title: Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation.
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.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Justin Robert
authors.initials: JR
authors.lastname: Miller
authors.forename: Suzanne
authors.initials: S
authors.lastname: Neumueller
authors.forename: Clarissa
authors.initials: C
authors.lastname: Muere
authors.forename: Samantha
authors.initials: S
authors.lastname: Olesiak
authors.forename: Lawrence
authors.initials: L
authors.lastname: Pan
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hodges
authors.forename: Hubert V
authors.initials: HV
authors.lastname: Forster
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002344:Carotid Body / Q000378:metabolism / Q000502:physiology*; D002555:Cerebrospinal Fluid / Q000378:metabolism / Q000502:physiology; D002628:Chemoreceptor Cells / Q000378:metabolism / Q000502:physiology; D003714:Denervation / Q000379:methods; D005260:Female; D006041:Goats / Q000378:metabolism / Q000502:physiology*; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D008526:Medulla Oblongata / Q000378:metabolism / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D012018:Reflex / Q000502:physiology; D015656:Respiratory Mechanics / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology*
chemical_list: D018377:Neurotransmitter Agents; D002245:Carbon Dioxide
keywords: breathing; carotid body; neuromodulation