Long-lasting restoration of memory function and hippocampal synaptic plasticity by focused ultrasound in Alzheimer's disease

被引：15

作者：

Kong, Chanho ^{[1
]}

Ahn, Ji Woong ^{[2
]}

Kim, Sohyun ^{[2
]}

Park, Ji Young ^{[1
]}

Na, Young Cheol ^{[3
]}

Chang, Jin Woo ^{[1
]}

Chung, Seungsoo ^{[2
,5
]}

Chang, Won Seok ^{[1
,4
]}

机构：

[1] Yonsei Univ, Dept Neurosurg, Coll Med, Seoul, South Korea

[2] Yonsei Univ, Dept Physiol, Coll Med, Seoul, South Korea

[3] Catholic Kwandong Univ, Int St Marys Hosp, Dept Neurosurg, Coll Med, Incheon, South Korea

[4] Yonsei Univ, Dept Neurosurg, Coll Med, 50 Yonsei Ro, Seoul, South Korea

[5] Yonsei Univ, Dept Physiol, Coll Med, 50 Yonsei Ro, Seoul, South Korea

来源：

BRAIN STIMULATION | 2023年 / 16卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

Focused ultrasound; Long-term potentiation; Blood -brain barrier; Alzheimer's disease; Cognitive function; BLOOD-BRAIN-BARRIER; TERM POTENTIATION; ADULT NEUROGENESIS; PLAQUE REDUCTION; TAU; DELIVERY;

D O I：

10.1016/j.brs.2023.05.014

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Background: Focused ultrasound (FUS) is a medical technology that non-invasively stimulates the brain and has been applied in thermal ablation, blood-brain barrier (BBB) opening, and neuromodulation. In recent years, numerous experiences and indications for the use of FUS in clinical and preclinical studies have rapidly expanded. Focused ultrasound-mediated BBB opening induces cognitive enhancement and neurogenesis; how-ever, the underlying mechanisms have not been elucidated.Methods: Here, we investigate the effects of FUS-mediated BBB opening on hippocampal long-term potentiation (LTP) and cognitive function in a 5xFAD mouse model of Alzheimer's disease (AD). We applied FUS with microbubble to the hippocampus and LTP was measured 6 weeks after BBB opening using FUS. Field recordings were made with a concentric bipolar electrode positioned in the CA1 region using an extracellular glass pipette filled with artificial cerebrospinal fluid. Morris water maze and Y-maze was performed to test cognitive function.Results: Our results demonstrated that FUS-mediated BBB opening has a significant impact on increasing LTP at Schaffer collateral -CA1 synapses and rescues cognitive dysfunction and working memory. These effects per-sisted for up to 7 weeks post-treatment. Also, FUS-mediated BBB opening in the hippocampus increased PKA phosphorylation.Conclusion: Therefore, it could be a promising treatment for neurodegenerative diseases as it remarkably in-creases LTP, thereby improving working memory.

引用

页码：857 / 866

页数：10

共 44 条

[1] Amyloid Plaque Reduction With Antibodies Crossing the Blood-Brain Barrier, Which Was Opened in 3 Sessions of Focused Ultrasound in a Rabbit Model [J].