ST09, a Novel Thioester Derivative of Tacrine, Alleviates Cognitive Deficits and Enhances Glucose Metabolism in Vascular Dementia Rats

Autor: Peng-Fei Wu, Li-Hong Long, Han Luo, Jun Zhou, Zu-Cheng Shen, Fang Wang, Qing-Guo Xie, Jian-Min Liu, Jing Rao, Jian-Guo Chen, Fengchao Jiang, Jian-Geng Huang, Xiao Liang
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Niacinamide
Aché
Hippocampus
Apoptosis
Pharmacology
In Vitro Techniques
medicine.disease_cause
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Fluorodeoxyglucose F18
Physiology (medical)
medicine
Animals
Pharmacology (medical)
Vascular dementia
Donepezil
Maze Learning
Active metabolite
Nootropic Agents
Cell Line
Transformed
Cerebral Cortex
Dose-Response Relationship
Drug
Chemistry
Dementia
Vascular
Electron Spin Resonance Spectroscopy
Original Articles
medicine.disease
Acetylcholinesterase
language.human_language
Rats
Psychiatry and Mental health
Disease Models
Animal
030104 developmental biology
Glucose
Tacrine
language
Cognition Disorders
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
medicine.drug
Popis: Summary Aims Chemical entities containing mercapto group have been increasingly attractive in the therapy of central nerve system (CNS) diseases. In the recent study, we screened a series of mercapto-tacrine derivatives with synergistic neuropharmacological profiles in vitro. Methods We investigated the effect and mechanism of ST09, a thioester derivative of tacrine containing a potential mercapto group, on the vascular dementia (VaD) model of rat induced by bilateral common carotid arteries occlusion (2-VO). Results ST09 and its active metabolite ST10 retained excellent inhibition on acetylcholinesterase (AChE) activity. ST09 significantly attenuated the 2-VO-induced impairment in spatial acquisition performance and inhibited the 2-VO-induced rise of AChE activity. In the VaD model, ST09 attenuated the oxidative stress and decreased the apoptosis in the cortex and hippocampus. Compared with donepezil, ST09 exhibited a better effect on the regeneration of free thiols in 2-VO rats. Interestingly, ST09, not donepezil, greatly improved glucose metabolism in various brain regions of 2-VO rats using functional imaging of 18F-labeled fluoro-deoxyglucose (FDG) positron emission tomography (PET). Conclusions ST09 may serve as a more promising agent for the therapy of VaD than tacrine owing to the introduction of a potential mercapto group into the parent skeleton.
Databáze: OpenAIRE
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