Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer

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Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer. / Rendeiro, Catarina; Sheriff, Andrew; Bhattacharya, Tushar K; Gogola, Joseph V; Baxter, Jeffrey H; Chen, Hong; Helferich, William G; Roy, Edward J; Rhodes, Justin S.

In: Behavioural Brain Research, Vol. 315, 15.12.2016, p. 10-22.

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APA

Rendeiro, C., Sheriff, A., Bhattacharya, T. K., Gogola, J. V., Baxter, J. H., Chen, H., Helferich, W. G., Roy, E. J., & Rhodes, J. S. (2016). Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer. Behavioural Brain Research, 315, 10-22. https://doi.org/10.1016/j.bbr.2016.07.043

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Rendeiro, Catarina ; Sheriff, Andrew ; Bhattacharya, Tushar K ; Gogola, Joseph V ; Baxter, Jeffrey H ; Chen, Hong ; Helferich, William G ; Roy, Edward J ; Rhodes, Justin S. / Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer. In: Behavioural Brain Research. 2016 ; Vol. 315. pp. 10-22.

Bibtex

@article{0cdd7e0387b34064a03223ab794af3b5,
title = "Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer",
abstract = "The negative impact of chemotherapy on cognitive function in cancer patients has gained increasing attention in the last decade. Whilst the short-term acute effects on cognition are expected following chemotherapy, the persistence of such impairments in the long-term is still in question. This is despite clinical evidence indicating cognitive difficulties may persist well beyond treatment and affect quality of life. In the present study, we assessed the long-term (3 months) cognitive impact of chemotherapy in a mouse model intended to mimic the human female post-menopausal population receiving chemotherapy for breast cancer. Ovariectomized, female, C57BL/6J mice received two doses of Doxorubicin, Cyclophosphamide, and 5-Fluorouracil or saline vehicle (control), separated by one week. During this interval, mice received BrdU injections to label dividing cells. Results indicate a persistent impairment in learning and recall (1h, 24h and 48h) on the Morris water maze, reduced survival and differentiation of new neurons (BrdU+/NeuN+), and a persistent decline in proliferation of new cells (Ki67(+)) in the dentate gyrus. Locomotor activity, motor performance, and anxiety-like behavior were unaffected. We further evaluated the efficacy of a diet enriched in omega-3-fatty acids (DHA+EPA+DPA), in reversing long-term chemotherapy deficits but no rescue was observed. The model described produces long-term cognitive and cellular impairments from chemotherapy that mimic those observed in humans. It could be useful for identifying mechanisms of action and to test further the ability of lifestyle interventions (e.g., diet) for ameliorating chemotherapy-induced cognitive impairments.",
keywords = "Animals, Antineoplastic Agents, Breast Neoplasms, Cell Count, Cell Differentiation, Cell Proliferation, Cyclophosphamide, Doxorubicin, Exploratory Behavior, Fatty Acids, Omega-3, Female, Fluorouracil, Ki-67 Antigen, Memory Disorders, Mice, Mice, Inbred C57BL, Neurogenesis, Ovariectomy, Phosphopyruvate Hydratase, Spatial Learning, Journal Article, Research Support, Non-U.S. Gov't",
author = "Catarina Rendeiro and Andrew Sheriff and Bhattacharya, {Tushar K} and Gogola, {Joseph V} and Baxter, {Jeffrey H} and Hong Chen and Helferich, {William G} and Roy, {Edward J} and Rhodes, {Justin S}",
note = "Published by Elsevier B.V.",
year = "2016",
month = dec,
day = "15",
doi = "10.1016/j.bbr.2016.07.043",
language = "English",
volume = "315",
pages = "10--22",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer

AU - Rendeiro, Catarina

AU - Sheriff, Andrew

AU - Bhattacharya, Tushar K

AU - Gogola, Joseph V

AU - Baxter, Jeffrey H

AU - Chen, Hong

AU - Helferich, William G

AU - Roy, Edward J

AU - Rhodes, Justin S

N1 - Published by Elsevier B.V.

PY - 2016/12/15

Y1 - 2016/12/15

N2 - The negative impact of chemotherapy on cognitive function in cancer patients has gained increasing attention in the last decade. Whilst the short-term acute effects on cognition are expected following chemotherapy, the persistence of such impairments in the long-term is still in question. This is despite clinical evidence indicating cognitive difficulties may persist well beyond treatment and affect quality of life. In the present study, we assessed the long-term (3 months) cognitive impact of chemotherapy in a mouse model intended to mimic the human female post-menopausal population receiving chemotherapy for breast cancer. Ovariectomized, female, C57BL/6J mice received two doses of Doxorubicin, Cyclophosphamide, and 5-Fluorouracil or saline vehicle (control), separated by one week. During this interval, mice received BrdU injections to label dividing cells. Results indicate a persistent impairment in learning and recall (1h, 24h and 48h) on the Morris water maze, reduced survival and differentiation of new neurons (BrdU+/NeuN+), and a persistent decline in proliferation of new cells (Ki67(+)) in the dentate gyrus. Locomotor activity, motor performance, and anxiety-like behavior were unaffected. We further evaluated the efficacy of a diet enriched in omega-3-fatty acids (DHA+EPA+DPA), in reversing long-term chemotherapy deficits but no rescue was observed. The model described produces long-term cognitive and cellular impairments from chemotherapy that mimic those observed in humans. It could be useful for identifying mechanisms of action and to test further the ability of lifestyle interventions (e.g., diet) for ameliorating chemotherapy-induced cognitive impairments.

AB - The negative impact of chemotherapy on cognitive function in cancer patients has gained increasing attention in the last decade. Whilst the short-term acute effects on cognition are expected following chemotherapy, the persistence of such impairments in the long-term is still in question. This is despite clinical evidence indicating cognitive difficulties may persist well beyond treatment and affect quality of life. In the present study, we assessed the long-term (3 months) cognitive impact of chemotherapy in a mouse model intended to mimic the human female post-menopausal population receiving chemotherapy for breast cancer. Ovariectomized, female, C57BL/6J mice received two doses of Doxorubicin, Cyclophosphamide, and 5-Fluorouracil or saline vehicle (control), separated by one week. During this interval, mice received BrdU injections to label dividing cells. Results indicate a persistent impairment in learning and recall (1h, 24h and 48h) on the Morris water maze, reduced survival and differentiation of new neurons (BrdU+/NeuN+), and a persistent decline in proliferation of new cells (Ki67(+)) in the dentate gyrus. Locomotor activity, motor performance, and anxiety-like behavior were unaffected. We further evaluated the efficacy of a diet enriched in omega-3-fatty acids (DHA+EPA+DPA), in reversing long-term chemotherapy deficits but no rescue was observed. The model described produces long-term cognitive and cellular impairments from chemotherapy that mimic those observed in humans. It could be useful for identifying mechanisms of action and to test further the ability of lifestyle interventions (e.g., diet) for ameliorating chemotherapy-induced cognitive impairments.

KW - Animals

KW - Antineoplastic Agents

KW - Breast Neoplasms

KW - Cell Count

KW - Cell Differentiation

KW - Cell Proliferation

KW - Cyclophosphamide

KW - Doxorubicin

KW - Exploratory Behavior

KW - Fatty Acids, Omega-3

KW - Female

KW - Fluorouracil

KW - Ki-67 Antigen

KW - Memory Disorders

KW - Mice

KW - Mice, Inbred C57BL

KW - Neurogenesis

KW - Ovariectomy

KW - Phosphopyruvate Hydratase

KW - Spatial Learning

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.bbr.2016.07.043

DO - 10.1016/j.bbr.2016.07.043

M3 - Article

C2 - 27478140

VL - 315

SP - 10

EP - 22

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -