Magnesium exerts both preventive and ameliorating effects in an in vitro rat Parkinson disease model involving 1-methyl-4-phenylpyridinium (MPP+) toxicity in dopaminergic neurons

Abstract

A study was conducted to clarify the effects of magnesium (Mg) administration in a rat Parkinson disease (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, K., Kawakami, E., Kikuchi-Horie, K., Ohara, K., Ogata, K., Takahama, S., Wada, M., Kihira, T., Yasui, M., 2006. Magnesium deficiency over generations in rats with special references to the pathogenesis of the parkinsonism-dementia complex and amyotrophic lateral sclerosis of Guam. Neuropathology 26, 115-128.]. The results indicated that Mg might protect dopaminergic neurons in the substantia nigra from degeneration. The concentration of Mg in the culture medium varied from 0.8 mM, corresponding to the control condition, to 4.0 mM. Effects were estimated by counting the number of surviving dopaminergic neurons immunopositive for tyrosine hydroxylase and measuring the length of dopaminergic neurites. An increase in the concentration of Mg to 1.2 mM significantly inhibited the toxicity of MPP+, and a concentration of 4.0 mM completely prevented any decrease in the number of dopaminergic neurons. The length of dopaminergic neurites was significantly preserved in the presence of Mg at 1.2 and 4.0 mM. An increase in the concentration of Mg to 1.2 and 4.0 mM led to a significant amelioration in the length of dopaminergic neurites after MPP+ toxicity. This is the first report to document a significant and striking effect of Mg for prevention of neurite and neuron pathology, and also amelioration of neurite pathology in a PD model.