Theranexus, Lyon, France.
Lyon Neuroscience Research Center, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR5292, INSERM U1028, Lyon, France.
J Psychopharmacol. 2022 Nov;36(11):1273-1279. doi: 10.1177/02698811221128963. Epub 2022 Oct 7.
There is an urgent need to understand and reverse cognitive impairment. The lack of appropriate animal models combined with the limited knowledge of pathophysiological mechanisms makes the development of new cognition-enhancing drugs complex. Scopolamine is a pharmacologic agent which impairs cognition and functional imaging in a wide range of animal species, similarly to what is seen in cognitive impairment in humans.
In this study, using a functional ultrasound (fUS) neuroimaging technique, we monitored the impact of donepezil (DPZ), a potent acetylcholinesterase inhibitor and first-line treatment in patients with mild to moderate Alzheimer's disease, in a scopolamine-induced mouse model.
We demonstrated that despite its low impact on the cerebral blood volume (CBV) signal, scopolamine injection produced an overall decrease in functional connectivity between various brain areas. In addition, we revealed that DPZ induced a strong decrease in CBV signal without causing a difference in functional connectivity.
Finally, our work highlighted that DPZ counteracted the impact of scopolamine on functional connectivity changes and confirmed the interest of using pharmaco-fUS imaging on cognitive disorders, both in frequent and rare neurological disorders.
迫切需要了解和逆转认知障碍。缺乏适当的动物模型以及对病理生理机制的了解有限，使得新的认知增强药物的开发变得复杂。东莨菪碱是一种药理学药物，可在多种动物物种中损害认知和功能成像，类似于人类认知障碍。
在这项研究中，我们使用功能超声（fUS）神经影像学技术，监测了多奈哌齐（DPZ）在东莨菪碱诱导的小鼠模型中的影响，DPZ 是一种强效乙酰胆碱酯酶抑制剂，也是轻度至中度阿尔茨海默病患者的一线治疗药物。
我们表明，尽管东莨菪碱对脑血容量（CBV）信号的影响不大，但注射东莨菪碱会导致大脑各个区域之间的功能连接整体下降。此外，我们还发现 DPZ 会强烈降低 CBV 信号，而不会导致功能连接的差异。
最后，我们的工作强调了 DPZ 可拮抗东莨菪碱对功能连接变化的影响，并证实了在认知障碍中使用药物 fUS 成像的重要性，包括在常见和罕见的神经障碍中。
