AUTHOR=Zhu Lin , Lu Fangjin , Zhang Xiaoran , Liu Siyuan , Mu Ping 

TITLE=SIRT1 Is Involved in the Neuroprotection of Pterostilbene Against Amyloid β 25–35-Induced Cognitive Deficits in Mice

JOURNAL=Frontiers in Pharmacology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.877098

DOI=10.3389/fphar.2022.877098

ISSN=1663-9812

ABSTRACT=<p>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β (Aβ) deposits and neurofibrillary tangles. Pterostilbene (PTE), a bioactive component mainly in blueberries, is found to have neuroprotective properties. However, the specific underlying mechanisms of PTE in protecting AD remain unclear. Herein, we explored its effects on Aβ<sub>25–35</sub>-induced neuronal damage <italic>in vivo</italic> and <italic>in vitro</italic> and further compared the roles with its structural analog resveratrol (RES) in improving learning–memory deficits. We found that intragastric administration of PTE (40 mg/kg) displayed more effective neuroprotection on Aβ<sub>25–35</sub>-induced cognitive dysfunction assessed using the novel object test, Y-maze test, and Morris water maze test. Then, we found that PTE improved neuronal plasticity and alleviated neuronal loss both <italic>in vivo</italic> and <italic>in vitro</italic>. Additionally, PTE upregulated the expression of sirtuin-1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2) and the level of superoxide dismutase (SOD), and inhibited mitochondria-dependent apoptosis in the Aβ<sub>25–35</sub>-treated group. However, SIRT1 inhibitor EX527 reversed the neuroprotection and induced a drop in mitochondrial membrane potential in PTE-treated primary cortical neurons. Our data suggest that PTE’s enhancing learning–memory ability and improving neuroplasticity might be related to inhibiting mitochondria-dependent apoptosis via the antioxidant effect regulated by SIRT1/Nrf2 in AD.</p>