An investigation of the uptake, distribution, and accumulation of lead and other trace elements in caprine brain tissues using analytical atomic spectrometry.

摘要

Exposure to toxic elements and dysregulation of essential elements have been implicated in neurodegenerative disorders. Despite the importance of trace elements in neurological function, little is known regarding their uptake and distribution within brain tissues. Even less is known regarding the impact of toxic metal exposure (i.e., Pb) on endogenous metals within the brain.;To increase our understanding of Pb uptake and accumulation in specific brain regions, and how this may affect other trace elements, intact brains were obtained from a convenience sample of goats that were dosed with various amounts of Pb for many years to produce blood lead pools. Each brain was dissected into 14 regions of interest; additional tissues included the olfactory epithelium and spinal cord. The tissues were analyzed for Pb and eight other trace elements (Cd, Co, Cu, Mn, Mo, Zn, Ba, and Cs) by inductively coupled plasma mass spectrometry, following microwave-assisted acid digestion. Associations were explored between brain Pb, bone Pb and historical blood Pb (BPb) levels.;Lead was detected in virtually all brain regions of interest, except for one un-dosed animal that had detectable environmental levels of Pb in many, but not all regions. Among all animals, significant Pb enrichment was observed in the olfactory epithelia relative to the various brain regions. Lead was also found to accumulate in the olfactory bulbs and choroid plexus, along with other metals such as copper and cobalt. Associations between four BPb indices of exposure (recent BPb, peak BPb, average lifetime BPb, and cumulative BPb index (CBLI)) and (a) lifetime Pb dose, (b) bone Pb, and (c) brain Pb were evaluated. Peak BPb and CBLI were associated with lifetime Pb dose. Surface bone Pb levels were associated with CBLI. A non-linear relationship was observed between recent BPb and brain Pb, characterized by a steep slope that reached a plateau above 10 microg/dL BPb. Recent BPb best described brain Pb content in the dosed goats using an exponential model. These data suggest a possible saturation of brain tissues by Pb. This observation may provide a plausible biological mechanism for population-based childhood lead exposure studies, that report a steeper inverse slope of lead-associated decrements in global measures of cognitive indices at BPb levels < 10 microg/dL. Significant associations between tissue Pb levels and other metals (Mn, Zn, Ba, Cs) were observed in brain regions including the deep cerebellar nuclei, caudate nucleus, occipital, and frontal lobes. Correlations between other trace elements were observed in several brain areas that are rich in grey matter (hippocampus, parietal lobe, medulla, thalamus). A single olfactory bulb was subjected to X-Ray microanalysis at the Cornell High Energy Synchrotron Source. Imaging for Pb, Mn, Cu, and Zn was attempted, with the latter two elements providing some interesting patterns of distribution. This study provides a unique perspective on the uptake and accumulation of lead, along with other trace elements, in the brains of goats receiving long-term oral Pb dosing.