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Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.


ABSTRACT: Despite the prevalence of CO2 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 CO2 (InCO2) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO2/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 InCO2 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 InCO2; 3) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO2; and 4) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO2. 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 InCO2.-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.

SUBMITTER: Burgraff NJ 

PROVIDER: S-EPMC6894090 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats.

Burgraff Nicholas J NJ   Neumueller Suzanne E SE   Buchholz Kirstyn J KJ   LeClaire John J   Hodges Matthew R MR   Pan Lawrence L   Forster Hubert V HV  

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20191031 12


Despite the prevalence of CO<sub>2</sub> 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<sub>2</sub> (InCO<sub>2</sub>) leads to a steady-state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO<sub>2</sub>/H<sup>+</sup> chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in ami  ...[more]

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