SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

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  • Sheng Gaofeng
    Department of Pharmacy, The Second Affiliated Hospital of Nantong University
  • Zhang Jinlin
    Department of Pharmacy, Affiliated Cancer Hospital of Nantong University
  • Gao Shengfeng
    Department of Pharmacy, The Second Affiliated Hospital of Nantong University
  • Gu Yuanyuan
    Department of Pharmacy, The Second Affiliated Hospital of Nantong University
  • Jiang Bo
    Department of Pharmacology, School of Pharmacy, Nantong University Department of Pharmacy, The Third Affiliated Hospital of Nantong University
  • Gao Qiufang
    Department of Pharmacology, School of Pharmacy, Nantong University Department of Pharmacy, The Third Affiliated Hospital of Nantong University

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<p>Patients with Alzheimer’s disease (AD) always have cognitive impairments. In this study we investigated whether 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) has improvements on cognitive dysfunction. The scopolamine model of dementia was used to investigate the anti-amnesic activities of SKF83959, and then, Western blotting and pharmacological inhibitor were used to assay the anti-amnesic mechanisms of SKF83959. It was found that SKF83959 administration significantly improved the scopolamine-induced memory impairments in the passive avoidance task, Y-maze test, and Morris water maze task. Moreover, SKF83959 treatment significantly antagonized the down-regulating effects of scopolamine on brain-derived neurotrophic factor (BDNF) signaling cascade in the hippocampus, but not cortex. Importantly, the usage of K252a, a selective inhibitor of tyrosine kinase B (TrkB), significantly attenuated the protective effects of SKF83959 in the scopolamine model. Collectively, this study shows that SKF83959 has beneficial effects in the scopolamine model of dementia by modulation of hippocampal BDNF signaling, implying a novel and potential therapeutic agent for treating dementia in AD.</p>

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