{"title":"Investigation of protective effects of olanzapine on impaired learning and memory using behavioral tests in a rat model of Alzheimer's disease.","authors":"Somayeh Komaki, Parsa Amiri, Samaneh Safari, Ebrahim Abbasi, Fatemeh Ramezani-Aliakbari, Mandana Golipoor, Masoumeh Kourosh-Arami, Masome Rashno, Alireza Komaki","doi":"10.3389/fnagi.2025.1376074","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>Rats were randomly assigned to one of five groups (<i>n</i> = 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 <i>via</i> gavage for two months, and an AD + OLZ group that received OLZ for one month before and one month after AD induction.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":12450,"journal":{"name":"Frontiers in Aging Neuroscience","volume":"17 ","pages":"1376074"},"PeriodicalIF":4.1000,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11865076/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Aging Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnagi.2025.1376074","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.