Magnesium deficiency over generations in rats with special references to the pathogenesis of the parkinsonism–dementia complex and amyotrophic lateral sclerosis of Guam

Abstract

Parkinsonism-dementia complex (PDC) and amyotrophic lateral sclerosis (ALS) are fatal neurological diseases. The incidence on Guam was very high between 1950 and 1965 but decreased dramatically after 1965. It is thought that drinking water containing low levels of calcium (Ca) and magnesium (Mg), and high levels of aluminum and of a plant excitatory neurotoxin are involved in the pathogenesis of these diseases. The present experiment was performed in rats that were exposed to low Ca and/or Mg intake over two generations, thus simulating the conditions of human life on Guam, where several generations live continuously in the same environment. Significant loss of dopaminergic neurons was identified exclusively in the substantia nigra in 1-year-old rats that had been exposed continuously to low Mg intake (one-fifth of the normal level) over generations. The present study suggests that low Mg intake over generations may be involved in the pathogenesis of substantia nigra degeneration in humans.

Magnesium in the Central Nervous System

“…Experimental findings supported this hypothesis: animals fed diets that mimic the mineral composition in the disease foci environment showed signs of neuronal damage; of the various combinations of Ca 2+ and Mg 2+ contents tested, exposure to low Mg 2+ (one--fifth of the normal level) was more deleterious, causing significant loss of dopaminergic neurons in the substantia nigra (Oyanagi et al, 2006). Furthermore, motor neurons are selectively more vulnerable to L--BMAA toxicity, and these toxic effects are mediated through [Ca 2+ ] i rises via Ca--A/K channels and other pathways, and subsequent reactive oxygen species generation (Rao et al, 2006).…”

“…Scheme of possible pathomechanisms of dopaminergic neuron death in Parkinson's disease. (Oyanagi et al, 2006). This finding suggested a deep concern of low Mg intake over several generations to the pathogenesis of degeneration of the substantia nigra in humans.…”

“…Continuous low Mg intake for two generations induces exclusive loss of dopaminergic neurons in rats , and may support the Mg hypothesis in the pathogenesis of parkinsonism--dementia complex (PDC) of Guam. Mg supple--mentation prevents the loss of dopaminergic neurons and ameliorates neurite pathology in a PD model, indicating a role of Mg in protection of dopaminergic neurons in the substantia nigra from degeneration (Oyanagi et al, 2006;Hashimoto et al, 2008). Also, Mg at concentrations > 0.75 mM inhibits the aggregation of α--synuclein, induced either spontaneously or by incubation with iron .…”

“…The present authors conducted a study to clarify the effects of Mg administration in a rat PD model involving culture of ventral mesencephalic--striatal cells with 1--methyl--4--phenylpyridinium (MPP + ), based on recent evidence for significant loss of dopaminergic neurons exclusively in the substantia nigra of 1--year--old rats after exposure to low Mg intake over generations (Oyanagi et al, 2006) (Figure 6). The results indicated that Mg might protect dopaminergic neurons in the substantia nigra from degeneration.…”

“…Figure 6. Severe atrophy and selective loss of dopaminergic neurons in the substantia nigra in rats with low Mg over generations (Oyanagi K, et al, 2006).…”