Tucker Matthew, Keely Addison, Park Joo Young, Rosenfeld Manuela, Wezeman Jackson, Mangalindan Ruby, Ratner Dan, Ladiges Warren
Department of Comparative Medicine, School of Medicine, University of Washington, Seattle WA.
Department of Bioengineering, College of Engineering and School of Medicine, University of Washington, Seattle WA.
bioRxiv. 2023 Nov 17:2023.11.16.567423. doi: 10.1101/2023.11.16.567423.
Brain aging and cognitive decline are aspects of growing old. Age-related cognitive impairment entails the early stages of cognitive decline, and is extremely common, affecting millions of older people. Investigation into early cognitive decline as a treatable condition is relevant to a wide range of cognitive impairment conditions, since mild age-related neuropathology increases risk for more severe neuropathology and dementia associated with Alzheimer's Disease. Recent studies suggest that the naturally occurring peptide GHK (glycyl-L-histidyl-L-lysine) in its Cu-bound form, has the potential to treat cognitive decline associated with aging. In order to test this concept, male and female C57BL/6 mice, 20 months of age, were given intranasal GHK-Cu, 15 mg/kg daily, for two months. Results showed that mice treated with intranasal GHK-Cu had an enhanced level of cognitive performance in spatial memory and learning navigation tasks, and expressed decreased neuroinflammatory and axonal damage markers compared to mice treated with intranasal saline. These observations suggest that GHK-Cu can enhance resilience to brain aging, and has translational implications for further testing in both preclinical and clinical studies using an atomizer device for intranasal delivery.
脑衰老和认知衰退是衰老过程中的一部分。与年龄相关的认知障碍涉及认知衰退的早期阶段，极为常见，影响着数百万老年人。将早期认知衰退作为一种可治疗的病症进行研究，与广泛的认知障碍病症相关，因为轻度的与年龄相关的神经病理学增加了患更严重神经病理学以及与阿尔茨海默病相关的痴呆症的风险。最近的研究表明，天然存在的肽GHK（甘氨酰-L-组氨酰-L-赖氨酸）的铜结合形式有潜力治疗与衰老相关的认知衰退。为了验证这一概念，对20月龄的雄性和雌性C57BL/6小鼠每日经鼻给予15mg/kg的GHK-Cu，持续两个月。结果显示，与经鼻给予生理盐水的小鼠相比，经鼻给予GHK-Cu治疗的小鼠在空间记忆和学习导航任务中的认知表现水平有所提高，并且神经炎症和轴突损伤标志物表达降低。这些观察结果表明，GHK-Cu可以增强对脑衰老的抵抗力，并且对于使用雾化器装置经鼻给药在临床前和临床研究中进行进一步测试具有转化意义。
