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

ABSTRACT: 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 Aβ _1-42. 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.

SUBMITTER: Luo K

PROVIDER: S-EPMC8776436 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Long-term episodic memory deficits in Alzheimer's disease (AD) are well characterised but, until recently, short-term memory (STM) function has attracted far less attention. We employed a recently-developed, delayed reproduction task which requires participants to reproduce precisely the remembered location of items they had seen only seconds previously. This paradigm provides not only a continuous measure of localization error in memory, but also an index of relational binding by determining the frequency with which an object is misplaced to the location of one of the other items held in memory. Such binding errors in STM have previously been found on this task to be sensitive to medial temporal lobe (MTL) damage in focal lesion cases. Twenty individuals with pathological mutations in presenilin 1 or amyloid precursor protein genes for familial Alzheimer's disease (FAD) were tested together with 62 healthy controls. Participants were assessed using the delayed reproduction memory task, a standard neuropsychological battery and structural MRI. Overall, FAD mutation carriers were worse than controls for object identity as well as in gross localization memory performance. Moreover, they showed greater misbinding of object identity and location than healthy controls. Thus they would often mislocalize a correctly-identified item to the location of one of the other items held in memory. Significantly, asymptomatic gene carriers - who performed similarly to healthy controls on standard neuropsychological tests - had a specific impairment in object-location binding, despite intact memory for object identity and location. Consistent with the hypothesis that the hippocampus is critically involved in relational binding regardless of memory duration, decreased hippocampal volume across FAD participants was significantly associated with deficits in object-location binding but not with recall precision for object identity or localization. Object-location binding may therefore provide a sensitive cognitive biomarker for MTL dysfunction in a range of diseases including AD.

Dataset Information

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

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