AUTHOR=Leite Jacqueline Alves , Pôças Elisa , Maia Gisele Silva , Barbosa Leandro , Quintas Luis Eduardo M. , Kawamoto Elisa Mitiko , Silva Maria Luiza Correia da , Scavone Cristoforo , de Carvalho Luciana E. Drumond TITLE=Effect of ouabain on calcium signaling in rodent brain: A systematic review of in vitro studies JOURNAL=Frontiers in Pharmacology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.916312 DOI=10.3389/fphar.2022.916312 ISSN=1663-9812 ABSTRACT=

The Na⁺/K⁺-ATPase is an integral membrane ion pump, essential to maintaining osmotic balance in cells in the presence of cardiotonic steroids; more specifically, ouabain can be an endogenous modulator of the Na⁺/K⁺-ATPase. Here, we conducted a systematic review of the in vitro effects of cardiotonic steroids on Ca²⁺ in the brain of rats and mice. Methods: The review was carried out using the PubMed, Virtual Health Library, and EMBASE databases (between 12 June 2020 and 30 June 2020) and followed the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results: in total, 829 references were identified in the electronic databases; however, only 20 articles were considered, on the basis of the inclusion criteria. The studies demonstrated the effects of ouabain on Ca²⁺ signaling in synaptosomes, brain slices, and cultures of rat and mouse cells. In addition to the well-known cytotoxic effects of high doses of ouabain, resulting from indirect stimulation of the reverse mode of the Na⁺/Ca²⁺ exchanger and increased intracellular Ca²⁺, other effects have been reported. Ouabain-mediated Ca²⁺ signaling was able to act increasing cholinergic, noradrenergic and glutamatergic neurotransmission. Furthermore, ouabain significantly increased intracellular signaling molecules such as InsPs, IP3 and cAMP. Moreover treatment with low doses of ouabain stimulated myelin basic protein synthesis. Ouabain-induced intracellular Ca²⁺ increase may promote the activation of important cell signaling pathways involved in cellular homeostasis and function. Thus, the study of the application of ouabain in low doses being promising for application in neurological diseases.

Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020204498, identifier CRD42020204498.