Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer's Disease-Like Experimental Mouse Model.
Authors: Luo K, Wang Y, Chen WS, Feng X, Liao Y, Chen S, Liu Y, Liao C, Chen M, Ao L
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 A<i>β</i> <sub>1-42</sub>. 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 A<i>β</i>, 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.
Introduction
Purpose
Drug delivery with BBB opening
Study Objective
To evaluate whether focused ultrasound–mediated blood–brain barrier opening combined with gastrodin administration can alleviate memory deficits and neuropathology in an Aβ1-42–induced Alzheimer's disease mouse model.
Animal model / Human subject
Mouse (Mus musculus); strain not reported; age not reported; sex not reported
Disease model
Alzheimer's disease
Targeted brain region(s)
Hippocampus
Cargo name and characteristics
Gastrodin (GAS): a phenolic glycoside small molecule extracted from the herb Gastrodia elata, used as the therapeutic agent; Amyloid beta 1-42 (Aβ1-42): aggregation-prone peptide (protein) used experimentally to induce an AD-like model via unilateral intracerebroventricular (ICV) injection.
Outcomes and Safety
Summary of Outcomes
Combined focused ultrasound (FUS)-mediated BBB opening with gastrodin (FUS+GAS), but not GAS or FUS alone, alleviated memory deficits (increased novel-arm time in the Y-maze), enhanced waste-clearance, reduced hippocampal Aβ, tau and p-tau levels, and upregulated BDNF, synaptophysin and PSD-95 in an Aβ1-42 mouse model.
Duration of biological effect
15 days
Safety-related matter
The paper does not report any safety issues or adverse effects. No adverse events associated with gastrodin, FUS, or their combination were mentioned in the AD-like mouse model.
Brain Region
Ultrasound Parameters
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
Multiple sessions
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