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Behavioural and neurotoxic effects of aluminum hydroxide and squalene adjuvants in relation to amyotrophic lateral sclerosis-gulf war illness

University of British Columbia

Gulf War Illness (GWI), more commonly known as Gulf War Syndrome, affects a significant percentage of veterans of the 1991 conflict, but its origins remain unknown. Associated with some cases of GWI are increased incidences of amyotrophic lateral sclerosis (ALS) and other neurological disorders. While many environmental factors have been linked to GWI, the role of the anthrax vaccine has come under increasing scrutiny. Among the vaccine’s potentially toxic components are the adjuvants aluminum hydroxide and squalene. To examine whether these compounds might contribute to neuronal deficits associated with GWI, I developed an animal model for examining the potential neurological impact of aluminum hydroxide, squalene, or aluminum hydroxide combined with squalene. Young male colony CD-l mice where injected with the adjuvants at doses equivalent to those given to U.S. military service personnel. All mice were subjected to a battery of behavioural (motor, cognitive and emotional) tests over a six-month period post injections. Following sacrifice, CNS tissues were examined using immunohistochemistry for evidence of inflammation and cell death. Behavioural testing showed motor deficits in the aluminum treatment group that expressed as a progressive decrease in strength measured by the wire mesh hang test (final deficit at 24 weeks: approx. 50%). Significant cognitive deficits in water maze learning in were observed in the combined aluminum and squalene group (4.3 errors/trial) compared to controls (0.2 errors/trial) after 20 weeks. Apoptotic neurons were identified in aluminum injected animals and showed significantly increased activated caspase-3 labeling in lumbar spinal cord (255%) and primary motor cortex (192%) compared to controls. Aluminum treated groups also showed significant motor neuron loss (35%) and increased numbers of 11 activated astrocytes (350%) in the lumbar spinal cord. Preliminary results from Iba-l staining showed microglial proliferation in lumbar spinal cord of aluminum treated animals. Morin staining detected the presence of the aluminum within the cell body and/or nucleus of neurons in this same area. The findings suggest a possible role for the aluminum adjuvant in some neurological features associated with GWI and possibly an additional role for the combination of adjuvants.

Text

2010-01-13

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http://hdl.handle.net/2429/18110

Neuroscience

University of British Columbia

UBCV

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