Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents

Chemotherapy-related cognitive impairment (CRCI), is a well-recognized phenomenon in cancer patients who have undergone chemotherapy but the exact molecular mechanisms underpinning CRCI remain elusive. Symptoms reported by people with CRCI resemble those experienced by people with age-related neurod...

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Main Authors: Mohammad-Sajad Zare, Navid Abedpoor, Fatemeh Hajibabaie, Adam K. Walker
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996125001603
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author Mohammad-Sajad Zare
Navid Abedpoor
Fatemeh Hajibabaie
Adam K. Walker
author_facet Mohammad-Sajad Zare
Navid Abedpoor
Fatemeh Hajibabaie
Adam K. Walker
author_sort Mohammad-Sajad Zare
collection DOAJ
description Chemotherapy-related cognitive impairment (CRCI), is a well-recognized phenomenon in cancer patients who have undergone chemotherapy but the exact molecular mechanisms underpinning CRCI remain elusive. Symptoms reported by people with CRCI resemble those experienced by people with age-related neurodegenerative disorders (ARNDDs), yet no clear connection between CRCI and ARNDDs has been reported to date. The existence of shared mechanisms between these conditions offers opportunities for repurposing drugs already approved for the treatment of ARNDDs to improve symptoms of CRCI. Given that there is no available microarray or RNA-Seq data from the brains of people who have experienced CRCI, we investigated to what extent brain gene expression perturbations from validated rodent models of CRCI induced by chemotherapy compared with validated rodent models of Alzheimer’s disease and Parkinson’s disease. We utilized multiple bioinformatic analyses, including functional enrichment, protein-protein interaction network analyses, gene ontology analyses and identification of hub genes to reveal connections between comparable gene expression perturbations observed in these conditions. Collectively 165 genes overlapped between CRCI and Parkinson’s disease and/or Alzheimer’s disease, and 15 overlapped between all three conditions. The joint genes between Alzheimer’s disease, Parkinson’s disease and CRCI demonstrate an average of 83.65% nucleotide sequence similarity to human orthologues. Gene ontology and pathway enrichment analyses suggest mechanisms involved in neural activity and inflammatory response as the key components of the studied neuropathological conditions. Accordingly, genes in which expression was comparably affected in all three condition models could be attributed to neuroinflammation, cell cycle arrest, and changes in physiological neural activity.
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spelling doaj-art-7c951e4448434f8d813fbe0f30f577212025-08-20T01:50:30ZengElsevierNeurobiology of Disease1095-953X2025-07-0121110694410.1016/j.nbd.2025.106944Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodentsMohammad-Sajad Zare0Navid Abedpoor1Fatemeh Hajibabaie2Adam K. Walker3Department of Chemistry, University of Georgia, Athens, GA, 30602, USA; Iranian Cancer Control Center (MACSA), Isfahan, Iran; Corresponding author at: Research and Education Unit, Iranian Cancer Control Center, No. 29 Amin-o-Doleh Blind-Alley, 35th Alley, Motahari St., Isfahan, Iran.Department of Sports Physiology, Isf.C., Islamic Azad University, Isfahan, IranDepartment of Biology, ShK.C., Islamic Azad University, Shahrekord, IranDiscipline of Psychiatry and Mental Health, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.; Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, Randwick 2031, NSW, Australia.; Corresponding author at: Laboratory of ImmunoPsychiatry, Neuroscience Research Australia, 139 Barker Street, Randwick 2031, NSW, Australia.Chemotherapy-related cognitive impairment (CRCI), is a well-recognized phenomenon in cancer patients who have undergone chemotherapy but the exact molecular mechanisms underpinning CRCI remain elusive. Symptoms reported by people with CRCI resemble those experienced by people with age-related neurodegenerative disorders (ARNDDs), yet no clear connection between CRCI and ARNDDs has been reported to date. The existence of shared mechanisms between these conditions offers opportunities for repurposing drugs already approved for the treatment of ARNDDs to improve symptoms of CRCI. Given that there is no available microarray or RNA-Seq data from the brains of people who have experienced CRCI, we investigated to what extent brain gene expression perturbations from validated rodent models of CRCI induced by chemotherapy compared with validated rodent models of Alzheimer’s disease and Parkinson’s disease. We utilized multiple bioinformatic analyses, including functional enrichment, protein-protein interaction network analyses, gene ontology analyses and identification of hub genes to reveal connections between comparable gene expression perturbations observed in these conditions. Collectively 165 genes overlapped between CRCI and Parkinson’s disease and/or Alzheimer’s disease, and 15 overlapped between all three conditions. The joint genes between Alzheimer’s disease, Parkinson’s disease and CRCI demonstrate an average of 83.65% nucleotide sequence similarity to human orthologues. Gene ontology and pathway enrichment analyses suggest mechanisms involved in neural activity and inflammatory response as the key components of the studied neuropathological conditions. Accordingly, genes in which expression was comparably affected in all three condition models could be attributed to neuroinflammation, cell cycle arrest, and changes in physiological neural activity.http://www.sciencedirect.com/science/article/pii/S0969996125001603Cancer-related cognitive impairmentNeuroinflammationParkinson’s diseaseAlzheimer’s diseaseSynaptic transmissionNeuroprotection
spellingShingle Mohammad-Sajad Zare
Navid Abedpoor
Fatemeh Hajibabaie
Adam K. Walker
Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
Neurobiology of Disease
Cancer-related cognitive impairment
Neuroinflammation
Parkinson’s disease
Alzheimer’s disease
Synaptic transmission
Neuroprotection
title Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
title_full Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
title_fullStr Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
title_full_unstemmed Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
title_short Gene co-expression patterns shared between chemobrain and neurodegenerative disease models in rodents
title_sort gene co expression patterns shared between chemobrain and neurodegenerative disease models in rodents
topic Cancer-related cognitive impairment
Neuroinflammation
Parkinson’s disease
Alzheimer’s disease
Synaptic transmission
Neuroprotection
url http://www.sciencedirect.com/science/article/pii/S0969996125001603
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