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ToxSci Advance Access published online on October 10, 2006

Toxicological Sciences, 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
Received August 21, 2006
Accepted October 6, 2006

Original Article

Brain Manganese Accumulation Is Inversely Related to GABA Uptake in Male and Female Rats

Joel G. Anderson 1, Paula T. Cooney 1, and Keith M. Erikson 1 *

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

* To whom correspondence should be addressed.
Keith M. Erikson, E-mail: kmerikso{at}uncg.edu


   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 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 GABA. Male and female Sprague-Dawley rats were randomly divided into four dietary treatment groups: control, control/Mn supplemented, ID, and ID/Mn supplemented. After six weeks of treatment, both ID diets caused a highly significant decrease in Fe concentrations across all brain regions compared to control 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 four weeks, there was a significant correlation between Fe concentration and 3H-GABA uptake in male rats (p<0.05). At six 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.

Keywords: GABA; Iron deficiency; Manganese; Rat; Neurotoxicity.
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