Magnesium and Calcium Contents in CNS Tissues of Amyotrophic Lateral Sclerosis Patients from the Kii Peninsula, Japan

Abstract

To further elucidate the involvement of metals as a factor in the pathogenesis of amyotrophic lateral sclerosis (ALS) on the Kii peninsula of Japan, a well-known high incidence area of ALS with low calcium and magnesium contents in soil and drinking water, we determined concentrations of these metals in samples of central nervous system tissue taken from postmortem ALS cases. Calcium content was determined by neutron activation analysis and magnesium by inductively coupled argon plasma emission spectrometry. From 5 ALS cases and 5 neurologically normal controls, we examined tissues from the precentral gyrus, including the motor cortex, internal capsule, cms cerebri and spinal cord, and from 22 other areas. The average calcium content in precentral gyrus, internal capsule, crus cerebri and spinal cord in ALS cases was higher than that in the controls, and the mean value of all 26 areas in the ALS cases was also higher than that of the controls. The average magnesium content of each region as well as the mean value of the 26 regions in the ALS cases was significantly lower than that in the controls. The Ca/Mg ratio of the 26 ALS regions was significantly higher than that of controls. This study strengthens our hypothesis that an abnormal metal metabolism plays a responsible role in the Ca-hydroxyapatite formation observed in central nervous system tissue of ALS cases, leading to motor neuron death and degeneration of the pyramidal tracts.

Molecular determinants of magnesium-dependent synaptic plasticity at electrical synapses formed by connexin36

“…Long-lasting elevation in brain [Mg 2+ ] i occurs in some acute and chronic brain pathologies such as hypoxia/ischemia 13 , 14 and in patients with schizophrenia 15 . In contrast, [Mg 2+ ] i is reduced after traumatic brain injury 16 , 17 and in patients with Parkinson 18 , Alzheimer 19 , multiple sclerosis 20 , amyotrophic lateral sclerosis 21 , chronic migraine 22 and mitochondrial diseases 23 .…”

Low Brain Intracellular Free Magnesium in Mitochondrial Cytopathies

“…Intracellular total and free magnesium concentration ([Mg 2+ ]) has been assessed in patients with some neurologic disorders (Ramadan et al, 1989; Taylor et al, 1991; Yasui and Ota, 1992; Yasui et al, 1992; Stelmiasiak et al, 1995; Welch and Ramadan, 1995; Lodi et al, 1997) and has been found to be decreased in multiple sclerosis (Yasui and Ota, 1992; Stelmiasiak et al, 1995), amyotrophic lateral sclerosis (Yasui et al, 1992), and migraine (Ramadan et al, 1989; Welch and Ramadan, 1995; Lodi et al, 1997). Therefore, deranged magnesium homeostasis could be involved in the pathogenesis of these diseases (Yasui and Ota, 1992; Yasui et al, 1992; Welch and Ramadan, 1995). The findings of low [Mg 2+ ] in migraine also has led to treatment of patients with magnesium, although with controversial results (Mauskop et al, 1996; Peikert et al, 1996; Pfaffenrath et al, 1996).…”

A critical review of the postulated role of the non-essential amino acid, β-N-methylamino-L-alanine, in neurodegenerative disease in humans

“…In addition, all treatment groups on the Ca deficient diets had significantly less Ca and Mg in the lumbar spine and femur when compared with controls. Garruto et al (1989) compared their findings and the Ca and Mg measurements in human CNS tissue found by Yasui, Yase, and Ota (1991a,1992) which were similar for Ca, but not Mg. Garruto et al (1989) further compared decreased bone density of rats with similar observations in Guam ALS patients and osteoporosis and aortic calcification seen in the population of the focus areas in Kii (Fujita et al 1984). Calcification of spinal ligaments is another condition related to Ca-Mg imbalance and in 1997, 120 cases were reported in the U.S., Europe, and Japan, and of those, 28 were residents from the Kii Peninsula (Yasui, Ota, and Yoshida 1997).…”

“…Yoshimasu et al (1976, 1980) found increased CNS Ca and Mg in 9/10 of the ALS cases and 2/3 of the Alzheimer cases, but not in the controls. Yasui et al (1991a, 1992) found increased Ca and/or Al and decreased Mg in the CNS of 7 ALS Kii patients. Yase (1972) cites a 1969 Yoshimasu publication which reported testing the Mn content in the CNS of three ALS patients, and three controls.…”