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Optical microscopic examination showed tau\u2010positive cells, atrophic neurons with darkly stained cytoplasms or swollen perikarya in the cerebrum, hippocampus and the brainstem of mice fed a low\u2010Ca\/Mg high\u2010Al 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\u2010mediated dUTP\u2010digoxigenin nick end\u2010labeling (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\u2010month\u2010experimental period and increased until the 25\u2010month\u2010experimental period. The present findings suggested that chronic exposure to a low\u2010Ca\/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\u2010Ca\/Mg high Al exposure might be one of the risk factors for the development of neuronal degeneration of ALS in the Kii Peninsula.<\/jats:p>","DOI":"10.1046\/j.1440-1789.2002.00441.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T15:07:53Z","timestamp":1047481673000},"page":"171-179","source":"Crossref","is-referenced-by-count":27,"title":["Chronic low\u2010Ca\/Mg high\u2010Al diet induces neuronal loss"],"prefix":"10.1111","volume":"22","author":[{"given":"Tameko","family":"Kihira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohei","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiro","family":"Yase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiitsu","family":"Ono","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoyoshi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,9,8]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.100"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-510X(97)00300-6"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1789.2001.00303.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(72)92903-0"},{"key":"e_1_2_6_6_2","first-page":"265","volume-title":"Amyotrophic Lateral Sclerosis in Asia and Oceania","author":"Garruto RM","year":"1984"},{"key":"e_1_2_6_7_2","first-page":"347","article-title":"Pacific paradigms of environmentally\u2010induced neurological disorders: clinical, epidemiological and molecular perspectives","volume":"12","author":"Garruto RM.","year":"1991","journal-title":"Neurotoxicology"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.1993.tb00222.x"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(95)00011-P"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)01297-U"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(97)00780-4"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197601222940402"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)92775-D"},{"key":"e_1_2_6_14_2","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1001\/archinte.1992.00400190071014","article-title":"Neurologic syndrome in 25 workers from an aluminum smelting plant","volume":"152","author":"White DM","year":"1992","journal-title":"Arch Intern Med"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00307634"},{"key":"e_1_2_6_16_2","unstructured":"LienEL BoyleFG WrennJM PerryRW ThompsonCA BorzellecaJF.Comparison of AIN\u201076A and AIN\u201093 diets: a 13\u2010week study in rats.Ciba Found Symp1992;169:5\u201325."},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00690191"},{"key":"e_1_2_6_18_2","volume-title":"Atlas of the Mouse Brain and Spinal Cord. 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