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Effects of manganese exposure and iron deficiency on the biology of GABA and norepinephrine

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Joel G. Anderson (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Keith Erikson

Abstract: Both manganese (Mn) and iron (Fe) are dietary metals required for numerous important processes in mammalian systems, and disturbances in the homeostasis of these metals can have deleterious effects, specifically on the central nervous system. In these studies, weanling-male Sprague-Dawley rats were randomly placed into one of four dietary treatment groups: control (CN; 35 mg Fe/kg diet), iron-deficient (ID; 6 mg Fe/kg diet), CN with Mn exposure (via the drinking water; 1 g Mn/L) (CNMn), and ID with Mn exposure (IDMn). Iron deficiency affected 3H-GABA uptake in male rats after four weeks of exposure and females after six weeks, demonstrating sex difference in the response to dietary ID in terms of a neurochemical outcome. ID-associated Mn accumulation was similar in the brains of both male and female rats, as was an inverse relationship between Mn and 3H-GABA uptake observed in both sexes at six weeks supporting previous data illustrating disturbances in GABA levels as a result of Mn exposure. 3H-NE uptake decreased significantly with increased Mn concentration in the locus coeruleus, while decreased Fe was associated with decreased uptake of 3H-NE in the caudate putamen and locus coeruleus. Using in vivo microdialysis, an increase in extracellular GABA concentrations in the striatum was observed in response to Mn exposure and ID although correlational analysis reveals that extracellular GABA is related more to extracellular iron levels and not Mn. Extracellular concentrations of NE in the caudate putamen were significantly decreased in response to Mn exposure and ID. A diverse effect of Mn exposure and ID was observed in the regions examined via Western blot and RT-PCR analysis, with effects on mRNA and protein expression of GAT-1, GABAA, GABAB, NET, and <&alpha> 2 adrenergic receptor differing between and within the regions examined. These data not only illuminate the multifaceted nature of Mn toxicity in relation to the neurotransmitter systems involved, but also illustrate the complex dynamic between Mn and Fe levels. This information increases the understanding of the etiology of Mn toxicity and could potentially aid in the development of therapies for vulnerable populations (e.g., ID individuals and Mn-exposed workers).

Additional Information

Publication
Dissertation
Language: English
Date: 2009
Keywords
Manganese Exposure, Iron Deficiency, Biology, GABA
Subjects
Manganese $x Physiological effect.
Iron deficiency anemia.
GABA $x Receptors.
Neurotransmitter receptors.
Sprague Dawley rats $x Research.