长期的 gabapentin 治疗通过 tau 过酸化损害了老年小鼠的认知功能
Suyun Xia1,2, Zerong You2,3, Xinbo Wu2,4
1Department of Anesthesiology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Frontiers in pharmacology
|September 19, 2025
概括
长期使用 gabapentin (GBP) 会通过降低 Sirt1 表达和增加 tau 酸化而损害老年小鼠的记忆力. 提高Sirt1活动可以防止这种认知衰退.
科学领域:
- 神经科学是一个神经科学.
- 老年学是一门学科.
- 药理学 药理学是指药理学的学科.
背景情况:
- 加巴丁 (GBP) 经常用于治疗老年人的疼痛.
- 最近的证据表明,英对老年人的认知功能有负面影响.
- 英对衰老的认知影响的精确分子机制尚不清楚.
研究的目的:
- 研究加巴丁对老年人认知功能不良影响背后的分子机制.
- 探索Sirt1和陶酸化在 gabapentin 诱导的认知障碍中的作用.
- 评估针对Sirt1的潜在治疗策略,以减轻 gabapentin 的副作用.
主要方法:
- 老老鼠接受了神经损伤 (SNI) 或假手术,并接受了 gabapentin (GBP) 治疗.
- 使用新型对象识别 (NOR) 和恐惧条件测试 (FCT) 评估认知功能.
- 分析海马组织的p-tau,CaMKIIα和Sirt1水平;通过AAV使用过度基因表达.
主要成果:
- 长期的GBP治疗导致老年小鼠的学习和记忆受损,无论疼痛状态如何.
- GBP治疗导致海马体p-tau (S416,S262) 和CaMKIIα增加,Sirt1表达减少.
- 过度表达Sirt1或使用白醇可逆转GBP诱导的认知缺陷和陶过酸化.
结论:
- 长期的 gabapentin 管理对老年小鼠的认知功能产生不利影响.
- GBP抑制了Sirt1,增加了CaMKIIα和的过酸化,导致记忆障碍.
- 增强Sirt1活动有效地抵消了 gabapentin 在衰老中的负面认知影响.
相关概念视频
01:22Pharmacokinetics in Geriatric Patients: Effect of Age on Drug Absorption
229
As individuals age, their body's physiology evolves, affecting drug pharmacokinetics. The most apparent changes occur in the gastrointestinal tract, where an increase in gastric pH, a delay in gastric emptying, and a reduction in gastrointestinal motility are observed. Remarkably, these changes do not substantially modify the absorption of orally administered drugs, particularly those absorbed via passive diffusion.Transdermal drug delivery emerges as a highly viable method for older adults due...
229
01:22Alzheimer's Disease: Treatment
825
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
825
01:27Pharmacodynamics in Geriatric Patients: Effects of Age
188
Age-related pharmacokinetic changes are extensively documented, but understanding age-related pharmacodynamic alterations is relatively limited. This knowledge gap can be partly attributed to the complexity of developing appropriate measures of drug responses compared to bioanalytical methods for determining drug concentrations.Most information regarding age-related differences in human pharmacodynamics originates from cross-sectional studies. However, these studies assume that observed mean...
188