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A female mouse model of amyotrophic lateral sclerosis parkinsonism dementia complex induced by cycad Wong, Margaret Chia-Ying

Abstract

Sex differences have been observed in amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis parkinsonism dementia complex (ALS-PDC). ALS-PDC patients present with a combination of ALS, AD and PD symptoms and neuropathology post mortem. Previous studies have provided evidence for a link between ALSPDC and cycad seed (Cycas micronesica) consumption. Cycad seed consumption has been shown to induce ALS-PDC features in adult male mice. In a series of experiments, the present study examined whether 1) cycad seed consumption induces ALS-PDC features in female mice, 2) if the human sex difference is reflected in the cycad mouse model and 3) if there is a sex difference, whether it is due to progesterone and estrogen. 7 month-old CD-1 female mice were fed either a control diet or cycad seed washed by traditional methods and tested for motor abilities measured by leg extension reflex, gait length and wire hang. Lumbar spinal cord tissue was stained for anti-active capase-3, GFAP, Fluoro-Jade B and cresyl violet. The effects of cycad feeding were also compared in intact females and intact males in the second experiment, and females that were intact, ovariectomized, or ovariectomized with hormone replacement in the third experiment. The same battery of motor tests used in the first experiment was applied to the second and third experiments. In the first experiment, deficits on the wire hang test were found in cycad-fed mice. However, differences were not found on the other motor tests or histological assessments unlike previous studies using males. It is concluded that consumption of cycad does not induce motor deficits and histopathology in female mice as was previously seen in males. Differences between male and female mice fed cycad were found on the leg extension and wire hang tests. Ovariectomized females were found to have an altered motor pattern on the gait length and wire hang tests compared to intact and ovariectomized + estrogen and progesterone replaced females. Due to lack of control groups, conclusions cannot be made about the second and third experiments. A discussion of experimental design is provided.

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