Decreased Number of Brainstem Serotonin (5‐HT) Neurons During Chronic Hypercapnia in Goats

Abstract

Thirty days after carotid body denervation (CBD) in goats, the number of neurons expressing the rate limiting enzyme for serotonin (5‐HT) synthesis (tryptophan hydroxylase, TPH), in the medullary raphe nuclei (MRN) and the ventrolateral medulla (VLM), was 50% of that in control goats (J. Appl. Physiol. 115, 1088–1098, 2013). This difference could be due to loss of carotid afferents per se, or it could be secondary to the CBD induced chronic hypercapnia. The objective of the present study was to assess the effect of hypercapnia per se on TPH expressing neurons in the MRN and VLM. To achieve the objective, we constructed environmental chambers to chronically house and study the effects of chronic hypercapnia in adult goats. Following a room air control period, the goats were exposed to either room air or an elevated inspired CO2 (InCO2) of 6% for 30‐days. After 30 days of hypercapnia, the brainstems were harvested and immunohistochemistry and western blots were used to determine whether chronic hypercapnia altered the number of TPH expressing neurons in the MRN and VLM. We found that there was a nearly 50% decrease (P<0.01) in the number of neurons expressing TPH within both the MRN and VLM. Additionally, there was a decline in the number of total neurons within these nuclei, suggesting that the loss of TPH expressing neurons may be from neuronal death. We conclude that chronic hypercapnia per se has a major impact on the 5‐HT neuromodulatory system which is important in the control of breathing.Support or Funding Information The Department of Veteran Affairs NIH Grant 007852 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.