Changes in Neurochemicals Within the Ventrolateral Medullary Respiratory Column in Awake Goats After Carotid Body Denervation

Authors

Justin Robert Miller, Medical College of Wisconsin
Suzanne E. Neumueller, Medical College of Wisconsin
Clarissa Muere, Medical College of Wisconsin
Samantha Olesiak, Medical College of Wisconsin
Lawrence Pan, Marquette UniversityFollow
Matthew R. Hodges, Medical College of Wisconsin
Hubert V. Forster, Medical College of Wisconsin

Document Type

Article

Language

eng

Format of Original

11 p.

Publication Date

2013

Publisher

American Physiological Society

Source Publication

Journal of Applied Physiology

Source ISSN

0021-8987

Original Item ID

doi: 10.1152/japplphysiol.00293.2013

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 Pa_CO2) and exhibited a reduced CO₂ chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇_E/ΔPa_CO2) 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.

Comments

Accepted version. Journal of Applied Physiology, Vol. 115, No. 7 (October 1st, 2013): 1088-1098. DOI. © 2013 American Physiological Society. Used with permission.

Recommended Citation

Miller, Justin Robert; Neumueller, Suzanne E.; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.; and Forster, Hubert V., "Changes in Neurochemicals Within the Ventrolateral Medullary Respiratory Column in Awake Goats After Carotid Body Denervation" (2013). Physical Therapy Faculty Research and Publications. 53.
https://epublications.marquette.edu/phys_therapy_fac/53