Carotid body denervation effect on cytochrome oxidase activity in pre-Bötzinger complex of developing rats

Previously, we found that the rat pre-Bötzinger complex (PBC) exhibited reduced cytochrome oxidase (CO) activity on postnatal days (P) 3–4 and especially on P12, with a concomitant decrease in glutamate and N-methyl-d-aspartate receptor subunit 1, and an increase in GABA, GABAB, glycine recptor, and glutamate subunit 2. We hypothesized that the PBC would be more affected by carotid body denervation (CBD) during the two critical windows than at other times. Pairs of CBD and sham animals at each postnatal day from P2 to P14 and at P21 were operated on and survived for 3 days. Brain stems were processed for CO and neurokinin-1 receptor for the identification of PBC. Results indicate that CBD caused a significant loss in body weight in all animals and a reduction in PBC somal size when the surgery was between P2 and P7. CBD also induced a significant decrease in CO activity of the PBC in most animals and a distinct delay, as well as prolongation of the maturational process, especially when induced close to P3 and P11–P13.

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Postnatal expression of neurotransmitters, receptors, and cytochrome oxidase in the rat pre-Bötzinger complex

Journal of Applied Physiology ◽

10.1152/japplphysiol.00977.2001 ◽

2002 ◽

Vol 92 (3) ◽

pp. 923-934 ◽

Cited By ~ 54

Author(s):

Qiuli Liu ◽

Margaret T. T. Wong-Riley

Keyword(s):

Cytochrome Oxidase ◽

Glycine Receptor ◽

Receptor Subunit ◽

Critical Periods ◽

Time Intervals ◽

General Increase ◽

Respiratory Rhythmogenesis ◽

Aspartate Receptor ◽

Bötzinger Complex ◽

Excitatory Drive

The pre-Bötzinger complex (PBC) is postulated as the center of respiratory rhythmogenesis. Previously, we found a reduction or plateau of cytochrome oxidase (CO) activity in the PBC and other respiratory nuclei at postnatal days 3–4, despite a general increase of CO with age, suggesting a period of synaptic readjustment. The present study examined the expression of CO and a number of neurochemicals in the PBC at closer time intervals. At postnatal days 3–4 and, more prominently, at postnatal day 12, expression of CO, glutamate, and N-methyl-d-aspartate receptor subunit 1 was reduced, whereas expression of GABA, GABABreceptor, glycine receptor, and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor subunit 2 was increased. These findings are consistent with our hypothesis that decreased CO activity is associated with an increase in inhibitory drive (mediated by GABA and glycine, their receptors, and possibly blockage of Ca2+ entry by glutamate receptor subunit 2) and a decrease in excitatory drive (mediated by glutamate and its receptors). Our findings point to two critical periods during postnatal development of the rat when their respiratory system may be more vulnerable to respiratory insults.

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Neurochemical organization of the macaque striate cortex: Correlation of cytochrome oxidase with Na+K+ATPase, NADPH-diaphorase, nitric oxide synthase, and N-methyl-d-aspartate receptor subunit 1

Neuroscience ◽

10.1016/s0306-4522(97)00432-6 ◽

1998 ◽

Vol 83 (4) ◽

pp. 1025-1045 ◽

Cited By ~ 41

Author(s):

M Wong-Riley ◽

B Anderson ◽

W Liebl ◽

Z Huang

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Synthase ◽

Cytochrome Oxidase ◽

Striate Cortex ◽

Nadph Diaphorase ◽

Receptor Subunit ◽

Aspartate Receptor ◽

Oxide Synthase

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Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

Journal of Applied Physiology ◽

10.1152/japplphysiol.00293.2013 ◽

2013 ◽

Vol 115 (7) ◽

pp. 1088-1098 ◽

Cited By ~ 12

Author(s):

Justin Robert Miller ◽

Suzanne Neumueller ◽

Clarissa Muere ◽

Samantha Olesiak ◽

Lawrence Pan ◽

...

Keyword(s):

Carotid Body ◽

Tryptophan Hydroxylase ◽

Inhibitory Neurotransmitters ◽

Carotid Bodies ◽

Respiratory Network ◽

Highly Sensitive ◽

Bötzinger Complex ◽

Chronic Use ◽

A Current ◽

Carotid Body Denervation

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 ΔV̇E/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.

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Plasticity of cardiovascular chemoreflexes after prolonged unilateral carotid body denervation: implications for its therapeutic use

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00451.2019 ◽

2020 ◽

Vol 318 (5) ◽

pp. H1325-H1336

Author(s):

Jaime Eugenín ◽

Carolina Larraín ◽

Patricio Zapata

Keyword(s):

Carotid Body ◽

Therapeutic Use ◽

Therapeutic Effectiveness ◽

Sympathetic Outflow ◽

Sympathetic Hyperactivity ◽

Functional Changes ◽

Human Disorders ◽

Carotid Body Denervation

Unilateral carotid body denervation has been proposed as treatment for sympathetic hyperactivity-related human disorders. Its therapeutic effectiveness for maintaining a persistent decrease in the sympathetic outflow activity will depend on the absence of compensatory chemoreflex plasticity in the remnant carotid and aortic afferents. Here, we suggest that the integrity of central afferents after carotid body denervation is essential to prevent the emergence of plastic functional changes on the contralateral “intact” carotid nerve.

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