title: Microglia modulate respiratory rhythm generation and autoresuscitation.
abstract: Inflammation has been linked to the induction of apneas and Sudden Infant Death Syndrome, whereas proinflammatory mediators inhibit breathing when applied peripherally or directly into the CNS. Considering that peripheral inflammation can activate microglia in the CNS and that this cell type can directly release all proinflammatory mediators that modulate breathing, it is likely that microglia can modulate breathing generation. It might do so also in hypoxia, since microglia are sensitive to hypoxia, and peripheral proinflammatory conditions affect gasping generation and autoresuscitation. Here, we tested whether microglial activation or inhibition affected respiratory rhythm generation. By measuring breathing as well as the activity of the respiratory rhythm generator (the preBötzinger complex), we found that several microglial activators or inhibitors, applied intracisternally in vivo or in the recording bath in vitro, affect the generation of the respiratory rhythms both in normoxia and hypoxia. Furthermore, microglial activation with lipopolysaccharide affected the ability of the animals to autoresuscitate after hypoxic conditions, an effect that is blocked when lipopolysaccharide is co-applied with the microglial inhibitor minocycline. Moreover, we found that the modulation of respiratory rhythm generation induced in vitro by microglial inhibitors was reproduced by microglial depletion. In conclusion, our data show that microglia can modulate respiratory rhythm generation and autoresuscitation.
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto De Neurobiología, UNAM Campus Juriquilla, Querétaro, México.
authors.forename: Jonathan-Julio
authors.initials: JJ
authors.lastname: Lorea-Hernández
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto De Neurobiología, UNAM Campus Juriquilla, Querétaro, México.
authors.forename: Teresa
authors.initials: T
authors.lastname: Morales
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto De Neurobiología, UNAM Campus Juriquilla, Querétaro, México.
authors.forename: Ana-Julia
authors.initials: AJ
authors.lastname: Rivera-Angulo
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto De Neurobiología, UNAM Campus Juriquilla, Querétaro, México.
authors.forename: David
authors.initials: D
authors.lastname: Alcantara-Gonzalez
authors.affiliation: Departamento de Neurobiología del Desarrollo y Neurofisiología, Instituto De Neurobiología, UNAM Campus Juriquilla, Querétaro, México.
authors.forename: Fernando
authors.initials: F
authors.lastname: Peña-Ortega
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D063226:Central Pattern Generators / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008070:Lipopolysaccharides; D051379:Mice; D008839:Microelectrodes; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D008911:Minocycline / Q000494:pharmacology; D010507:Periodicity; D010993:Plethysmography, Whole Body; D012119:Respiration / Q000187:drug effects; D046509:Tissue Culture Techniques
chemical_list: D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D008911:Minocycline
keywords: activation; depletion; gasping; hypoxia; inhibition; microglia