Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice
IntroductionTamoxifen is a common treatment for estrogen receptor-positive breast cancer. While tamoxifen treatment is generally accepted as safe, there are concerns about adverse effects on cognition.MethodsWe used a mouse model of chronic tamoxifen exposure to examine the effects of tamoxifen on t...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnins.2023.1068334/full |
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| author | Elena Galvano Harshul Pandit Jordy Sepulveda Christi Anne S. Ng Melanie K. Becher Jeanne S. Mandelblatt Kathleen Van Dyk G. William Rebeck |
| author_facet | Elena Galvano Harshul Pandit Jordy Sepulveda Christi Anne S. Ng Melanie K. Becher Jeanne S. Mandelblatt Kathleen Van Dyk G. William Rebeck |
| author_sort | Elena Galvano |
| collection | DOAJ |
| description | IntroductionTamoxifen is a common treatment for estrogen receptor-positive breast cancer. While tamoxifen treatment is generally accepted as safe, there are concerns about adverse effects on cognition.MethodsWe used a mouse model of chronic tamoxifen exposure to examine the effects of tamoxifen on the brain. Female C57/BL6 mice were exposed to tamoxifen or vehicle control for six weeks; brains of 15 mice were analyzed for tamoxifen levels and transcriptomic changes, and an additional 32 mice were analyzed through a battery of behavioral tests.ResultsTamoxifen and its metabolite 4-OH-tamoxifen were found at higher levels in the brain than in the plasma, demonstrating the facile entry of tamoxifen into the CNS. Behaviorally, tamoxifen-exposed mice showed no impairment in assays related to general health, exploration, motor function, sensorimotor gating, and spatial learning. Tamoxifen-treated mice showed a significantly increased freezing response in a fear conditioning paradigm, but no effects on anxiety measures in the absence of stressors. RNA sequencing analysis of whole hippocampi showed tamoxifen-induced reductions in gene pathways related to microtubule function, synapse regulation, and neurogenesis.DiscussionThese findings of the effects of tamoxifen exposure on fear conditioning and on gene expression related to neuronal connectivity suggest that there may be CNS side effects of this common breast cancer treatment. |
| first_indexed | 2024-04-10T15:54:32Z |
| format | Article |
| id | doaj.art-0caf651bc3014370b5cc81bca03cb233 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-04-10T15:54:32Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-0caf651bc3014370b5cc81bca03cb2332023-02-10T14:35:36ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-02-011710.3389/fnins.2023.10683341068334Behavioral and transcriptomic effects of the cancer treatment tamoxifen in miceElena Galvano0Harshul Pandit1Jordy Sepulveda2Christi Anne S. Ng3Melanie K. Becher4Jeanne S. Mandelblatt5Kathleen Van Dyk6G. William Rebeck7Department of Neuroscience, Georgetown University Medical Center, Washington, DC, United StatesDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC, United StatesDepartment of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC, United StatesDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC, United StatesDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC, United StatesDepartment of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, United StatesDepartment of Psychiatry, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, United StatesDepartment of Neuroscience, Georgetown University Medical Center, Washington, DC, United StatesIntroductionTamoxifen is a common treatment for estrogen receptor-positive breast cancer. While tamoxifen treatment is generally accepted as safe, there are concerns about adverse effects on cognition.MethodsWe used a mouse model of chronic tamoxifen exposure to examine the effects of tamoxifen on the brain. Female C57/BL6 mice were exposed to tamoxifen or vehicle control for six weeks; brains of 15 mice were analyzed for tamoxifen levels and transcriptomic changes, and an additional 32 mice were analyzed through a battery of behavioral tests.ResultsTamoxifen and its metabolite 4-OH-tamoxifen were found at higher levels in the brain than in the plasma, demonstrating the facile entry of tamoxifen into the CNS. Behaviorally, tamoxifen-exposed mice showed no impairment in assays related to general health, exploration, motor function, sensorimotor gating, and spatial learning. Tamoxifen-treated mice showed a significantly increased freezing response in a fear conditioning paradigm, but no effects on anxiety measures in the absence of stressors. RNA sequencing analysis of whole hippocampi showed tamoxifen-induced reductions in gene pathways related to microtubule function, synapse regulation, and neurogenesis.DiscussionThese findings of the effects of tamoxifen exposure on fear conditioning and on gene expression related to neuronal connectivity suggest that there may be CNS side effects of this common breast cancer treatment.https://www.frontiersin.org/articles/10.3389/fnins.2023.1068334/fulltamoxifenchemotherapyblood-brain barriertranscriptomic (RNA-seq)behaviormouse model |
| spellingShingle | Elena Galvano Harshul Pandit Jordy Sepulveda Christi Anne S. Ng Melanie K. Becher Jeanne S. Mandelblatt Kathleen Van Dyk G. William Rebeck Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice Frontiers in Neuroscience tamoxifen chemotherapy blood-brain barrier transcriptomic (RNA-seq) behavior mouse model |
| title | Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice |
| title_full | Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice |
| title_fullStr | Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice |
| title_full_unstemmed | Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice |
| title_short | Behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice |
| title_sort | behavioral and transcriptomic effects of the cancer treatment tamoxifen in mice |
| topic | tamoxifen chemotherapy blood-brain barrier transcriptomic (RNA-seq) behavior mouse model |
| url | https://www.frontiersin.org/articles/10.3389/fnins.2023.1068334/full |
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