To equanimous: Excitotoxicity and manganese

Discussion in 'Fibromyalgia Main Forum' started by richvank, Jan 14, 2011.

  1. richvank

    richvank New Member

    Hi, Liz.

    One thing I didn't mention before is that the enzyme glutamine sythetase, which converts glutamate to glutamine in the astrocytes of the brain, requires manganese. So if there is a manganese deficiency, that could also promote excitotoxicity. See the abstract below.


    Neurotoxicology. 1999 Apr-Jun;20(2-3):173-80.
    Manganese uptake and distribution in the central nervous system (CNS).

    Aschner M, Vrana KE, Zheng W.

    Department of Physiology and Pharmacology, Wake Forest University School of Medicine of Wake Forest University, Winston-Salem, NC, USA.

    Information about the nature of manganese (Mn)-binding ligands in plasma and serum, and its transport mechanism across the blood-brain barrier (BBB) is sparse. Most studies to date have focused on distribution, excretion, and accumulation of intravenous and intraperitoneal solutions of soluble divalent salts of Mn. Mn is transported in the blood primarily in the divalent oxidation state (Mn2+) and crosses the BBB via specific carriers at a rate far slower than in other tissues. Mn transport across the BBB occurs both in the 2+ and 3+ oxidation state. Within the CNS, Mn accumulates primarily within astrocytes, presumably because the astrocyte-specific enzyme, glutamine synthetase (GS), represents an important regulatory target of Mn. Compared to Mn2+, Mn3+ has a slower elimination rate and therefore, may have a greater tendency to accumulate in tissues. Furthermore, in view of the dependence of Mn accumulation within the CNS on iron (Fe) homeostasis, the oxidation state of Mn may represent a key determinant in the differential distribution, accumulation and secretion profiles of Mn, a fact that has received little attention in experimental biology toxicology. Accordingly, the distribution and membrane transport of Mn emphasizes the importance of: 1) the oxidation state of Mn, as it governs the affinity of Mn to endogenous ligands, and 2) the reaction of Mn3+ with transferrin, the plasma iron-carrying protein. This review will focus on transport kinetics of Mn across the BBB (both in the 2+ and 3+ oxidation state), the putative role of transferrin in the transport of Mn across the BBB, the transport of Mn by astrocytes, as well as the physiological significance of Mn to the function GS.

    PMID: 10385881 [PubMed - indexed for MEDLINE]
  2. equanimous

    equanimous New Member

    Thanks for this extra info. It never would have occurred to me. Not sure how to tell if my manganese might be too low without getting tested for it. Just from reading about it briefly, it seems like it could be dangerous to supplement if I don't really need it since it's only required in extremely minute quantities. I will keep this in mind though.

  3. richvank

    richvank New Member

    Hi, Liz.

    It's true that manganese is toxic at high enough levels. It's also true that manganese is one of the essential minerals for the human body. Beside its support of glutamine synthetase, it is also found in the mitochondrial form of superoxide dismutase (SOD2). This enzyme is important for controlling oxidative stress. It is needed by other enzymes as well.

    The toxicity of manganese was discovered by studying its effects on workers in a factory that processed manganese oxide. In those days, little attention was paid to limiting exposure. The workers' bodies were coated with black manganese oxide. They were inhaling the dust, and swallowing it as well. Over time, they developed a Parkinson's-like neurological disorder.

    The Institute of Medicine has recommended a safe upper limit dosage of 11 milligrams per day.

    Best regards,

  4. Perrier

    Perrier New Member

    I tried to email you and the address did not work.

    Is there an email address where i could reach you?