QBI Neuroscience Seminar: Investigations of the effects of scanning focused ultrasound in mouse models of Alzheimer’s disease
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- Gerhard Leinenga
Queensland Brain Institute, University of Queensland
Title: Investigations of the effects of scanning focused ultrasound in mouse models of Alzheimer’s disease
Abstract: Focused ultrasound, in combination with injected microbubbles has been used to disrupt the blood-brain-barrier and allow delivery of drugs to the brain. We have developed a protocol to temporarily open the blood-brain barrier throughout the entire brain of the mouse by using a scanning approach and short sonications at each spot, combined with intravenous injection of microbubbles. We treated amyloid-beta–depositing APP23 mice with repeated scanning ultrasound (SUS) treatments of the brain to remove amyloid-beta, without the need for any additional therapeutic agent such as anti-amyloid-beta antibody. Treated APP23 mice showed reduced soluble amyloid-beta levels and reduced plaque burden, concomitant with microglial activation, in the absence of neuronal damage or astrogliosis. In tau models of Alzheimer’s disease, SUS was able to facilitate the delivery of tau-targeted therapeutics to neurons and reduce tau hyperphosphorylation in pR5 tau transgenic mice. To determine whether SUS treatment has any acute or long-term adverse effects the effect of SUS on the morphology and electrophysiological properties of CA1 pyramidal neurons in wild-type mice was also studied. The electrophysiological properties of neurons were normal after single and repeated treatments and repeated treatments prevented the decrease in dendritic branch length and complexity seen in sham-treated mice. The first steps we are taking to translate the technique to large animals and eventually humans will also be discussed.
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