Altered myelination and axonal integrity in adults with childhood lead exposure: A diffusion tensor imaging study

Abstract

Childhood lead exposure is associated with adverse cognitive, neurobehavioral and motor outcomes, suggesting altered brain structure and function. The purpose of this work was to assess the long-term impact of childhood lead exposure on white matter integrity in young adults. We hypothesized that childhood lead exposure would alter adult white matter architecture via deficits in axonal integrity and myelin organization. Adults (22.9 ± 1.5 years, range 20.0 to 26.1 years) from the Cincinnati Lead Study were recruited to undergo a study employing diffusion tensor imaging (DTI). The anatomic regions of association between water diffusion characteristics in white matter and mean childhood blood lead level were determined for ninety-one participants (52 female). Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were measured on an exploratory voxel-wise basis. In adjusted analyses, mean childhood blood lead levels were associated with decreased FA throughout white matter. Regions of the corona radiata demonstrated highly significant lead-associated decreases in FA and AD and increases in MD and RD. The genu, body, and splenium of the corpus callosum demonstrated highly significant lead-associated decreases in RD, smaller and less significant decreases in MD, and small areas with increases in AD. The results of this analysis suggest multiple insults appear as distinct patterns of white matter diffusion abnormalities in the adult brain. Neurotoxic insults from the significant lead burden the participants experienced throughout childhood affect neural elements differently and may be related to the developmental stage of myelination at periods of exposure. This study indicates that childhood lead exposure is associated with a significant and persistent impact on white matter microstructure as quantified with diffusivity changes suggestive of altered myelination and axonal integrity.

Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

“…Human data have demonstrated that exposure to As (Donofrio et al, 1987), Cd (Johnson, 2000) or Pb (Brubaker et al, 2009) can negatively affect the white matter integrity. However, the mechanisms by which these metals, especially in mixture, induce myelin and axon disruptions are unknown.…”

“…Arsenic (As), cadmium (Cd), and lead (Pb) are the recognized contaminants in ground water with toxic effects on developing CNS (Jadhav et al, 2007;Rai et al, 2010). A few human studies indicate the risk of the metal-mediated demyelinating disorders (Brubaker et al, 2009;Cecil et al, 2011;Donofrio et al, 1987;Johnson, 2000). Arsenic toxicity transforms axonal functions, initiated by the segmental demyelination and followed by distal degeneration (Donofrio et al, 1987).…”

“…Arsenic toxicity transforms axonal functions, initiated by the segmental demyelination and followed by distal degeneration (Donofrio et al, 1987). Childhood Pb-exposure leads to persistent impact on the white-matter microstructure, suggestive of distorted myelination and axonal integrity (Brubaker et al, 2009;Cecil et al, 2011). Gradual accumulation of Cd indicates a contribution to the etiology of the demyelinating disease, multiple sclerosis (Johnson, 2000).…”

The fate and behavior of persistent, bioaccumulative, and toxic (PBT) chemicals: examining lead (Pb) as a PBT metal

“…Studies have shown that these defects not only alter the behavior of brain cells but also have the ability to alter the function of the brain (17). These studies have shown that the IQ performances of Pb-poisoned kids are much lower than those of Pb-free kids, lasting up to their adulthood (25). These lifelong damages have been suspected to result from permanently altered structure and function of the myelin sheaths of neurons in the nervous system.…”

“…These lifelong damages have been suspected to result from permanently altered structure and function of the myelin sheaths of neurons in the nervous system. In adults who experienced childhood Pb poisoning, their neurons have been hypothesized to have much lower signal conductance (25). These significant differences in the IQs of Pbexposed children show how minute changes caused by Pb poisoning in the central nervous system are irreversible and persist into adulthood.…”