Chronic low-Ca/Mg high-Al diet induces neuronal loss.

To evaluate the causative role of environmental aluminum (Al) in the development of neurodegeneration in Kiiamyotrophic lateral sclerosis (ALS), we examined how chronic exposure to a low-Ca/Mg and high-Al diet induced neuronal loss and tau-related neuronal degeneration in experimental animals. Optical microscopic examination showed tau-positive cells, atrophic neurons with darkly stained cytoplasms or swollen perikarya in the cerebrum, hippocampus and the brainstem of mice fed a low-Ca/Mg high-Al diet (Group 3). The neuronal loss was found in the frontal and parietal cortices of the mice and was not due to a classical apoptosis as detected by the terminal de ynucl otidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Neuronal degeneration and spheroid formation was also seen in the spinal cord of the Group 3 mice. The Morin fluorescence technique showed Al and Ca deposition in the cortical neurons and vessels in the basal ganglia of these mice. An electron microscopic examination showed intranuclear filamentous structures, intracytoplasmic vacuoles and/or darkly stained cytoplasm in the cortical neurons of Group 3 mice. These findings were seen in mice of the 11-month-experimental period and increased until the 25-month-experimental period. The present findings suggested that chronic exposure to a low-Ca/Mg high Al condition induced an accumulation of hyperphosphorylated tau in the cortical neurons, swelling of the neuronal cytoplasm and loss in the cerebrum and spinal cord of mice. Environmental factors such as a low-Ca/Mg high Al exposure might be one of the risk factors for the development of neuronal degeneration of ALS in the Kii Peninsula.