title: Impaired central respiratory chemoreflex in an experimental genetic model of epilepsy.
abstract: It is recognized that seizures commonly cause apnoea and oxygen desaturation, but there is still a lack in the literature about the respiratory impairments observed ictally and in the post-ictal period. Respiratory disorders may involve changes in serotonergic transmission at the level of the retrotrapezoid nucleus (RTN). In this study, we evaluated breathing activity and the role of serotonergic transmission in the RTN with a rat model of tonic-clonic seizures, the Wistar audiogenic rat (WAR). We conclude that the respiratory impairment in the WAR could be correlated to an overall decrease in the number of neurons located in the respiratory column.
  
  
  
  Respiratory disorders may involve changes in serotonergic neurotransmission at the level of the chemosensitive neurons located in the retrotrapezoid nucleus (RTN). Here, we investigated the central respiratory chemoreflex and the role of serotonergic neurotransmission in the RTN with a rat model of tonic-clonic seizures, the Wistar audiogenic rat (WAR). We found that naive or kindled WARs have reduced resting ventilation and ventilatory response to hypercapnia (7% CO2). The number of chemically coded (Phox2b+/TH-) RTN neurons, as well as the serotonergic innervation to the RTN, was reduced in WARs. We detected that the ventilatory response to serotonin (1 mm, 50 nl) within the RTN region was significantly reduced in WARs. Our results uniquely demonstrated a respiratory impairment in a genetic model of tonic-clonic seizures, the WAR strain. More importantly, we demonstrated an overall decrease in the number of neurons located in the ventral respiratory column (VRC), as well as a reduction in serotonergic neurons in the midline medulla. This is an important step forward to demonstrate marked changes in neuronal activity and breathing impairment in the WAR strain, a genetic model of epilepsy.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, 05508-000, São Paulo, SP, Brazil.
authors.forename: Leonardo T
authors.initials: LT
authors.lastname: Totola
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-000, São Paulo, SP, Brazil.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Takakura
authors.affiliation: Department of Physiology, Ribeirão Preto School of Medicine, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: José Antonio C
authors.initials: JA
authors.lastname: Oliveira
authors.affiliation: Department of Physiology, Ribeirão Preto School of Medicine, University of São Paulo, 14049-900, Ribeirão Preto, SP, Brazil.
authors.forename: Norberto
authors.initials: N
authors.lastname: Garcia-Cairasco
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, 05508-000, São Paulo, SP, Brazil.
authors.forename: Thiago S
authors.initials: TS
authors.lastname: Moreira
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D004195:Disease Models, Animal; D004827:Epilepsy / Q000503:physiopathology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006935:Hypercapnia / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D012018:Reflex / Q000502:physiology; D012119:Respiration; D012701:Serotonin / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C109220:NBPhox protein; D016760:Proto-Oncogene Proteins c-fos; D014157:Transcription Factors; D012701:Serotonin
keywords: brainstem; breathing; chemoreceptor; epilepsy