Administration of Aripiprazole Alleviates Memory Impairment and Restores Damaged Glutamatergic System in 5xFAD Mice.

IF 3 4区 医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING Molecular Imaging and Biology Pub Date : 2024-10-01 Epub Date: 2024-08-22 DOI:10.1007/s11307-024-01944-8
Hae-June Lee, Hyun-Yong Kim, Se Jong Oh, Yeonghoon Son, Kyung Jun Kang, Kyung Rok Nam, Jae Yong Choi
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Abstract

Purpose: Many patients with Alzheimer's disease (AD) also have psychosis, and it has been reported that these patients have more severely impaired cognitive functions than patients without psychosis. The glutamatergic system in the brain is known to play an important role in memory and learning in the neural circuits. However, there has been limited research on how antipsychotic drugs affect the glutamatergic system of AD. Therefore, we aimed to investigate the effects of aripiprazole on the glutamatergic system in an animal model of AD using functional molecular imaging.

Procedures: In this study, 5xFAD mice were used as the animal model. At the age of 5 months, the mice were divided into wild-type, vehicle control, and aripiprazole-treated groups (n = 6 per group). The aripiprazole-treated group was administered aripiprazole for 2 months at a dose of 1 mg·kg-1·day-1. At 7 months of age, the animals underwent behavioral tests and glutamate positron emission tomography (PET) scans.

Results: The aripiprazole-treated group exhibited alleviated memory impairment in a novel object recognition test. Moreover, this group displayed 7-8% higher binding in the glutamate PET scan than the vehicle-treated 5xFAD group. Postmortem examination confirmed the recovery of glutamatergic damage.

Conclusions: The administration of aripiprazole alleviated memory impairment and restored the damaged glutamatergic system in 5xFAD mice. Although the use of aripiprazole in AD patients may be a constraint in terms of safety, we confirmed the possibility that the administration of antipsychotic drugs can be effective in AD.

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阿立哌唑能缓解 5xFAD 小鼠的记忆损伤并恢复受损的谷氨酸能系统
目的:许多阿尔茨海默病(AD)患者同时患有精神病,据报道,这些患者的认知功能受损程度比没有精神病的患者更严重。众所周知,大脑中的谷氨酸能系统在神经回路的记忆和学习中发挥着重要作用。然而,关于抗精神病药物如何影响 AD 的谷氨酸能系统的研究还很有限。因此,我们旨在利用功能分子成像技术研究阿立哌唑对AD动物模型中谷氨酸能系统的影响:本研究使用 5xFAD 小鼠作为动物模型。在小鼠5个月大时,将其分为野生型组、药物对照组和阿立哌唑治疗组(每组6只)。阿立哌唑治疗组的阿立哌唑剂量为1毫克-千克-1-天-1,为期2个月。在动物7个月大时,对其进行行为测试和谷氨酸正电子发射断层扫描(PET):结果:阿立哌唑治疗组在新物体识别测试中的记忆障碍有所缓解。此外,在谷氨酸正电子发射计算机断层扫描中,阿立哌唑治疗组的结合率比车辆治疗的 5xFAD 组高 7-8%。尸检证实了谷氨酸能损伤的恢复:结论:阿立哌唑能缓解 5xFAD 小鼠的记忆损伤,并恢复受损的谷氨酸能系统。虽然阿立哌唑在AD患者中的使用可能会受到安全性方面的限制,但我们证实了服用抗精神病药物对AD有效的可能性。
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来源期刊
CiteScore
6.90
自引率
3.20%
发文量
95
审稿时长
3 months
期刊介绍: Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.
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