Abstract
Alzheimer’s disease (AD) is the most common form of dementia. At the present time, however, AD still lacks effective treatments. Our recent studies showed that chronic treatment with anesthetic propofol attenuated brain caspase-3 activation and improved cognitive function in aged mice. Accumulation of β-amyloid protein (Aβ) is a major component of the neuropathogenesis of AD dementia and cognitive impairment. We therefore set out to determine the effects of chronic treatment with propofol on Aβ levels in brain tissues of aged mice. Propofol (50 mg/kg) was administrated to aged (18 month-old) wild-type mice once a week for 8 weeks. The brain tissues of mice were harvested one day after the final propofol treatment. The harvested brain tissues were then subjected to enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Here we report that the propofol treatment reduced Aβ (Aβ40 and Aβ42) levels in the brain tissues of the aged mice. Moreover, the propofol treatment decreased the levels of β-site amyloid precursor protein cleaving enzyme (the enzyme for Aβ generation), and increased the levels of neprilysin (the enzyme for Aβ degradation) in the brain tissues of the aged mice. These results suggested that the chronic treatment with propofol might reduce brain Aβ levels potentially via decreasing brain levels of β-site amyloid precursor protein cleaving enzyme, thus decreasing Aβ generation; and via increasing brain neprilysin levels, thus increasing Aβ degradation. These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research.
Highlights
Alzheimer disease (AD) is an insidious and progressive neurodegenerative disorder accounting for the vast majority of dementia, and is characterized by global cognitive decline and the robust accumulation of amyloid deposits and neurofibrillary tangles in the brain
The enzyme-linked immunosorbent assay (ELISA) studies showed that the brain tissues from the propofol-treated mice had lower levels of Aβ40 as compared to the brain tissues from the saline-treated mice: 42 versus 78 pg/ 1 mg protein, P = 0.027 (Figure 1A)
Our recent studies have shown that a weekly treatment with 50 mg/kg propofol for 8 weeks is able to improve the cognitive function in the aged mice, and reduces caspase-3 activation in the brain tissues of the mice [22]
Summary
Alzheimer disease (AD) is an insidious and progressive neurodegenerative disorder accounting for the vast majority of dementia, and is characterized by global cognitive decline and the robust accumulation of amyloid deposits and neurofibrillary tangles in the brain (reviewed in [1]). Given Aβ accumulation can lead to cognitive impairment [reviewed in [1]), we set out in the present pilot studies to establish a system and to test a hypothesis that the chronic treatment with propofol can decrease Aβ levels in the brain tissues of aged mice via inhibiting its generation and/or promoting its degradation. The findings from these proof of concept studies would promote more research to further determine the effects of anesthetic propofol on AD neuropathogenesis
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