Lv Shiya, Mo Fan, Xu Zhaojie, Wang Yu, Liu Yaoyao, Han Meiqi, Duan Yiming, Jing Luyi, Kong Fanli, Jia Qianli, Li Ming, Xu Wei, Jiao Peiyao, Wang Mixia, Liu Juntao, Luo Jinping, Wang Junbo, Fan Zhongwei, Song Yilin, Wu Yirong, Cai Xinxia
State Key Laboratory of Transducer Technology, Aerospace Information Research Institute, Chinese Academy of Sciences, Beijing, 100190, China.
University of Chinese Academy of Sciences, Beijing, 100049, China.
Nat Commun. 2025 Jul 1;16(1):5948. doi: 10.1038/s41467-025-60903-1.
Hippocampal degeneration and reduced dopamine levels in Alzheimer's disease are associated with severe memory and cognitive impairments. However, the lack of multifunctional in situ neural chips has posed challenges for integrated investigations of Alzheimer's disease pathophysiology, dopamine dynamics, and neural activity. Therefore, we developed NeuroRevive-FlexChip, a flexible neural interface capable of precise electrical modulation and simultaneous in situ monitoring of dopamine levels and neural activity. In this study, the NeuroRevive-FlexChip demonstrates improved electrochemical detection sensitivity and modulation efficiency. Preliminary observations in APP/PS1 mice indicate that implantation of the chip in the hippocampal CA1 region, combined with 40 Hz stimulation, may contribute to the restoration of dopamine release, a reduction in neuronal hyper-synchronization, and a shift toward more stable firing patterns. These effects appear to be modulated by dopamine-related mechanisms. Furthemore, 40 Hz stimulation was observed to correlate with reduction in Aβ deposition and modest improvements in spatial cognition performance, as assessed by the Y-maze test. These findings highlight the potential of NeuroRevive-FlexChip as a research tool for investigating the mechanisms of 40 Hz stimulation in Alzheimer's disease models. Further studies could explore its utility in clarifying the relationship between dopamine dysfunction, neural activity, and amyloid pathology. While these early results are promising, additional preclinical and translational research will be necessary to assess the therapeutic potential of this approach for neurodegenerative diseases.
阿尔茨海默病中的海马体退化和多巴胺水平降低与严重的记忆和认知障碍有关。然而,缺乏多功能原位神经芯片给阿尔茨海默病病理生理学、多巴胺动力学和神经活动的综合研究带来了挑战。因此,我们开发了NeuroRevive-FlexChip,一种能够精确电调制并同时原位监测多巴胺水平和神经活动的柔性神经接口。在本研究中,NeuroRevive-FlexChip展示了更高的电化学检测灵敏度和调制效率。在APP/PS1小鼠中的初步观察表明,将芯片植入海马体CA1区并结合40Hz刺激,可能有助于恢复多巴胺释放、减少神经元过度同步,并向更稳定的放电模式转变。这些效应似乎受多巴胺相关机制调节。此外,通过Y迷宫试验评估,观察到40Hz刺激与Aβ沉积减少以及空间认知性能的适度改善相关。这些发现突出了NeuroRevive-FlexChip作为研究阿尔茨海默病模型中40Hz刺激机制的研究工具的潜力。进一步的研究可以探索其在阐明多巴胺功能障碍、神经活动和淀粉样蛋白病理之间关系方面的效用。虽然这些早期结果很有前景,但还需要额外的临床前和转化研究来评估这种方法对神经退行性疾病的治疗潜力。
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