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ToxSci Advance Access originally published online on October 10, 2006
Toxicological Sciences 2007 95(1):188-195; doi:10.1093/toxsci/kfl130
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Brain Manganese Accumulation is Inversely Related to {gamma}-Amino Butyric Acid Uptake in Male and Female Rats

Joel G. Anderson, Paula T. Cooney and Keith M. Erikson1

Department of Nutrition, The University of North Carolina at Greensboro, Greensboro, North Carolina 27402

1To whom corresponding should be addressed at Department of Nutrition, The University of North Carolina at Greensboro, 318 Stone Building, UNCG, PO Box 26170, Greensboro, NC 27402-6170. Fax: (336) 334-4129. E-mail: kmerikso{at}uncg.edu.

Received August 21, 2006; accepted October 6, 2006


  Abstract

Iron (Fe) is an essential trace metal involved in numerous cellular processes. Iron deficiency (ID) is reported as the most prevalent nutritional problem worldwide. Increasing evidence suggests that ID is associated with altered neurotransmitter metabolism and a risk factor for manganese (Mn) neurotoxicity. Though recent studies have established differences in which the female brain responds to ID-related neurochemical alterations versus the male brain, little is known about the interactions of dietary ID, Mn exposure, and sex on {gamma}-amino butyric acid (GABA). Male and female Sprague-Dawley rats were randomly divided into four dietary treatment groups: control (CN), control/Mn supplemented, ID, and ID/Mn supplemented. After 6 weeks of treatment, both ID diets caused a highly significant decrease in Fe concentrations across all brain regions compared to CN in both sexes. Both ID and Mn supplementation led to significant accumulation of Mn across all brain regions in both sexes. There was no main effect of sex on Fe or Mn accumulation. Striatal synaptosomes were utilized to examine the effect of dietary intervention on 3H-GABA uptake. At 4 weeks, there was a significant correlation between Fe concentration and 3H-GABA uptake in male rats (p < 0.05). At 6 weeks, there was a significant inverse correlation between Mn concentration and 3H-GABA uptake in male and female rats and a postitive correlation between Fe concentration and 3H-GABA uptake in female rats (p < 0.05). In conclusion, ID-associated Mn accumulation is similar in both sexes, with Mn levels affecting GABA uptake in both sexes in a comparable fashion.

Key Words: GABA; iron deficiency; manganese; rat; neurotoxicity.


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