Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/222862
Title: Oxygen matters: Unraveling the role of oxygen in the neuronal response to cisplatin
Author: Crugeiras, Jose
Calls, Aina
Contreras, Estefanía
Alemany, Montse
Navarro, Xavier
J. Yuste, Victor
Casanovas, Oriol
Udina, Esther
Bruna, Jordi
Issue Date: 27-Sep-2024
Publisher: Wiley
Abstract: Background and AimsCell culture is a fundamental experimental tool for understanding cell physiology. However, translating these findings to in vivo settings has proven challenging. Replicating donor tissue conditions, including oxygen levels, is crucial for achieving meaningful results. Nevertheless, oxygen culture conditions are often overlooked, particularly in the context of chemotherapy-induced neurotoxicity. MethodsIn this study, we investigated the role of oxygen levels in primary neuronal cultures by comparing neuronal performance under cisplatin exposure (1 mu g/mL) in supraphysiological normoxia (representing atmospheric conditions in a standard incubator; 18.5% O2) and physioxia (representing physiologic oxygen conditions in nervous tissue; 5% O2). Experiments were also conducted to assess survival, neurite development, senescence marker expression, and proinflammatory cytokine secretion. ResultsUnder control conditions, both oxygen concentration conditions exhibited similar behaviors. However, after cisplatin administration, sensory neurons cultured under supraphysiological normoxic conditions show higher mortality, exhibit an evolutionarily proinflammatory cytokine profile over time, and activate apoptotic-regulated neuron death markers. In contrast, under physiological conditions, neurons treated with cisplatin exhibited senescence marker expression and an attenuated inflammatory secretome. InterpretationThese results underscore the critical role of oxygen in neuronal culture, particularly in studying compounds where neuronal damage is mechanistically linked to oxidative stress. Even at identical doses of evaluated neurotoxic drugs, distinct cellular phenotypic fates can emerge, impacting translatability to the in vivo setting.
Note: Reproducció del document publicat a: https://doi.org/10.1111/jns.12659
It is part of: Journal of the Peripheral Nervous System, 2024, vol. 29, issue. 4, p. 528-536
URI: https://hdl.handle.net/2445/222862
Related resource: https://doi.org/10.1111/jns.12659
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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