ArticleActa neuropathologica communications2015
Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis.
Article in Acta neuropathologica communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 48 citations in OpenAlex.
- Profiles of neuropsychiatric toxicity associated with different endocrine therapies for breast cancer: a global pharmacovigilance study based on FAERS and VigiAccess.Frontiers in pharmacology · 2026Article
- RYGB induces vagal sensory neuropathy characterized by altered Glp1r expression and enhanced exendin-4 responsiveness in male mice.American journal of physiology. Endocrinology and metabolism · 2026Article
- Oligodendroglia-to-pericyte conversion after lipopolysaccharide exposure is gender-dependent.PloS one · 2024Article
- Early Effects of Alpha-Synuclein Depletion by Pan-Neuronal Inactivation of Encoding Gene on Electroencephalogram Coherence between Different Brain Regions in Mice.Biomedicines · 2023Article
- A method for TAT-Cre recombinase-mediated floxed allele modification in ex vivo tissue slices.Disease models & mechanisms · 2023Article
- Repurposing Tamoxifen for Tumor Microenvironment Priming and Enhanced Tumor-Targeted Drug Delivery.Advanced therapeutics · 2023Article
- Transfer of nuclear and ribosomal material from Sox10-lineage cells to neurons in the mouse brain.The Journal of experimental medicine · 2023Article
- DHCR24 reverses Alzheimer's disease-related pathology and cognitive impairment via increasing hippocampal cholesterol levels in 5xFAD mice.Acta neuropathologica communications · 2023Article
- Atf3 defines a population of pulmonary endothelial cells essential for lung regeneration.eLife · 2023Article
- Hippocampal neurons respond to brain activity with functional hypoxia.Molecular psychiatry · 2021Article
- Estrogen receptor alpha in the brain mediates tamoxifen-induced changes in physiology in mice.eLife · 2021Article
- Effects of tamoxifen therapy on sciatic nerve crush injury: An experimental study in rats.Acta orthopaedica et traumatologica turcica · 2021Article
- Endocrine disruptors also function as nervous disruptors and can be renamed endocrine and nervous disruptors (ENDs).Toxicology reports · 2021Review
- Delayed short-term tamoxifen treatment does not promote remyelination or neuron sparing after spinal cord injury.PloS one · 2020Article
- Mice lacking Kcns1 in peripheral neurons show increased basal and neuropathic pain sensitivity.Pain · 2018Article
- Translational Significance of Selective Estrogen Receptor Modulators in Psychiatric Disorders.International journal of endocrinology · 2018Review
- Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics.Scientific reports · 2017Article
- Use antibiotics in cell culture with caution: genome-wide identification of antibiotic-induced changes in gene expression and regulation.Scientific reports · 2017Article
- Tamoxifen Provides Structural and Functional Rescue in Murine Models of Photoreceptor Degeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundTamoxifen (TAM) is an important cancer therapeutic and an experimental tool for effecting genetic recombination using the inducible Cre-Lox technique. Despite its widespread use in the clinic and laboratory, we know little about its effects on the nervous system. This is of significant concern because TAM, via unknown mechanisms, induces cognitive impairment in humans. A hallmark of cellular stress is induction of Activating Transcription Factor 3 (Atf3), and so to determine whether TAM induces cellular stress in the adult nervous system, we generated a knock-in mouse in which Atf3 promoter activity drives transcription of TAM-dependent Cre recombinase (Cre-ERT2); when crossed with tdtomato reporter mice, Atf3 induction results in robust and permanent genetic labeling of cells in which it is up-regulated even transiently.
resultsWe found that granular neurons of the olfactory bulb and dentate gyrus, vascular cells and ependymal cells throughout the brain, and peripheral sensory neurons expressed tdtomato in response to TAM treatment. We also show that TAM induced Atf3 up-regulation through inhibition of cholesterol epoxide hydrolase (ChEH): reporter expression was mitigated by delivery in vitamin E-rich wheat germ oil (vitamin E depletes ChEH substrates), and was partially mimicked by a ChEH-specific inhibitor.
conclusionsThis work demonstrates that TAM stresses cells of the adult central and peripheral nervous systems and highlights concerns about clinical and experimental use of TAM. We propose TAM administration in vitamin E-rich vehicles such as wheat germ oil as a simple remedy.
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