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.
Subject(s)
Amyotrophic Lateral Sclerosis/pathology , Brain/pathology , Dementia/pathology , Parkinson Disease/pathology , Prenatal Exposure Delayed Effects , Amyotrophic Lateral Sclerosis/physiopathology , Animals , Calcium/deficiency , Dementia/physiopathology , Diet , Female , Guam , Magnesium Deficiency/pathology , Magnesium Deficiency/physiopathology , Male , Nerve Degeneration/etiology , Nerve Degeneration/pathology , Neurons/pathology , Parkinson Disease/physiopathology , Pregnancy , Rats , Rats, WistarABSTRACT
A condition of unbalanced minerals was found in soil and drinking water from three amyotrophic lateral sclerosis (ALS) foci on Guam, in the Kii Peninsula and in West New Guinea with a low concentration of calcium and magnesium coupled with a high concentration of aluminum and manganese. The current epidemiological studies in the Western Pacific including the Kii Peninsula of Japan, have suggested that environmental factors contribute to the pathogenetic process of ALS and parkinsonism-dementia (PD). Six Kii cases with ALS showed higher Ca and lower Mg contents in the central nervous system (CNS) tissues than those of neurologically normal controls. We subsequently designed an animal study to experimentally ascertain the mineral or metal deposition in CNS tissues under various dietary regimens using rats. The experimental results suggest that unbalanced minerals and/or metals lead to the accumulation not only of Ca, but also Mn, and Al, and diminution of Mg and Zn in CNS tissues of rats and humans on these dietary regimens, with implication for long-term neuronal degeneration and accumulating CNS deficit.
