Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE
Many cancer survivors experience cancer-related cognitive impairment (CRCI), which is characterized by problems of attention, working memory, and executive function following chemotherapy and/or hormonal treatment. APOE4, the strongest genetic risk factor for Alzheimer's Disease (AD), is also a...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122003072 |
| _version_ | 1811177789065265152 |
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| author | Christi Anne S. Ng Lucas P. Biran Elena Galvano Jeanne Mandelblatt Stefano Vicini G. William Rebeck |
| author_facet | Christi Anne S. Ng Lucas P. Biran Elena Galvano Jeanne Mandelblatt Stefano Vicini G. William Rebeck |
| author_sort | Christi Anne S. Ng |
| collection | DOAJ |
| description | Many cancer survivors experience cancer-related cognitive impairment (CRCI), which is characterized by problems of attention, working memory, and executive function following chemotherapy and/or hormonal treatment. APOE4, the strongest genetic risk factor for Alzheimer's Disease (AD), is also a risk factor for CRCI, especially among survivors exposed to chemotherapy. We explored whether the effects of APOE genotype to chemotherapy were associated with an increase in AD pathological processes, using a mouse model of amyloid (5XFAD) along with the E3 or E4 alleles of human APOE (E3FAD and E4FAD). Six-month-old female E3FAD mice (control n = 5, treated n = 5) and E4FAD (control n = 6, treated n = 6) were treated with two doses of doxorubicin (total 10 mg/kg) or DMSO vehicle. After six weeks, mice were euthanized and brains were analyzed by immunohistochemistry and biochemical assays. Doxorubicin-treated mice had the same level of Aβ in the brain as control mice, as measured by 6E10 immunohistochemistry, Aβ40 and Aβ42 ELISAs, and plaque morphologies. Doxorubicin significantly increased the level of the astrocytic response to Aβ deposits, which was independent of APOE genotype; no effects of doxorubicin were observed on the microglial responses. These data are consistent with a model in which the effects of doxorubicin on risk of CRCI are unrelated amyloid accumulation, but possibly related to glial responses to damage. |
| first_indexed | 2024-04-11T06:07:06Z |
| format | Article |
| id | doaj.art-0a4103d8ac614419bf60644ba43db267 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T06:07:06Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-0a4103d8ac614419bf60644ba43db2672022-12-22T04:41:27ZengElsevierNeurobiology of Disease1095-953X2022-12-01175105915Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOEChristi Anne S. Ng0Lucas P. Biran1Elena Galvano2Jeanne Mandelblatt3Stefano Vicini4G. William Rebeck5Department of Neuroscience, Georgetown University, Washington, DC, United States of AmericaDepartment of Neuroscience, Georgetown University, Washington, DC, United States of AmericaDepartment of Neuroscience, Georgetown University, Washington, DC, United States of AmericaDepartment of Oncology, Cancer Prevention and Control Program and Georgetown Lombardi Institute for Cancer and Aging Research, Georgetown University, Washington, DC, United States of AmericaDepartment of Pharmacology and Physiology, Georgetown University, Washington, DC, United States of America; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, United States of AmericaDepartment of Neuroscience, Georgetown University, Washington, DC, United States of America; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, United States of America; Corresponding author at: 3970 Reservoir Rd, NW, Washington, DC 20007, United States of America.Many cancer survivors experience cancer-related cognitive impairment (CRCI), which is characterized by problems of attention, working memory, and executive function following chemotherapy and/or hormonal treatment. APOE4, the strongest genetic risk factor for Alzheimer's Disease (AD), is also a risk factor for CRCI, especially among survivors exposed to chemotherapy. We explored whether the effects of APOE genotype to chemotherapy were associated with an increase in AD pathological processes, using a mouse model of amyloid (5XFAD) along with the E3 or E4 alleles of human APOE (E3FAD and E4FAD). Six-month-old female E3FAD mice (control n = 5, treated n = 5) and E4FAD (control n = 6, treated n = 6) were treated with two doses of doxorubicin (total 10 mg/kg) or DMSO vehicle. After six weeks, mice were euthanized and brains were analyzed by immunohistochemistry and biochemical assays. Doxorubicin-treated mice had the same level of Aβ in the brain as control mice, as measured by 6E10 immunohistochemistry, Aβ40 and Aβ42 ELISAs, and plaque morphologies. Doxorubicin significantly increased the level of the astrocytic response to Aβ deposits, which was independent of APOE genotype; no effects of doxorubicin were observed on the microglial responses. These data are consistent with a model in which the effects of doxorubicin on risk of CRCI are unrelated amyloid accumulation, but possibly related to glial responses to damage.http://www.sciencedirect.com/science/article/pii/S0969996122003072APOEAlzheimer'sChemotherapyDoxorubicinAmyloidGliosis |
| spellingShingle | Christi Anne S. Ng Lucas P. Biran Elena Galvano Jeanne Mandelblatt Stefano Vicini G. William Rebeck Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE Neurobiology of Disease APOE Alzheimer's Chemotherapy Doxorubicin Amyloid Gliosis |
| title | Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE |
| title_full | Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE |
| title_fullStr | Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE |
| title_full_unstemmed | Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE |
| title_short | Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE |
| title_sort | chemotherapy promotes astrocytic response to aβ deposition but not aβ levels in a mouse model of amyloid and apoe |
| topic | APOE Alzheimer's Chemotherapy Doxorubicin Amyloid Gliosis |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122003072 |
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