Dynamin-1 is a potential mediator in cancer-related cognitive impairment
Dynamin-1 (DNM1) is crucial for synaptic activity, neurotransmission, and associative memory, positioning it as a potential biomarker of cancer-related cognitive impairment (CRCI), a neurological consequence of cancer treatment characterized by memory loss, poor concentration, and impaired executive...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Neurotherapeutics |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878747924001673 |
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| author | Ding Quan Ng Casey Hudson Tracy Nguyen Sukesh Kumar Gupta Yong Qin Koh Munjal M. Acharya Alexandre Chan |
| author_facet | Ding Quan Ng Casey Hudson Tracy Nguyen Sukesh Kumar Gupta Yong Qin Koh Munjal M. Acharya Alexandre Chan |
| author_sort | Ding Quan Ng |
| collection | DOAJ |
| description | Dynamin-1 (DNM1) is crucial for synaptic activity, neurotransmission, and associative memory, positioning it as a potential biomarker of cancer-related cognitive impairment (CRCI), a neurological consequence of cancer treatment characterized by memory loss, poor concentration, and impaired executive function. Through a stepwise approach, this study investigated the role of DNM1 in CRCI pathogenesis, incorporating both human data and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Following that, a syngeneic young-adult WT (C57BL/6) female mouse model of breast cancer chemobrain was developed to study DNM1 expression in the hippocampus. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were 32 % lower (P = 0.041) among cancer participants compared to non-cancer prior to treatment. After receiving cytotoxic treatment, cognitively impaired cancer patients were found to have 46 % lower DNM1 levels than those without impairment (P = 0.049). In murine breast cancer-bearing mice receiving chemotherapy, we found a greater than 40 % decline (P < 0.0001) in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions concurrent with a deterioration in spatial recognition memory (P < 0.02), compared to control mice without exposure to cancer and chemotherapy. Consistently observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. DNM1 might be a biomarker and therapeutic target for CRCI. |
| format | Article |
| id | doaj-art-db9c7caa305e4f8e8a5290b47ce94a4f |
| institution | Kabale University |
| issn | 1878-7479 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurotherapeutics |
| spelling | doaj-art-db9c7caa305e4f8e8a5290b47ce94a4f2025-02-01T04:11:52ZengElsevierNeurotherapeutics1878-74792025-01-01221e00480Dynamin-1 is a potential mediator in cancer-related cognitive impairmentDing Quan Ng0Casey Hudson1Tracy Nguyen2Sukesh Kumar Gupta3Yong Qin Koh4Munjal M. Acharya5Alexandre Chan6Department of Clinical Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USADepartment of Anatomy & Neurobiology, School of Medicine, University of California Irvine, Irvine, CA, USADepartment of Anatomy & Neurobiology, School of Medicine, University of California Irvine, Irvine, CA, USADepartment of Anatomy & Neurobiology, School of Medicine, University of California Irvine, Irvine, CA, USADepartment of Clinical Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USADepartment of Anatomy & Neurobiology, School of Medicine, University of California Irvine, Irvine, CA, USA; Department of Radiation Oncology, School of Medicine, University of California Irvine, Irvine, CA, USA; Corresponding authors.Department of Clinical Pharmacy Practice, School of Pharmacy & Pharmaceutical Sciences, University of California Irvine, Irvine, CA, USA; Department of Oncology Pharmacy, National Cancer Centre Singapore, Singapore; Corresponding authors.Dynamin-1 (DNM1) is crucial for synaptic activity, neurotransmission, and associative memory, positioning it as a potential biomarker of cancer-related cognitive impairment (CRCI), a neurological consequence of cancer treatment characterized by memory loss, poor concentration, and impaired executive function. Through a stepwise approach, this study investigated the role of DNM1 in CRCI pathogenesis, incorporating both human data and animal models. The human study recruited newly diagnosed, chemotherapy-naïve adolescent and young adult cancer and non-cancer controls to complete a cognitive instrument (FACT-Cog) and blood draws for up to three time points. Following that, a syngeneic young-adult WT (C57BL/6) female mouse model of breast cancer chemobrain was developed to study DNM1 expression in the hippocampus. Samples from eighty-six participants with 30 adolescent and young adult (AYA) cancer and 56 non-cancer participants were analyzed. DNM1 levels were 32 % lower (P = 0.041) among cancer participants compared to non-cancer prior to treatment. After receiving cytotoxic treatment, cognitively impaired cancer patients were found to have 46 % lower DNM1 levels than those without impairment (P = 0.049). In murine breast cancer-bearing mice receiving chemotherapy, we found a greater than 40 % decline (P < 0.0001) in DNM1 immunoreactivity in the hippocampal CA1 and CA3 subregions concurrent with a deterioration in spatial recognition memory (P < 0.02), compared to control mice without exposure to cancer and chemotherapy. Consistently observed in both human and animal studies, the downregulation of DNM1 is linked with the onset of CRCI. DNM1 might be a biomarker and therapeutic target for CRCI.http://www.sciencedirect.com/science/article/pii/S1878747924001673Cancer-related cognitive impairmentChemobrainDynamin-1Extracellular vesicleExosome |
| spellingShingle | Ding Quan Ng Casey Hudson Tracy Nguyen Sukesh Kumar Gupta Yong Qin Koh Munjal M. Acharya Alexandre Chan Dynamin-1 is a potential mediator in cancer-related cognitive impairment Neurotherapeutics Cancer-related cognitive impairment Chemobrain Dynamin-1 Extracellular vesicle Exosome |
| title | Dynamin-1 is a potential mediator in cancer-related cognitive impairment |
| title_full | Dynamin-1 is a potential mediator in cancer-related cognitive impairment |
| title_fullStr | Dynamin-1 is a potential mediator in cancer-related cognitive impairment |
| title_full_unstemmed | Dynamin-1 is a potential mediator in cancer-related cognitive impairment |
| title_short | Dynamin-1 is a potential mediator in cancer-related cognitive impairment |
| title_sort | dynamin 1 is a potential mediator in cancer related cognitive impairment |
| topic | Cancer-related cognitive impairment Chemobrain Dynamin-1 Extracellular vesicle Exosome |
| url | http://www.sciencedirect.com/science/article/pii/S1878747924001673 |
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