L-3-n-Butylphthalide Effectively Improves the Glymphatic Clearance and Reduce Amyloid-β Deposition in Alzheimer's Transgenic Mice

摘要

Amyloid-beta (A beta) deposit in the parenchyma is a major characteristic in Alzheimer's disease (AD), and the impaired glymphatic clearance contributes to the A beta accumulation. It was reported that L-3-n-butylphthalide (NBP) showed the potential neuroprotective effect in the rodent models of AD. The effects of NBP on the glymphatic system were explored in this study. In the wild-type mice, both CSF tracer influx and perivascular drainage increased after NBP treatment compared with vehicle treatment. Moreover, NBP promoted the perivascular drainage of A beta via increased cerebral pulsation, which could be inhibited by propranolol. Then, we studied the potential of 3-month NBP treatment on A beta deposits in 8-month-old APP/PS1 transgenic mice. NBP daily treatments remarkably improved cognitive behavior in Morris water maze. Furthermore, NBP could reduce A beta deposition and decrease parenchymal A beta levels. In addition, NBP markedly improved the perivascular AQP4 localization. Our results indicated that NBP could enhance the glymphatic clearance and reduce parenchymal A beta deposit in the APP/PS1 mice, suggesting that it may have potential in the treatment of AD.

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