Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy

Abstract

Continuing analytical studies on environmental factors in the foci of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan and Guam, and metal analysis using neutron activation analysis in central nervous system (CNS) tissues from ALS cases indicate that chronic exposure to metals such as aluminum and manganese, together with a deficiency of minerals such as calcium and magnesium, may play a causative role in the neurodegeneration seen in ALS. An accurate and simple method for detecting minerals and trace metals in small, fresh samples of CNS tissue is necessary in order to follow the pathogenetic behavior of these elements. In this paper, we describe a method for measuring manganese (Mn) content in CNS tissue samples taken from mouse brain using inductively coupled plasma (ICP) spectroscopy and present results of the determination of Mn contents in spinal cord samples from ALS cases using the same method. ICP emission spectroscopy is considered to have great advantage for the simultaneous determination of elements in small, fresh CNS samples because of its simplicity and convenience, and the elimination of the necessity to use potentially dangerous acids. Results showed that the mean concentration of Mn in a mouse brain (0.56 μg/g) and in human spinal cords (0.39 μg/g wet weight in the anterior horn, 0.37 in the lateral fasciculus, 0.39 in the posterior horn and 0.28 in the posterior fasciculus) were compatible with results previously reported using other methods. In ALS spinal cords, the mean content of Mn was similar to that of controls, but the distribution differed. In the ALS cases, Mn contents were higher in the anterior horn and lateral fasciculus than in the posterior horn. A negative correlation between Mn and Ca contents was shown in the control spinal cords, but not in the ALS cords. Mn has been shown to inhibit neurotransmitter release with competitive inhibition of Ca in excitation-secretion coupling. Mn also activates calcium-activated neutral protease (CANP) under a disturbance of Ca metabolism. CANP probably controls the initial steps of intracellular protein degradation. It is speculated that an imbalance between Mn and Ca concentrations in the spinal cords of the ALS case may be associated with functional disability and neuronal death.