Investigation of protective effects of olanzapine on impaired learning and memory using behavioral tests in a rat model of Alzheimer's disease.

IF 4.5 2区 医学 Q2 GERIATRICS & GERONTOLOGY Frontiers in Aging Neuroscience Pub Date : 2025-02-13 eCollection Date: 2025-01-01 DOI:10.3389/fnagi.2025.1376074
Somayeh Komaki, Parsa Amiri, Samaneh Safari, Ebrahim Abbasi, Fatemeh Ramezani-Aliakbari, Mandana Golipoor, Masoumeh Kourosh-Arami, Masome Rashno, Alireza Komaki
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Abstract

Introduction: Evidence suggests that oxidative stress plays a critical role in the pathogenesis and progression of Alzheimer's disease (AD). Consequently, antioxidants may mitigate neurotoxicity induced by beta-amyloid (Aβ) and potentially reduce cell death. Previous research has demonstrated that olanzapine (OLZ) possesses antioxidant and neuroprotective properties. In this study, we investigated the protective and therapeutic effects of OLZ on an animal model of AD induced by Aβ using behavioral assessments.

Methods: Rats were randomly assigned to one of five groups (n = 10 rats per group): a control group, a sham group that received an intracerebrovascular (ICV) injection of phosphate-buffered saline (the solvent for Aβ), an AD group that received an ICV injection of Aβ, an OLZ group that received OLZ via gavage for two months, and an AD + OLZ group that received OLZ for one month before and one month after AD induction.

Results: We used the Elevated Plus Maze (EPM), Novel Object Recognition Test (NORT), Barnes Maze (BM), Passive Avoidance Test (PAT), and Morris Water Maze (MWM) to assess behavioral performance in the experimental rats. Aβ administration impaired cognition and increased anxiety-like behavior. Treatment with OLZ improved cognitive decline and reduced anxiety-like behavior in Aβ-infused rats.

Conclusion: Our findings suggest that OLZ can restore cognitive performance and alleviate anxiety-like behavior following Aβ injection. Thus, OLZ may have both preventive and therapeutic potential for AD and could be considered a viable pharmacological option.

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使用阿尔茨海默病大鼠模型的行为测试研究奥氮平对受损学习和记忆的保护作用。
有证据表明,氧化应激在阿尔茨海默病(AD)的发病和进展中起着关键作用。因此,抗氧化剂可以减轻β -淀粉样蛋白(Aβ)引起的神经毒性,并可能减少细胞死亡。先前的研究表明奥氮平(OLZ)具有抗氧化和神经保护作用。本研究采用行为学评价的方法研究了OLZ对Aβ诱导的AD动物模型的保护作用和治疗作用。方法:将大鼠随机分为5组(每组10只):对照组、假手术组(ICV)脑内注射磷酸缓冲盐水(制备a β的溶剂)、AD组(ICV注射a β)、OLZ组(灌胃OLZ 2个月)、AD + OLZ组(诱导AD前1个月、诱导AD后1个月)。结果:采用高架+迷宫(EPM)、新物体识别测试(NORT)、巴恩斯迷宫(BM)、被动回避测试(PAT)和莫里斯水迷宫(MWM)对实验大鼠的行为表现进行评估。Aβ给药会损害认知能力,增加焦虑样行为。OLZ治疗改善了a β注入大鼠的认知能力下降并减少了焦虑样行为。结论:OLZ可恢复Aβ注射后的认知能力,减轻焦虑样行为。因此,OLZ可能具有预防和治疗AD的潜力,可以被认为是一种可行的药理学选择。
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来源期刊
Frontiers in Aging Neuroscience
Frontiers in Aging Neuroscience GERIATRICS & GERONTOLOGY-NEUROSCIENCES
CiteScore
6.30
自引率
8.30%
发文量
1426
期刊介绍: Frontiers in Aging Neuroscience is a leading journal in its field, publishing rigorously peer-reviewed research that advances our understanding of the mechanisms of Central Nervous System aging and age-related neural diseases. Specialty Chief Editor Thomas Wisniewski at the New York University School of Medicine is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
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