Faculty Collaboration Database

Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation. J Appl Physiol (1985) 2013 Oct 01;115(7):1088-98

Date

07/23/2013

Pubmed ID

23869058

Pubmed Central ID

PMC3798825

DOI

10.1152/japplphysiol.00293.2013

Scopus ID

2-s2.0-84885213330 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

A current and major unanswered question is why the highly sensitive central CO2/H(+) chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔVE/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P < 0.05), and glutamine and dopamine were significantly below pre-CBD levels (P < 0.05). Serotonin, substance P, and epinephrine were variable but not significantly (P > 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase-expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex.

Author List

Miller JR, Neumueller S, Muere C, Olesiak S, Pan L, Hodges MR, Forster HV

Authors

Hubert V. Forster PhD Professor in the Physiology department at Medical College of Wisconsin
Matthew R. Hodges PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Carbon Dioxide
Carotid Body
Cerebrospinal Fluid
Chemoreceptor Cells
Denervation
Female
Goats
Hypercapnia
Medulla Oblongata
Neurotransmitter Agents
Reflex
Respiratory Mechanics
Wakefulness