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Nutritional Neurosciences

Lead Exposure and (n-3) Fatty Acid Deficiency during Rat Neonatal Development Affect Subsequent Spatial Task Performance and Olfactory Discrimination¹

Sun-Young Lim, John D. Doherty^*, Kathleen McBride, Nancy J. Miller-Ihli^**, Gilberto N. Carmona, Ken D. Stark and Norman Salem, Jr^,2

Division of Ocean Science, Korea Maritime University, Busan, Korea; ^* The United States Environmental Protection Agency, Office of Pesticide Programs, Health Effects Division, Washington, DC; Laboratory of Membrane Biochemistry and Biophysics, Division of Intramural Clinical and Biological Research, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD; and ^** The Food Composition Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Beltsville, MD

²To whom correspondence should be addressed. E-mail: nsalem{at}niaaa.nih.gov.

Docosahexaenoic acid [22:6(n-3), DHA] is important for optimal infant central nervous system development, and lead (Pb) exposure during development can produce neurological deficits. Long-Evans strain rats were fed either an (n-3) deficient [(n-3) Def] diet to produce brain DHA deficiency, or an adequate [(n-3) Adq] diet through 2 generations. At the birth of the 2nd generation, the dams were subdivided into 4 groups and supplied drinking water containing either 5.27 mmol/L (Pb) or sodium (Na) acetate until weaning. Rats were killed at 3 wk (weaning) and 11 wk (maturity) for brain Pb and fatty acid analysis. Spatial task and olfactory-cued behavioral assessments were initiated at 9 wk. Rats in the (n-3) Def group had a 79% lower concentration of brain DHA compared with the (n-3) Adq group with no effect of Pb exposure. At weaning, Pb concentrations were 7.17 ± 0.47 nmol Pb/g of brain (wet weight) in the (n-3) Adq-Pb group and 6.49 ± 0.63 nmol Pb/g of brain (wet weight) in the (n-3) Def-Pb group. At maturity, the brains contained 1.30 ± 0.22 and 1.07 ± 0.12 nmol Pb/g (wet weight), respectively. In behavioral testing, significant effects of both Pb and DHA deficiency were observed in the Morris water maze probe trial and in 2-odor olfactory discrimination acquisition and olfactory-based reversal learning tasks. Both lactational Pb exposure and (n-3) fatty acid deficiency led to behavioral deficits with additive effects observed only in the acquisition of 2-odor discriminations.

KEY WORDS: • (n-3) fatty acid deficiency • neonatal development • spatial learning • olfactory discriminations • lead toxicity • Pb

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