4.6 Article

Aluminum hydroxide injections lead to motor deficits and motor neuron degeneration

期刊

JOURNAL OF INORGANIC BIOCHEMISTRY
卷 103, 期 11, 页码 1555-1562

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2009.05.019

关键词

Aluminum hydroxide; Adjuvant; Neurotoxicity; Gulf War Syndrome; Amyotrophic lateral sclerosis

资金

  1. Scottish Rite Charitable Foundation of Canada
  2. Natural Science and Engineering Research Council of Canada

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Gulf War Syndrome is a multi-system disorder afflicting many veterans of Western armies in the 19901991 Gulf War. A number of those afflicted may show neurological deficits including various cognitive dysfunctions and motor neuron disease, the latter expression virtually indistinguishable from classical amyotrophic lateral sclerosis (ALS) except for the age of onset. This ALS cluster represents the second such ALS cluster described in the literature to date. Possible causes of GWS include several of the adjuvants in the anthrax vaccine and others. The most likely culprit appears to be aluminum hydroxide. In an initial series of experiments, we examined the potential toxicity of aluminum hydroxide in male, outbred CD-1 mice injected subcutaneously in two equivalent-to-human doses. After sacrifice, spinal cord and motor cortex samples were examined by immunohistochemistry. Aluminum-treated mice showed significantly increased apoptosis of motor neurons and increases in reactive astrocytes and microglial proliferation within the spinal cord and cortex. Morin stain detected the presence of aluminum in the cytoplasm of motor neurons with some neurons also testing positive for the presence of hyper-phosphorylated tau protein, a pathological hallmark of various neurological diseases, including Alzheimer's disease and frontotemporal dementia. A second series of experiments was conducted on mice injected with six doses of aluminum hydroxide. Behavioural analyses in these mice revealed significant impairments in a number of motor functions as well as diminished spatial memory capacity. The demonstrated neurotoxicity of aluminum hydroxide and its relative ubiquity as an adjuvant suggest that greater scrutiny by the scientific community is warranted. (C) 2009 Elsevier Inc. All rights reserved.

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