ArticleBiochemical and biophysical research communications2016
Identification of early gene expression changes in primary cultured neurons treated with topoisomerase I poisons.
Article in Biochemical and biophysical research communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 5 citations in OpenAlex.
- Exploring the material basis and molecular targets of Changma Xifeng tablet in treating Tourette syndrome: an integrative approach of network pharmacology and miRNA analysis.Metabolic brain disease · 2024Article
- Chronic defects in intraspinal mechanisms of spike encoding by spinal motoneurons following chemotherapy.Experimental neurology · 2020Article
- High accuracy gene expression profiling of sorted cell subpopulations from breast cancer PDX model tissue.PloS one · 2020Article
- Peroxisomes contribute to oxidative stress in neurons during doxorubicin-based chemotherapy.Molecular and cellular neurosciences · 2018Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Topoisomerase 1 (TOP1) poisons like camptothecin (CPT) are currently used in cancer chemotherapy but these compounds can have damaging, off-target effects on neurons leading to cognitive, sensory and motor deficits. To understand the molecular basis for the enhanced sensitivity of neurons to CPT, we examined the effects of compounds that inhibit TOP1-CPT, actinomycin D (ActD) and β-lapachone (β-Lap)-on primary cultured rat motor (MN) and cortical (CN) neurons as well as fibroblasts. Neuronal cells expressed higher levels of Top1 mRNA than fibroblasts but transcript levels are reduced in all cell types after treatment with CPT. Microarray analysis was performed to identify differentially regulated transcripts in MNs in response to a brief exposure to CPT. Pathway analysis of the differentially expressed transcripts revealed activation of ERK and JNK signaling cascades in CPT-treated MNs. Immediate-early genes like Fos, Egr-1 and Gadd45b were upregulated in CPT-treated MNs. Fos mRNA levels were elevated in all cell types treated with CPT; Egr-1, Gadd45b and Dyrk3 transcript levels, however, increased in CPT-treated MNs and CNs but decreased in CPT-treated fibroblasts. These transcripts may represent new targets for the development of therapeutic agents that mitigate the off-target effects of chemotherapy on the nervous system.
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