HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32665429
DOI
10.1158/1541-7786.mcr-20-0292
PII: 1541-7786.MCR-20-0292
Knihovny.cz E-resources
- MeSH
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels metabolism MeSH
- Humans MeSH
- Mice MeSH
- Neoplasms drug therapy MeSH
- Neural Stem Cells metabolism MeSH
- Cell Proliferation MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels MeSH
Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor-initiating cells, which also express HCN channels, remain proliferative during HCN inhibition. IMPLICATIONS: Our finding that NSCs can be selectively rescued while cancer cells remain sensitive to the treatment, provide a foundation for reduction of cognitive impairment in children with neurologic cancers.
Central European Institute of Technology Masaryk University Brno Czech Republic
College of Veterinary Medicine Jilin University Changchun Jilin China
Department of Immunology Genetics and Pathology Uppsala University Rudbeck Laboratory Uppsala Sweden
Department of Medicine Karolinska Institutet Huddinge Sweden
Department of Microbiology New York University School of Medicine New York New York
Department of Neuroscience Karolinska Institutet Solna Sweden
Department of Physiology and Pharmacology Karolinska Institutet Stockholm Sweden
Department of Women's and Children's Health Karolinska Institutet Stockholm Sweden
Gladstone Institute of Neurological Disease San Francisco California
Pediatric Oncology Karolinska University Hospital Stockholm Sweden
References provided by Crossref.org
