Abstract
This study determined whether antioxidant supplementation is a viable complement to exercise regimens in improving cognitive and motor performance in a mouse model of Alzheimer’s disease risk. Starting at 12 months of age, separate groups of male and female mice expressing human Apolipoprotein E3 (GFAP-ApoE3) or E4 (GFAP-ApoE4) were fed either a control diet or a diet supplemented with vitamins E and C. The mice were further separated into a sedentary group or a group that followed a daily exercise regimen. After 8 weeks on the treatments, the mice were administered a battery of functional tests including tests to measure reflex and motor, cognitive, and affective function while remaining on their treatment. Subsequently, plasma inflammatory markers and catalase activity in brain regions were measured. Overall, the GFAP-ApoE4 mice exhibited poorer motor function and spatial learning and memory. The treatments improved balance, learning, and cognitive flexibility in the GFAP-ApoE3 mice and overall the GFAP-ApoE4 mice were not responsive. The addition of antioxidants to supplement a training regimen only provided further benefits to the active avoidance task, and there was no antagonistic interaction between the two interventions. These outcomes are indicative that there is a window of opportunity for treatment and that genotype plays an important role in response to interventions.
Highlights
Apolipoprotein E4 (ApoE4) is the most prevalent genetic risk factor for late-onset Alzheimer’s disease (AD) [1]
The female groups, glial fibrillary acidic protein (GFAP)-ApoE4 mice weighed less than the GFAP-ApoE3 mice
By week 7, most mice lost 3–7% of their body weight, and the only significant differences differences were between E3 and E4 sedentary + control diet (Sed-Con) females, and between Sed-Con and Sed-Aox in the were between E3 and E4 Sed-Con females, and between Sed-Con and Sed-Aox in the GFAP-ApoE4
Summary
Apolipoprotein E4 (ApoE4) is the most prevalent genetic risk factor for late-onset Alzheimer’s disease (AD) [1]. In mice expressing human ApoE4, the cognitive deficits can be measured in terms of impairments in spatial learning and memory [2] and working memory [3]. Apart from cognitive declines, other behavioral effects are associated with AD and preclinical AD, such as increased anxiety [4], motor function disability, and the inability to learn new motor skills [5,6]. The presence of the ε4 allele was associated with a two-fold increase in the rate of global motor function decline when compared with non-carriers with comparable age, sex, and education [7]. Oxidative stress has been associated with cognitive and motor declines and has been suggested as a major contributor to AD pathology. Oxidative stress has been involved in vascular cognitive impairment, a risk for dementia [8]. ApoE4 is associated with the Antioxidants 2020, 9, 553; doi:10.3390/antiox9060553 www.mdpi.com/journal/antioxidants
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