title: Acute exercise-induced activation of Phox2b-expressing neurons of the retrotrapezoid nucleus in rats may involve the hypothalamus.
abstract: The rat retrotrapezoid nucleus (RTN) contains neurons that have a well-defined phenotype characterized by the presence of vesicular glutamate transporter 2 (VGLUT2) mRNA and a paired-like homeobox 2b (Phox2b)-immunoreactive (ir) nucleus and the absence of tyrosine hydroxylase (TH). These neurons are important to chemoreception. In the present study, we tested the hypothesis that the chemically-coded RTN neurons (ccRTN) (Phox2b(+)/TH(-)) are activated during an acute episode of running exercise. Since most RTN neurons are excited by the activation of perifornical and lateral hypothalamus (PeF/LH), a region that regulates breathing during exercise, we also tested the hypothesis that PeF/LH projections to RTN neurons contribute to their activation during acute exercise. In adult male Wistar rats that underwent an acute episode of treadmill exercise, there was a significant increase in c-Fos immunoreactive (c-Fos-ir) in PeF/LH neurons and RTN neurons that were Phox2b(+)TH(-) (p<0.05) compared to rats that did not exercise. Also the retrograde tracer Fluoro-Gold that was injected into RTN was detected in c-Fos-ir PeF/LH (p<0.05). In summary, the ccRTN neurons (Phox2b(+)TH(-)) are excited by running exercise. Thus, ccRTN neurons may contribute to both the chemical drive to breath and the feed-forward control of breathing associated with exercise.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: B F
authors.initials: BF
authors.lastname: Barna
authors.affiliation: Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Takakura
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, 05508-000 São Paulo, SP, Brazil. Electronic address: tmoreira@icb.usp.br.
authors.forename: T S
authors.initials: TS
authors.lastname: Moreira
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D018398:Homeodomain Proteins / Q000378:metabolism*; D007031:Hypothalamus / Q000502:physiology*; D019344:Lactic Acid / Q000097:blood; D008124:Locomotion / Q000502:physiology*; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D056325:Neuronal Tract-Tracers; D009474:Neurons / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013266:Stilbamidines; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D018398:Homeodomain Proteins; C109220:NBPhox protein; D056325:Neuronal Tract-Tracers; D016760:Proto-Oncogene Proteins c-fos; D013266:Stilbamidines; D014157:Transcription Factors; D019344:Lactic Acid
keywords: ANOVA; CPG; DMH; FG; Fluoro-Gold; PAG; PE; PFA; PVH; PeF/LH; Phox2b; RTN; RVLM; TH; VGLUT2; VLM; VMH; analysis of variance; breathing; c-Fos immunoreactive; c-Fos immunoreactivity; c-Fos-ir; ccRTN; central autonomic pathways; central pattern generator; chemically-coded retrotrapezoid nucleus neurons; dorsal medial hypothalamus; exercise; immunoreactive; ir; medulla oblongata; paired-like homeobox 2b; paraformaldehyde; paraventricular nucleus of the hypothalamus; partial pressure of arterial carbon dioxide; partial pressure of arterial oxygen; periaqueductal gray; perifornical and lateral hypothalamus; polyethylene; retrotrapezoid nucleus; rostral ventrolateral medulla; tyrosine hydroxylase; ventrolateral medulla; ventromedial hypothalamus; vesicular glutamate transporter 2