Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s disease (doi:10.34691/UCHILE/UYC3UR)

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Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s disease

doi:10.34691/UCHILE/UYC3UR

Repositorio de datos de investigación de la Universidad de Chile

2025-12-04

2

Barbara Bruna Jara; Jamileth More; Pedro Lobos Zambrano; Daniela Paz Ponce de la Vega; Claudia Duran-Aniotz; Jose Luis Valdés; Maria Alejandra Gleisner; Fabian Tempio; Felipe Salech; Matías Pizarro; Carol D SanMartín; Martín Cárcamo; Andrew Quest; Mercedes Lopez; Flavio Salazar O; Maria Isabel Behrens, 2025, "Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s disease", https://doi.org/10.34691/UCHILE/UYC3UR, Repositorio de datos de investigación de la Universidad de Chile, V2, UNF:6:nVCODfzbWscGFgmS53OoYA== [fileUNF]

Melanoma cell inoculation improves cognitive impairment in the 5xFAD mouse model of Alzheimer’s disease

doi:10.34691/UCHILE/UYC3UR

Barbara Bruna Jara (Universidad de Chile)

Jamileth More (Universidad de Chile)

Pedro Lobos Zambrano (Universidad de Chile)

Daniela Paz Ponce de la Vega (Universidad de Chile)

Claudia Duran-Aniotz (Universidad Aldolfo Ibañez)

Jose Luis Valdés (Universidad de Chile)

Maria Alejandra Gleisner (Universidad de Chile)

Fabian Tempio (Universidad de Chile)

Felipe Salech (Universidad de Chile)

Matías Pizarro (Universidad Aldolfo Ibañez)

Carol D SanMartín (INTA)

Martín Cárcamo (CICA)

Andrew Quest (Universidad de Chile)

Mercedes Lopez (Universidad de Chile)

Flavio Salazar O (Universidad de Chile)

Maria Isabel Behrens (Universidad de Chile)

Repositorio de datos de investigación de la Universidad de Chile

María Isabel Behrens

Bruna Jara, Barbara

2025-12-02

https://doi.org/10.34691/UCHILE/UYC3UR

Medicine, Health and Life Sciences, Alzheimer, Cancer

The inverse association between Alzheimer’s disease (AD) and cancer reported in epidemiological studies remains poorly understood. We injected melanoma B16F0 cells or saline into 5xFAD transgenic AD mice and wildtype (WT) controls and monitored tumor growth and cognitive performance (Y maze, Oasis maze) over 28 days. Melanoma- inoculated 5xFAD mice (5xFAD/B16F0) demonstrated improved cognition compared to 5xFAD/saline, regardless of tumor development, suggesting a systemic immune effect rather than one driven by tumor growth. 5xFAD/B16F0 mice also showed reduced tumor incidence than WT mice, as well as an increased number of splenic myeloid cells. Although amyloid-β levels and the number of astrocytes and microglia were unchanged, microglial soma area in the hippocampus was reduced in 5xFAD/B16F0, suggesting a shift toward a less reactive microglial phenotype. These results suggest that peripheral immune activation may modulate microglia in the hippocampus, offering preliminary insights into the biological basis of the AD and cancer inverse relationship.

BB performed the experiments and analyzed, and interpreted the data regarding the experimental studies of cognitive behavior and neuropathological experiments, and was a major contributor in the writing of the manuscript. JM performed the experiments and analyzed and interpreted the data regarding the experimental studies of cognitive behavior and neuropathological experiments, and was a major contributor in the writing of the manuscript. DPP managed the experimental design and analyzed and interpreted the results. CDA contributed to the determination of amyloid staining and analyzed and interpreted the data. PL contributed to the analysis and quantification of amyloid plaque staining. AG performed the immunological analysis in the brains and spleens of transgenic and WT mice. FT performed immunological analysis on the brains and spleens of transgenic and WT mice. FS contributed to the conceptual design of the study and the analysis of the results. MP contributed to the determination of amyloid staining. CSM contributed to the conceptual design of the research and analysis of the results. MC contributed to the conceptual design of the research and analysis of the results. AFGQ contributed to the conceptual design of the research and analysis of the results, ML contributed to the analytic discussion of the immunological results. FS-O contributed to the analytic discussion of the immunological results and text revision. MIB contributed to the experimental design, analysis, and interpretation of the results, and was a major contributor to the writing of the manuscript. All authors read and approved the final manuscript.

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Summary Statistics: Valid 23.0; Mean 0.1432463768115942; StDev 0.10860558877444328; Max. 0.329; Min. 0.016;

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Summary Statistics: Mean 0.18197826086956523; StDev 0.15077187182698135; Min. 0.009; Max. 0.451; Valid 23.0

Variable Format: numeric

Notes: UNF:6:5mhZh7QxL254D+cBMVWufg==

f5203 Location:

Summary Statistics: StDev 0.11674956337179178; Min. 0.013; Valid 24.0; Max. 0.372; Mean 0.14972222222222223;

Variable Format: numeric

Notes: UNF:6:Qob0MUSTWbW+wRfzja/xAg==

f5203 Location:

Summary Statistics: Min. 0.016; Valid 22.0; Mean 0.25815151515151513; StDev 0.23815887115043163; Max. 0.816;

Variable Format: numeric

Notes: UNF:6:qtB3rbWZ+93MOEeTvtYAdQ==

f5203 Location:

Summary Statistics: Mean 0.2677777777777778; Max. 0.503; Min. 0.045; Valid 12.0; StDev 0.14227973111276915;

Variable Format: numeric

Notes: UNF:6:gQZpdv/cPUAESvPX94Fz7A==

f5203 Location:

Summary Statistics: Mean 0.558; StDev 0.0; Max. 0.558; Min. 0.558; Valid 2.0;

Variable Format: numeric

Notes: UNF:6:Q+2j5251g5TCp/pdTSCtpg==

f5203 Location:

Summary Statistics: Max. 0.571; Mean 0.4303333333333333; StDev 0.11637964694147436; Min. 0.286; Valid 4.0

Variable Format: numeric

Notes: UNF:6:TREiZbn5fIW9YhlPzMgJzw==

f5203 Location:

Summary Statistics: StDev 0.11309729219103712; Mean 0.15840396825396827; Valid 6.0; Max. 0.34240000000000004; Min. 0.050976190476190474

Variable Format: numeric

Notes: UNF:6:aRNZnRClWr7joWmloKUw3g==

f5203 Location:

Summary Statistics: Max. NaN; Min. NaN; StDev NaN; Mean NaN; Valid 0.0

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Max. NaN; Min. NaN; StDev NaN; Valid 0.0; Mean NaN;

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Variable Format: character

Notes: UNF:6:ds35bpo6R+/4OtVNrkyNNQ==

f5203 Location:

Variable Format: character

Notes: UNF:6:jBuDwzOwrfzHhNaBE/inDA==

f5203 Location:

Summary Statistics: Min. 0.019; Valid 27.0; StDev 0.146562153850976; Mean 0.20037654320987655; Max. 0.541;

Variable Format: numeric

Notes: UNF:6:AX3JhjGVXx7FIdy60CuVdg==

f5203 Location:

Summary Statistics: Min. 0.01; Max. 0.678; Valid 27.0; StDev 0.15548253958925962; Mean 0.19754938271604938

Variable Format: numeric

Notes: UNF:6:5SFUPiryLFgDowqKWBHK+A==

f5203 Location:

Summary Statistics: StDev 0.0921489949210368; Min. 0.004; Max. 0.358; Mean 0.13694871794871796; Valid 26.0;

Variable Format: numeric

Notes: UNF:6:drNZkrdtJUd2ltwoqdYWjg==

f5203 Location:

Summary Statistics: Valid 27.0; Min. 0.013; Max. 0.389; StDev 0.1037854166524289; Mean 0.19110493827160493;

Variable Format: numeric

Notes: UNF:6:mpYmG9ZTkvZ5ZTTp7pH6PQ==

f5203 Location:

Summary Statistics: Valid 27.0; Mean 0.14364814814814814; Min. 0.018; StDev 0.07817767312665794; Max. 0.31

Variable Format: numeric

Notes: UNF:6:QMj4I7Wj8Jf4XfsXVxkhyw==

f5203 Location:

Summary Statistics: Max. 0.507; Min. 0.029; Mean 0.1783888888888889; StDev 0.11408436858833762; Valid 24.0;

Variable Format: numeric

Notes: UNF:6:+KO6VRumABskmCSxox3n3A==

f5203 Location:

Summary Statistics: Mean 0.18938405797101449; Min. 0.05; StDev 0.1108986414420549; Max. 0.492; Valid 23.0

Variable Format: numeric

Notes: UNF:6:ExuiEDM7gUCCu51fpzuQWw==

f5203 Location:

Summary Statistics: StDev 0.08869144539792148; Min. 0.061; Max. 0.4; Mean 0.1691777777777778; Valid 15.0

Variable Format: numeric

Notes: UNF:6:/8mT557oHwEijJ9Jb5LKZQ==

f5203 Location:

Summary Statistics: Min. 0.377; Mean 0.49933333333333335; StDev 0.1645931009759792; Valid 4.0; Max. 0.732

Variable Format: numeric

Notes: UNF:6:7PMZfKeT9XxXuI8qZ1TxTw==

f5203 Location:

Summary Statistics: Mean NaN; StDev NaN; Min. NaN; Valid 0.0; Max. NaN;

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Min. 0.07352380952380952; StDev 0.08895184921365905; Max. 0.28853703703703704; Mean 0.18057637944066515; Valid 7.0

Variable Format: numeric

Notes: UNF:6:vAor7LR/a1U0Ggkl3u6atA==

f5203 Location:

Summary Statistics: StDev NaN; Min. NaN; Mean NaN; Valid 0.0; Max. NaN;

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Min. NaN; Valid 0.0; Mean NaN; StDev NaN; Max. NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Mean NaN; Valid 0.0; Min. NaN; Max. NaN; StDev NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Max. NaN; Mean NaN; Min. NaN; Valid 0.0; StDev NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Max. NaN; Valid 0.0; Min. NaN; Mean NaN; StDev NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Valid 0.0; Min. NaN; Max. NaN; StDev NaN; Mean NaN;

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Max. NaN; Valid 0.0; StDev NaN; Min. NaN; Mean NaN;

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: Mean NaN; Valid 0.0; Min. NaN; Max. NaN; StDev NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: StDev NaN; Valid 0.0; Mean NaN; Min. NaN; Max. NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

f5203 Location:

Summary Statistics: StDev NaN; Valid 0.0; Max. NaN; Mean NaN; Min. NaN

Variable Format: numeric

Notes: UNF:6:dxM/Qx1eEt2FAALA09Tg/g==

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