects are highly variable and many observations lack confirmation by other laboratories or have not been replicated. However, the bulk of observations leads to the tentative conclusion that lead does result in an altered functional state of the catecholamine systems. This is true for cholinergic function as well. Some perturbation of acetylcholine metabolism probably exists but the specificity and significance of the effect are suspect. Reports that lead alters the functional state of GABA pathways are interesting but require confirmation. The generality and variability of effects on neurotransmitter systems questions the degree of specificity that may be expected. It is suggested that lead may effect a variable change in the functional state of all these systems by limiting glucose metabolism during periods of vulnerability.