WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice

Xu, Hui; You, Zhengchen; Wu, Zhiyong; Zhou, Liang; Shen, Jianhong; Gu, Zhifeng

doi:10.1007/s11064-016-2002-1

Cited by 12 publications

(20 citation statements)

References 46 publications

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Section: Methodsmentioning

confidence: 99%

“…The dosages of these compounds were chosen according to previous reports. 12,15,16) For drug administration, intraperitoneally (i.p.) injected in a volume of 10 mL/kg was employed.…”

Section: Methodsmentioning

confidence: 99%

“…[15][16][17] The training trial was performed 24 h before the test trial. The equipment has two identical chambers with one illuminated and the other non-illuminated.…”

Section: Methodsmentioning

confidence: 99%

“…15,16) In this study, we also employ this model to investigate whether SKF83959 has anti-amnesic effects.…”

Section: )mentioning

confidence: 99%

“…The housing environment was set as described. 12,15,16) All the procedures involving mice were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (8th edition, Institute of Laboratory Animal Resources on Life Sciences, National Research Council, National Academy of Sciences, Washington DC, U.S.A.), and approved by the Lab Animal Ethical Committee of Nantong University.Drugs and Treatments SKF83959 (0.5, 1 mg/kg; Tocris Bioscience, Bristol, U.K.), donepezil (5 mg/kg; Sigma, St. Louis, MO, U.S.A.), scopolamine (1 mg/kg; Sigma) and K252a (25 µg/kg; Alomone Laboratories, Jerusalem, Israel) were all dissolved in 1% dimethyl sulfoxide (DMSO) in 0.9% saline. The dosages of these compounds were chosen according to previous reports.…”

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confidence: 99%

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SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

Sheng

Zhang

Gao

et al. 2018

Biological & Pharmaceutical Bulletin

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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.Key words brain-derived neurotrophic factor; memory; scopolamine; SKF83959 As a world-wide neurodegenerative disease, Alzheimer's disease (AD) causes huge damage to our society.1) In clinical, patients with AD always have dementia, meaning the loss of memory.2,3) Dementia is very common in older persons, and leads to severe interference in occupational and social performance. Current researches have revealed that patients with AD have severe cholinergic dysfunction in the brain, [4][5][6] and some cholinergic antagonists, especially scopolamine, have been shown to induce memory impariments in rodents. 7) In contrast, some acetylcholinesterase inhibitors (AChEIs), such as donepezil, were developed for AD therapy in clinical. However, current AChEIs used clinically have various adverse effects including diarrhea, insomnia and vomiting, and their efficacy are not very good.8) Therefore, developing novel therapeutic agents to treat dementia in AD is very necessary.6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is one compound which belongs to benzazepine family and has been acknowledged as a selective D 1 -D 2 heteromer agonist. Until now, a lot of reports have been showing the effects of SKF83959 on the brain. For example, Wu et al. showed that SKF83959 has protective effects against neuroinflammation. 9)Chu et al. reported that SKF83959 has promoting effects on neuronal release of glutamate. 10) Zhang et al. found that SKF83959 administration has beneficial and reversing effects in the 6-hydroxy-dopamine (6-OHDA) model of Parkinson's disease. 11) We noticed that in 2014, Jiang et al. demonstrated the antidepressant effects of SKF83959 in mice which were mediated through activating the brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (Tr...

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Section: Methodsmentioning

confidence: 99%

“…The dosages of these compounds were chosen according to previous reports. 12,15,16) For drug administration, intraperitoneally (i.p.) injected in a volume of 10 mL/kg was employed.…”

Section: Methodsmentioning

confidence: 99%

“…[15][16][17] The training trial was performed 24 h before the test trial. The equipment has two identical chambers with one illuminated and the other non-illuminated.…”

Section: Methodsmentioning

confidence: 99%

“…15,16) In this study, we also employ this model to investigate whether SKF83959 has anti-amnesic effects.…”

Section: )mentioning

confidence: 99%

mentioning

confidence: 99%

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SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

Sheng

Zhang

Gao

et al. 2018

Biological & Pharmaceutical Bulletin

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Pharmaco-fUS: Quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice

Rabut

Ferrier

Bertolo³

et al. 2020

NeuroImage

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Sesamol Attenuates Scopolamine-Induced Cholinergic Disorders, Neuroinflammation, and Cognitive Deficits in Mice

Yun

Wang

Zhang

et al. 2022

J. Agric. Food Chem.

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Alzheimer’s disease (AD) is a neurodegenerative disease, characterized by memory loss and cognitive deficits accompanied by neuronal damage and cholinergic disorders. Sesamol, a lignan component in sesame oil, has been proven to have neuroprotective effects. This research aimed to investigate the preventive effects of sesamol on scopolamine (SCOP)-induced cholinergic disorders in C57BL/6 mice. The mice were pretreated with sesamol (100 mg/kg/d, p.o.) for 30 days. Behavioral tests indicated that sesamol supplement prevented SCOP-induced cognitive deficits. Sesamol enhanced the expression of neurotrophic factors and postsynaptic density (PSD) in SCOP-treated mice, reversing neuronal damage and synaptic dysfunction. Importantly, sesamol could balance the cholinergic system by suppressing the AChE activity and increasing the ChAT activity and M1 mAChR expression. Sesamol treatment also inhibited the expression of inflammatory factors and overactivation of microglia in SCOP-treated mice. Meanwhile, sesamol improved the antioxidant enzyme activity and suppressed oxidative stress in SCOP-treated mice and ameliorated the oxidized cellular status and mitochondrial dysfunction in SCOP-treated SH-SY5Y cells. In conclusion, these results indicated that sesamol attenuated SCOP-induced cognitive dysfunction via balancing the cholinergic system and reducing neuroinflammation and oxidative stress.

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WY14643 Attenuates the Scopolamine-Induced Memory Impairments in Mice

Cited by 12 publications

References 46 publications

SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

SKF83959 Has Protective Effects in the Scopolamine Model of Dementia

Pharmaco-fUS: Quantification of pharmacologically-induced dynamic changes in brain perfusion and connectivity by functional ultrasound imaging in awake mice

Sesamol Attenuates Scopolamine-Induced Cholinergic Disorders, Neuroinflammation, and Cognitive Deficits in Mice

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