Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE.
Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE.
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DOI：
10.1016/j.nbd.2022.105915
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发表时间：
2022-12
影响因子：
6.1
通讯作者：
Rebeck, G. William
中科院分区：
文献类型：
--
作者：
Ng, Christi Anne S.;Biran, Lucas P.;Galvano, Elena;Mandelblatt, Jeanne;Vicini, Stefano;Rebeck, G. William
许多癌症幸存者都会经历癌症相关的认知障碍（CRCI），其特点是化疗和/或激素治疗后出现注意力、工作记忆和执行功能问题。 APOE4 是阿尔茨海默病 (AD) 最强的遗传风险因素，也是 CRCI 的风险因素，尤其是在接受化疗的幸存者中。我们使用淀粉样蛋白 (5XFAD) 小鼠模型以及人类 APOE 的 E3 或 E4 等位基因（E3FAD 和 E4FAD），探讨了 APOE 基因型对化疗的影响是否与 AD 病理过程的增加相关。六个月大的雌性 E3FAD 小鼠（对照 n = 5，治疗 n = 5）和 E4FAD（对照 n = 6，治疗 n = 6）用两剂阿霉素（总计 10 mg/kg）或 DMSO 载体治疗。六周后，对小鼠实施安乐死，并通过免疫组织化学和生化分析对大脑进行分析。通过 6E10 免疫组织化学、Aβ40 和 Aβ42 ELISA 以及斑块形态测量，阿霉素治疗的小鼠大脑中 Aβ 水平与对照小鼠相同。阿霉素显着增加星形胶质细胞对 Aβ 沉积物的反应水平，这与 APOE 基因型无关；没有观察到阿霉素对小胶质细胞反应的影响。这些数据与阿霉素对 CRCI 风险的影响与淀粉样蛋白积累无关的模型一致，但可能与神经胶质细胞对损伤的反应有关。
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.
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影响因子：
11
作者：
Haage, Verena;De Jager, Philip L.
通讯作者：
De Jager, Philip L.
影响因子：
30.8
作者：
Chia R;Sabir MS;Bandres-Ciga S;Saez-Atienzar S;Reynolds RH;Gustavsson E;Walton RL;Ahmed S;Viollet C;Ding J;Makarious MB;Diez-Fairen M;Portley MK;Shah Z;Abramzon Y;Hernandez DG;Blauwendraat C;Stone DJ;Eicher J;Parkkinen L;Ansorge O;Clark L;Honig LS;Marder K;Lemstra A;St George-Hyslop P;Londos E;Morgan K;Lashley T;Warner TT;Jaunmuktane Z;Galasko D;Santana I;Tienari PJ;Myllykangas L;Oinas M;Cairns NJ;Morris JC;Halliday GM;Van Deerlin VM;Trojanowski JQ;Grassano M;Calvo A;Mora G;Canosa A;Floris G;Bohannan RC;Brett F;Gan-Or Z;Geiger JT;Moore A;May P;Krüger R;Goldstein DS;Lopez G;Tayebi N;Sidransky E;American Genome Center;Norcliffe-Kaufmann L;Palma JA;Kaufmann H;Shakkottai VG;Perkins M;Newell KL;Gasser T;Schulte C;Landi F;Salvi E;Cusi D;Masliah E;Kim RC;Caraway CA;Monuki ES;Brunetti M;Dawson TM;Rosenthal LS;Albert MS;Pletnikova O;Troncoso JC;Flanagan ME;Mao Q;Bigio EH;Rodríguez-Rodríguez E;Infante J;Lage C;González-Aramburu I;Sanchez-Juan P;Ghetti B;Keith J;Black SE;Masellis M;Rogaeva E;Duyckaerts C;Brice A;Lesage S;Xiromerisiou G;Barrett MJ;Tilley BS;Gentleman S;Logroscino G;Serrano GE;Beach TG;McKeith IG;Thomas AJ;Attems J;Morris CM;Palmer L;Love S;Troakes C;Al-Sarraj S;Hodges AK;Aarsland D;Klein G;Kaiser SM;Woltjer R;Pastor P;Bekris LM;Leverenz JB;Besser LM;Kuzma A;Renton AE;Goate A;Bennett DA;Scherzer CR;Morris HR;Ferrari R;Albani D;Pickering-Brown S;Faber K;Kukull WA;Morenas-Rodriguez E;Lleó A;Fortea J;Alcolea D;Clarimon J;Nalls MA;Ferrucci L;Resnick SM;Tanaka T;Foroud TM;Graff-Radford NR;Wszolek ZK;Ferman T;Boeve BF;Hardy JA;Topol EJ;Torkamani A;Singleton AB;Ryten M;Dickson DW;Chiò A;Ross OA;Gibbs JR;Dalgard CL;Traynor BJ;Scholz SW
通讯作者：
Scholz SW
影响因子：
6.2
作者：
Jansen, CE;Miaskowski, C;Kramer, J
通讯作者：
Kramer, J
DOI：
10.1073/pnas.0812697106
发表时间：
2009-02-10
影响因子：
11.1
作者：
Agosta, Federica;Vossel, Keith A.;Gorno-Tempini, Maria Luisa
通讯作者：
Gorno-Tempini, Maria Luisa
影响因子：
45.3
作者：
Ahles, Tim A.;Saykin, Andrew J.;Kaufman, Peter A.
通讯作者：
Kaufman, Peter A.