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Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats
Author(s) -
Burgraff Nicholas J.,
Neumueller Suzanne E.,
Buchholz Kirstyn J.,
LeClaire John,
Hodges Matthew R.,
Pan Lawrence,
Forster Hubert V.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901288rr
Subject(s) - hypercapnia , serotonergic , brainstem , medicine , raphe nuclei , anesthesia , catecholaminergic cell groups , respiratory system , raphe , hyperpnea , endocrinology , catecholaminergic , serotonin , catecholamine , receptor
Despite the prevalence of CO 2 retention in human disease, little is known about the adaptive neurobiological effects of chronic hypercapnia. We have recently shown 30‐d exposure to increased inspired CO 2 (InCO 2 ) leads to a steady‐state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO 2 /H + chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in aminergic and inflammatory signaling during carotid body denervation‐induced hypercapnia, we hypothesized chronic hypercapnia per se will lead to similar changes. We found that: 1 ) increased InCO 2 increased IL‐1β in the medullary raphe (MR), ventral respiratory column, and cuneate nucleus after 24 h, but not after 30 d of hypercapnia; 2 ) the number of serotonergic and total neurons were reduced within the MR and ventrolateral medulla following 30 d of increased InCO 2 ; 3 ) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO 2 ; and 4 ) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO 2 . We conclude that these changes may contribute to initiating or maintaining respiratory neuroplasticity during chronic hypercapnia but alone do not account for ventilatory acclimatization to chronic increased InCO 2 .—Burgraff, N. J., Neumueller, S. E., Buchholz, K. J., LeClaire, J., Hodges, M. R., Pan, L., Forster, H. V. Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats. FASEB J. 33, 14491‐14505 (2019). www.fasebj.org