title: Lithium increases proliferation of hippocampal neural stem/progenitor cells and rescues irradiation-induced cell cycle arrest in vitro.
abstract: Radiotherapy in children causes debilitating cognitive decline, partly linked to impaired neurogenesis. Irradiation targets primarily cancer cells but also endogenous neural stem/progenitor cells (NSPCs) leading to cell death or cell cycle arrest. Here we evaluated the effects of lithium on proliferation, cell cycle and DNA damage after irradiation of young NSPCs in vitro.NSPCs were treated with 1 or 3 mM LiCl and we investigated proliferation capacity (neurosphere volume and bromodeoxyuridine (BrdU) incorporation). Using flow cytometry, we analysed apoptosis (annexin V), cell cycle (propidium iodide) and DNA damage (γH2AX) after irradiation (3.5 Gy) of lithium-treated NSPCs.Lithium increased BrdU incorporation and, dose-dependently, the number of cells in replicative phase as well as neurosphere growth. Irradiation induced cell cycle arrest in G1 and G2/M phases. Treatment with 3 mM LiCl was sufficient to increase NSPCs in S phase, boost neurosphere growth and reduce DNA damage. Lithium did not affect the levels of apoptosis, suggesting that it does not rescue NSPCs committed to apoptosis due to accumulated DNA damage.Lithium is a very promising candidate for protection of the juvenile brain from radiotherapy and for its potential to thereby improve the quality of life for those children who survive their cancer.
authors.affiliation: Center for Brain Repair and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Karolinska Institute, Department of Women's and Children's Health, Stockholm, Sweden.
authors.forename: Giulia
authors.initials: G
authors.lastname: Zanni
authors.affiliation: Center for Brain Repair and Rehabilitation, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.|Karolinska Institute, Department of Women's and Children's Health, Stockholm, Sweden.
authors.forename: Elena
authors.initials: E
authors.lastname: Di Martino
authors.affiliation: Karolinska Institute, Department of Physiology and Pharmacology, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Omelyanenko
authors.affiliation: Karolinska Institute, Department of Physiology and Pharmacology, Stockholm, Sweden.|Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
authors.forename: Michael
authors.initials: M
authors.lastname: Andäng
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Delle
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kecke
authors.initials: K
authors.lastname: Elmroth
authors.affiliation: Karolinska Institute, Department of Women's and Children's Health, Stockholm, Sweden.
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003037:Cobalt Radioisotopes; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005434:Flow Cytometry; D005720:Gamma Rays; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D066298:In Vitro Techniques; D018021:Lithium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000528:radiation effects; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects
chemical_list: D003037:Cobalt Radioisotopes; D018021:Lithium Chloride
keywords: apoptosis; hippocampus; lithium; paediatric oncology; radiotherapy