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 ca...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 ofβ-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 Aβlevels 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 ofβ-site amyloid precursor protein cleaving enzyme(the enzyme for Aβgeneration),and increased the levels of neprilysin(the enzyme for Aβdegradation)in the brain tissues of the aged mice.These results suggested that the chronic treatment with propofol might reduce brain Aβlevels potentially via decreasing brain levels ofβ-site amyloid precursor protein cleaving enzyme,thus decreasing Aβgeneration;and via increasing brain neprilysin levels,thus increasing Aβdegradation.These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research.展开更多
基金This research was supported by R21AG038994,RO1 GM088801 and RO1AG041274 from National lnstitutes of Health,Bethesda,Maryland,Investigator-initiated Research grant from Alzheimer's Association,Chicago,llinois,and Cure Alzheimer's Fund,Wellesley,Massachusetts to Zhongcong Xie.
文摘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 ofβ-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 Aβlevels 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 ofβ-site amyloid precursor protein cleaving enzyme(the enzyme for Aβgeneration),and increased the levels of neprilysin(the enzyme for Aβdegradation)in the brain tissues of the aged mice.These results suggested that the chronic treatment with propofol might reduce brain Aβlevels potentially via decreasing brain levels ofβ-site amyloid precursor protein cleaving enzyme,thus decreasing Aβgeneration;and via increasing brain neprilysin levels,thus increasing Aβdegradation.These preliminary findings from our pilot studies have established a system and postulated a new hypothesis for future research.
