Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model

Cognitive impairment and anxiety are common side effects of chemotherapy, particularly with the use of doxorubicin (DOX), known as “chemobrain”. This study aimed to examine the dose-dependent effects of DOX on cognitive decline, anxiety, and locomotor activity in healthy female Wistar rats. The rats...

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Main Authors: Ângela Amaro-Leal, Ana I. Afonso, Filipa Machado, Liana Shvachiy, Isabel Rocha, Tiago F. Outeiro, Vera Geraldes
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/13/11/939
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author Ângela Amaro-Leal
Ana I. Afonso
Filipa Machado
Liana Shvachiy
Isabel Rocha
Tiago F. Outeiro
Vera Geraldes
author_facet Ângela Amaro-Leal
Ana I. Afonso
Filipa Machado
Liana Shvachiy
Isabel Rocha
Tiago F. Outeiro
Vera Geraldes
author_sort Ângela Amaro-Leal
collection DOAJ
description Cognitive impairment and anxiety are common side effects of chemotherapy, particularly with the use of doxorubicin (DOX), known as “chemobrain”. This study aimed to examine the dose-dependent effects of DOX on cognitive decline, anxiety, and locomotor activity in healthy female Wistar rats. The rats were divided into groups receiving low (2 mg/kg), intermediate (4 mg/kg), and high (5 mg/kg) doses of DOX for four weeks, alongside a control group. Behavioral tests, including open field, elevated plus maze, and Y-maze tests, assessed anxiety, locomotion, and cognitive performance, while brain tissue analysis evaluated neuroinflammation using markers such as GFAP and Iba-1. The results showed that all doses of DOX induced anxiety-like behavior, reduced locomotion, and caused neuroinflammation in the hippocampus, with more severe effects at higher doses. Notably, high-dose DOX also caused short-term memory deficits. These findings highlight the dose-dependent nature of DOX’s impact on behavior and cognition, suggesting that DOX plays a key role in the development of cognitive symptoms during chemotherapy. Further research is needed to understand the mechanisms behind these effects and to explore potential interventions.
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publishDate 2024-11-01
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spelling doaj-art-e041f1ae605c4b1e9ffd4f8121f5c13f2024-11-26T17:52:32ZengMDPI AGBiology2079-77372024-11-01131193910.3390/biology13110939Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal ModelÂngela Amaro-Leal0Ana I. Afonso1Filipa Machado2Liana Shvachiy3Isabel Rocha4Tiago F. Outeiro5Vera Geraldes6Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, 2829-511 Almada, PortugalFaculdade de Medicina, Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, PortugalFaculdade de Medicina, Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, PortugalCentro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina, Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, PortugalFaculdade de Medicina, Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, PortugalDepartment of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, 37073 Göttingen, GermanyFaculdade de Medicina, Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, PortugalCognitive impairment and anxiety are common side effects of chemotherapy, particularly with the use of doxorubicin (DOX), known as “chemobrain”. This study aimed to examine the dose-dependent effects of DOX on cognitive decline, anxiety, and locomotor activity in healthy female Wistar rats. The rats were divided into groups receiving low (2 mg/kg), intermediate (4 mg/kg), and high (5 mg/kg) doses of DOX for four weeks, alongside a control group. Behavioral tests, including open field, elevated plus maze, and Y-maze tests, assessed anxiety, locomotion, and cognitive performance, while brain tissue analysis evaluated neuroinflammation using markers such as GFAP and Iba-1. The results showed that all doses of DOX induced anxiety-like behavior, reduced locomotion, and caused neuroinflammation in the hippocampus, with more severe effects at higher doses. Notably, high-dose DOX also caused short-term memory deficits. These findings highlight the dose-dependent nature of DOX’s impact on behavior and cognition, suggesting that DOX plays a key role in the development of cognitive symptoms during chemotherapy. Further research is needed to understand the mechanisms behind these effects and to explore potential interventions.https://www.mdpi.com/2079-7737/13/11/939doxorubicinanxietychemotherapy-induced cognitive impairmentcognitive dysfunction
spellingShingle Ângela Amaro-Leal
Ana I. Afonso
Filipa Machado
Liana Shvachiy
Isabel Rocha
Tiago F. Outeiro
Vera Geraldes
Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model
Biology
doxorubicin
anxiety
chemotherapy-induced cognitive impairment
cognitive dysfunction
title Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model
title_full Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model
title_fullStr Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model
title_full_unstemmed Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model
title_short Dose-Dependent Cognitive Decline, Anxiety, and Locomotor Impairments Induced by Doxorubicin: Evidence from an Animal Model
title_sort dose dependent cognitive decline anxiety and locomotor impairments induced by doxorubicin evidence from an animal model
topic doxorubicin
anxiety
chemotherapy-induced cognitive impairment
cognitive dysfunction
url https://www.mdpi.com/2079-7737/13/11/939
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