Possible Interaction: Gamma-Aminobutyric Acid and Manganese

“Several in vivo and in vitro studies have linked increased manganese concentrations with alterations in the content and metabolism of neurotransmitters, namely dopamine, gamma-aminobutyric acid , and glutamate.”

“Neurochemically, the initial neurotoxic effect of Mn is the perturbation of striatal γ-aminobutyric acid levels.”

“ Manganese concentrations increased in the striatum, the rest of the brain, and in plasma, and regional brain neurotransmitter concentrations, including noradrenaline, dopamine (DA), 5-hydroxytrytamine, glutamate, taurine, and γ-amino butyric acid , and the activity of acetylcholinesterase changed.”

“Furthermore, control cells exposed to Mn only during the experimental uptake had significantly reduced (3)H-GABA uptake, and the addition of GABA (50 μM) blunted cytosolic Mn accumulation.”

“ Manganese (Mn) exposure interferes with GABA uptake; however, the effects of Mn on GABA transport proteins (GATs) have not been identified.”

“Loss of the plasma membrane GABA transporter SNF-11, as well as acute photoevoked GABA release, affected cholinergic MN function in opposite directions.”

“Available evidence in rodents suggests that Mn causes dysregulation of glutamatergic and gamma-aminobutyric acidergic ( GABAergic ) neurotransmitter systems.”

“Previous data from our lab have shown decreased brain tissue levels of GABA as well as decreased (3)H-GABA uptake in synaptosomes as a result of Mn exposure and ID.”

“These data suggest that Mn exposure results in an increase in extracellular GABA concentrations via altered expression of transport and receptor proteins, which may be the basis of the neurological characteristics of manganism.”

“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.”

“ Gamma amino butyric acid concentrations were increased in the globus pallidus (GP) with manganese exposure.”

“The striatum is particularly vulnerable, for there is a significant negative correlation between accumulated manganese and gamma-aminobutyric acid levels.”

“ Manganese did not affect striatal dopamine, but resulted in significant increases in striatal y-aminobutyric acid ( GABA ) of 16 and 22% (P < 0.01) in both striati and a borderline non-significant 4% increase in frontal cortex (P = 0.076).”