Perinatal ω-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood

doi:10.1073/pnas.0502594102

Perinatal ω-3 polyunsaturated fatty acid supply modifies brain zinc homeostasis during adulthood

^*Howard Florey Institute of Experimental Physiology and Medicine and ^†Department of Optometry and Vision Sciences, University of Melbourne, Melbourne, Victoria 3052, Australia; ^‡School of Biological and Chemical Sciences, Deakin University, Geelong, Victoria 3125, Australia; ^§Department of Food Science, RMIT University, Melbourne, Victoria 3000, Australia; ^∥School of Aquatic and Fishery Sciences, University of Washington, Seattle, WA 98195; and ^**Laboratory of Functional Genomics, Biological Research Center, Hungarian Academy of Sciences, Szeged, H-6701, Hungary

Contributed by John E. Halver, March 30, 2005

Abstract

Dietary ω-3 polyunsaturated fatty acid (PUFA) influences the expression of a number of genes in the brain. Zinc transporter (ZnT) 3 has been identified as a putative transporter of zinc into synaptic vesicles of neurons and is found in brain areas such as hippocampus and cortex. Neuronal zinc is involved in the formation of amyloid plaques, a major characteristic of Alzheimer's disease. The present study evaluated the influence of dietary ω-3 PUFA on the expression of the ZnT3 gene in the brains of adult male Sprague-Dawley rats. The rats were raised and/or maintained on a control (CON) diet that contained ω-3 PUFA or a diet deficient (DEF) in ω-3 PUFA. ZnT3 gene expression was analyzed by using real-time PCR, free zinc in brain tissue was determined by zinquin staining, and total zinc concentrations in plasma and cerebrospinal fluid were determined by atomic absorption spectrophotometry. Compared with CON-raised animals, DEF-raised animals had increased expression of ZnT3 in the brain that was associated with an increased level of free zinc in the hippocampus. In addition, compared with CON-raised animals, DEF-raised animals had decreased plasma zinc level. No difference in cerebrospinal fluid zinc level was observed. The results suggest that overexpression of ZnT3 due to a perinatal ω-3 PUFA deficiency caused abnormal zinc metabolism in the brain. Conceivably, the influence of dietary ω-3 PUFA on brain zinc metabolism could explain the observation made in population studies that the consumption of fish is associated with a reduced risk of dementia and Alzheimer's disease.

Footnotes

↵ †† To whom correspondence should be addressed. E-mail: pusi{at}brc.hu.
↵ ¶ Present address: School of Psychological Science, Faculty of Science, Technology, and Engineering, La Trobe University, Melbourne, Victoria 3086, Australia.
Author contributions: R.S.W., A.J.S., and A.P.J. designed research; A.P.J., M.L.A., M.L.M., H.S.W., R.S.W., K.K., A.J.S., and L.G.P. performed research; M.L.A. contributed new reagents/analytic tools; R.S.W., A.P.J., A.J.S., M.L.M., M.L.A., L.G.P., and J.E.H. analyzed data; and A.P.J., R.S.W., A.J.S., M.L.A., M.L.M., J.E.H., and L.G.P. wrote the paper.
Abbreviations: Aβ, amyloid β-peptide; AD, Alzheimer's disease; ALA, α-linolenic acid; CSF, cerebrospinal fluid; DHA, docosahexaenoic acid; PUFA, polyunsaturated fatty acid; ZnT, zinc transporter; APP, amyloid precursor protein; CON, control diet; DEF, deficient diet; DEF-CON, born to deficient mothers and raised from weaning on a CON diet; CON-CON, born to CON mothers and raised until adulthood on a CON diet; DEF-DEF, born to DEF mothers and raised until adulthood on a DEF diet.