| Proton Magnetic Resonance Spectroscopic Evidence of Glial Effects of Cumulative Lead Exposure in the Adult Human Hippocampus Marc G. Weisskopf,1 Howard Hu,1,2 David Sparrow,2,3,4 Robert E. Lenkinski,5 and Robert O. Wright1,2 1Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA; 2The Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, USA; 3VA Boston Healthcare System, Boston, Massachusetts, USA; 4Boston University School of Medicine, Boston, Massachusetts, USA; 5Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA Abstract
Background: Exposure to lead is known to have adverse effects on cognition in several different populations. Little is known about the underlying structural and functional correlates of such exposure in humans. Objectives: We assessed the association between cumulative exposure to lead and levels of different brain metabolite ratios in vivo using magnetic resonance spectroscopy (MRS) . Methods: We performed MRS on 15 men selected from the lowest quintile of patella bone lead within the Department of Veterans Affairs' Normative Aging Study (NAS) and 16 from the highest to assess in the hippocampal levels of the metabolites N-acetylaspartate, myoinositol, and choline, each expressed as a ratio with creatine. Bone lead concentrations—indicators of cumulative lead exposure—were previously measured using K-X-ray fluorescence spectroscopy. MRS was performed on the men from 2002 to 2004. Results: A 20-µg/g bone and 15-µg/g bone higher patella and tibia bone lead concentration—the respective interquartile ranges within the whole NAS—were associated with a 0.04 [95% confidence interval (CI) , 0.00–0.08 ; p = 0.04] and 0.04 (95% CI, 0.00–0.08 ; p = 0.07) higher myoinositol-to-creatine ratio in the hippocampus. After accounting for patella bone lead declines over time, analyses adjusted for age showed that the effect of a 20-µg/g bone higher patella bone lead level doubled (0.09 ; 95% CI, 0.01–0.17 ; p = 0.03) . Conclusions: Cumulative lead exposure is associated with an increase in the myinositol-to-creatine ratio. These data suggest that, as assessed with MRS, glial effects may be more sensitive than neuronal effects as an indicator of cumulative exposure to lead in adults. Key words: bone lead, choline, glia, hippocampus, myoinositol, N-acetylaspartate, neuronal viability, proton MRS. Environ Health Perspect 115:519–523 (2007) . doi:10.1289/ehp.9645 available via http://dx.doi.org/ [Online 3 January 2007]
Address correspondence to M.G. Weisskopf, Harvard School of Public Health, Occupational Health Program, Landmark Center, 401 Park Dr., PO Box 15697, Boston MA 02215 USA. Telephone: (617) 384-8872. Fax: (617) 384-8994. E-mail: mweissko@hsph.harvard.edu This research was supported by grants from the National Institutes of Health (NIH) (R01 ES005257) , the National Center for Research Resources, General Clinical Research Center (M01RR02635) , Small Business Innovation Research (2R44 ES03918-02, K23-ES000381) , National Institute of Environmental Sciences (NIEHS) Center (ES00002) . M.G.W was supported by NIEHS grant K01-ES012653. Additional data from the VA Normative Aging Study were collected with support from the Research Services and the Cooperative Studies Program/Epidemiology Research and Information Center of the U.S. Department of Veterans Affairs, the Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC) , the NIH (grants R01-AA08941, R01-AG13006, R01-AG14345, R01-AG18436) , and the U.S. Department of Agriculture, Agricultural Research Service (contract 53-K06-510) . The views expressed in this article are those of the authors and do not necessarily represent the views of the U.S. Department of Veterans Affairs. The authors declare they have no competing financial interests. Received 23 August 2006 ; accepted 3 January 2007.
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