ArticleBehavioural brain research2015
Doxorubicin and cyclophosphamide induce cognitive dysfunction and activate the ERK and AKT signaling pathways.
Article in Behavioural brain research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- Cytokines and Brain-Derived Neurotrophic Factor as Biomarkers of Cognitive Impairment Related to Breast Cancer and Its Treatments: A Systematic Review.International journal of molecular sciences · 2025Pooled it
- A systematic review of the neurobiological mechanisms of chemotherapy-induced deficits in executive functions.Brain, behavior, & immunity - health · 2026Review
- Roles of MAPKs, Including Those Activated by BDNF/TrkB, and Their Contribution in Neurodegenerative Diseases.International journal of molecular sciences · 2026Review
- Dapagliflozin Ameliorates Doxorubicin-Induced Chemobrain and Cognitive Abnormalities in Rats: Modulation of AKT/GSK-3β and Wnt/β-Catenin Pathways.Neurochemical research · 2025Article
- Chemotherapy treatment alters DNA methylation patterns in the prefrontal cortex of female rat brain.Scientific reports · 2025Article
- Association of phosphorylation status of ERK and genetic MAPK alterations in pediatric tumors.Scientific reports · 2025Article
- Effects of empagliflozin on cyclophosphamide-induced neurotoxicity in rats without diabetes.Turkish journal of medical sciences · 2025Article
- Coenzyme Q10 ameliorates chemotherapy-induced cognitive impairment in mice: a preclinical study.Molecular biology reports · 2024Article
- In-vitro and in-vivo studies of two-drug cocktail therapy targeting chemobrain via the Nrf2/NF-κB signaling pathway.Journal of molecular histology · 2024Article
- Wnt3a/GSK3β/β-catenin Signalling Modulates Doxorubicin-associated Memory Deficits in Breast Cancer.Molecular neurobiology · 2024Article
- The impact of APOE and smoking history on cognitive function in older, long-term breast cancer survivors.Journal of cancer survivorship : research and practice · 2024Article
- Article
- Cancer related cognitive impairment: a downside of cancer treatment.Frontiers in oncology · 2024Review
- Fertility Protection, A Novel Concept: Umbilical Cord Mesenchymal Stem Cell-Derived Exosomes Protect against Chemotherapy-Induced Testicular Cytotoxicity.International journal of molecular sciences · 2023Article
- L-carnitine Modulates Cognitive Impairment Induced by Doxorubicin and Cyclophosphamide in Rats; Insights to Oxidative Stress, Inflammation, Synaptic Plasticity, Liver/brain, and Kidney/brain Axes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Role of chemotherapeutic drugs in immunomodulation of cancer.Current research in immunology · 2023Review
- Phenyl-2-aminoethyl selenide ameliorates hippocampal long-term potentiation and cognitive deficits following doxorubicin treatment.PloS one · 2023Article
- Piracetam as a Therapeutic Agent for Doxorubicin-Induced Cognitive Deficits by Enhancing Cholinergic Functions and Reducing Neuronal Inflammation, Apoptosis, and Oxidative Stress in Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Role of inflammation and oxidative stress in chemotherapy-induced neurotoxicity.Immunologic research · 2022Review
- TRPC6 N338S is a gain-of-function mutant identified in patient with doxorubicin-induced cardiotoxicity.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Chemotherapy is associated with long-term cognitive deficits in breast cancer survivors. Studies suggest that these impairments result in the loss of cognitive reserve and/or induce a premature aging of the brain. This study has been aimed to determine the potential underlying mechanisms that induce cognitive impairments by chemotherapeutic agents commonly used in breast cancer. Intact and ovariectomized (OVX) female rats were treated intravenously with either saline or a combination of cyclophosphamide (40 mg/kg) and doxorubicin (4 mg/kg). All subjects were tested for anxiety, locomotor activity, working, visual and spatial memory consecutively. Although anxiety and visual memory were not affected, chemotherapy significantly decreased locomotor activity and impaired working and spatial memory in female rats, independent of their hormonal status. The cognitive deficits observed are hippocampal dependent. Therefore, as a first step to identity the potential signaling pathways involved in this cognitive dysfunction, the protein levels of extracellular signal-regulated kinase 1/2 (Erk1/2), Akt (neuroprotectant) BDNF and (structural protein) PSD95 in hippocampal lysates were measured. Erk1/2 and Akt pathways are known to modulate synaptic plasticity, neuronal survival, aging and cancer. We found an increased activation of Erk1/2 and Akt as well as an increase in the protein levels of PSD95 in OVX female rodents. However, OVX females had a higher overall BDNF level, independent of chemotherapy. These studies provide additional evidence that commonly used chemotherapeutic agents affect cognitive function and impact synaptic plasticity/aging molecules which may be part of the underlying biology explaining cognitive change and can be potential therapeutic targets.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.