Key result
Bilateral carotid body denervation in adult goats acutely reduced GluA2 and GluN1 receptor optical density by 15-30% within medullary respiratory nuclei, with significant recovery by 30 days.
Absolute Event Rate: 71.5% vs 100%
p-value: p=0.004
The initial decrease and subsequent partial recovery of GluA2 and GluN1 receptors in the medulla likely contribute to the hypoventilation and partial recovery of the CO2 chemoreflex after carotid body denervation.
Receptor changes may underlie hypoventilation and recovery after denervation; leaves open translation from goats to clinical respiratory disorders.
The mechanisms which contribute to the time-dependent recovery of resting ventilation and the ventilatory CO2 chemoreflex after carotid body denervation (CBD) are poorly understood. Herein we tested the hypothesis that there are time-dependent changes in the expression of specific AMPA, NMDA, and/or neurokinin-1 (NK1R) receptors within respiratory-related brain stem nuclei acutely or chronically after CBD in adult goats. Brain stem tissues were collected acutely (5 days) or chronically (30 days) after sham or bilateral CBD, immunostained with antibodies targeting AMPA (GluA1 or GluA2), NMDA (GluN1), or NK-1 receptors, and optical density (OD) compared. Physiological measurement confirmed categorization of each group and showed ventilatory effects consistent with bilateral CBD (Miller et al. J Appl Physiol 115: 1088-1098, 2013). Acutely after CBD, GluA1 OD was unchanged or slightly increased, but GluA2 and GluN1 OD were reduced 15-30% within the nucleus tractus solitarius (NTS) and in other medullary respiratory nuclei. Chronically after CBD, GluA1 was reduced (P < 0.05) within the caudal NTS and in other nuclei, but there was significant recovery of GluA2 and GluN1 OD. NK1 OD was not significantly different from control after CBD. We conclude that the initial decrease in GluA2 and GluN1 after CBD likely contributes to hypoventilation and the reduced CO2 chemoreflex. The partial recovery of ventilation and the CO2 chemoreflex after CBD parallel a time-dependent return of these receptors to near control levels but likely depend upon additional initiating and maintenance factors for neuroplasticity.
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Miller et al. (2014) studied Carotid body denervation (n=29). Bilateral carotid body denervation vs. Sham surgery or naive controls was evaluated on GluA2 optical density in the caudal nucleus tractus solitarius acutely (5 days) after denervation (expressed as % of control) (p=0.004). Bilateral carotid body denervation in adult goats acutely reduced GluA2 and GluN1 receptor optical density by 15-30% within medullary respiratory nuclei, with significant recovery by 30 days.
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