Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-Like Experimental Mouse Model

• Published in: Journal of neural transplantation & plasticity Vol. 2022; pp. 1 - 13
• Main Authors: Luo, Kaixuan, Wang, Yuhong, Chen, Wen-Shiang, Feng, Xiangjun, Liao, Yehui, Chen, Shaochun, Liu, Yao, Liao, Chengde, Chen, Moxian, Ao, Lijuan
• Format: Journal Article
• Language: English
• Published: United States Hindawi 13.01.2022; John Wiley & Sons, Inc; Wiley
• Subjects: Advertising executives; Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer Disease - therapy; Alzheimer's disease; Analysis; Animals; Apoptosis; Benzyl Alcohols - pharmacology; Benzyl Alcohols - therapeutic use; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - pathology; Brain; Brain - drug effects; Brain - pathology; Cavitation; Combined Modality Therapy; Dementia; Disease Models, Animal; FDA approval; Glucosides - pharmacology; Glucosides - therapeutic use; Health aspects; Kinases; Laboratory animals; Maze Learning - drug effects; Memory; Memory Disorders - drug therapy; Memory Disorders - pathology; Memory Disorders - therapy; Mice; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Pathology; Peptides; Permeability; Ultrasonic imaging; Ultrasonography, Interventional - methods; China
• ISSN: 2090-5904; 0792-8483; 1687-5443; 1687-5443
• DOI: 10.1155/2022/5241449

Alzheimer’s disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb—Gastrodia elata—and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aβ1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aβ, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.