Hyperoxia-induced developmental plasticity of the hypoxic ventilatory response in neonatal rats: Contributions of glutamate-dependent and PDGF-dependent mechanisms

Bavis, Ryan W.; DeAngelis, Kathryn J.; Horowitz, Terry C.; Reedich, Lisa M.; March, Ryan J.

doi:10.1016/j.resp.2013.11.006

Cited by 13 publications

(11 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Current models suggest that postnatal maturation of the HVR (from the immature, biphasic response to the mature, sustained response) involves a shift in the balance of inhibitory and excitatory signaling pathways in the NTS (Gozal et al, 2000). Interestingly, rats reared in hyperoxia exhibit a sustained increase in ventilation during hypoxia (similar to adults) at an earlier age than untreated, control rats (Bavis et al, 2010, 2014a; Hill et al, 2013). Systemic blockade of NMDA glutamate receptors with MK-801 restores the biphasic HVR in hyperoxia-treated rats, suggesting that developmental hyperoxia strengthens glutamatergic signaling through NMDA receptors and/or its downstream signaling pathways (Bavis et al, 2014a); the role of AMPA glutamate receptors was not investigated.…”

Section: Discussionmentioning

confidence: 95%

“…Interestingly, rats reared in hyperoxia exhibit a sustained increase in ventilation during hypoxia (similar to adults) at an earlier age than untreated, control rats (Bavis et al, 2010, 2014a; Hill et al, 2013). Systemic blockade of NMDA glutamate receptors with MK-801 restores the biphasic HVR in hyperoxia-treated rats, suggesting that developmental hyperoxia strengthens glutamatergic signaling through NMDA receptors and/or its downstream signaling pathways (Bavis et al, 2014a); the role of AMPA glutamate receptors was not investigated. At the same time, blockade of inhibitory PDGF-β receptors had no effect on the HVR of hyperoxia-treated rats despite enhancing the HVR of age-matched control rats (Bavis et al, 2014a).…”

Section: Discussionmentioning

confidence: 95%

“…Although cNTS neuron chemosensitivity appeared normal after developmental hyperoxia, there was some evidence for a small decrease in neuronal excitability but enhanced excitatory synaptic input to cNTS neurons within brainstem slices. It is unclear how these small changes interact but the increased network excitability may (partially) compensate for impaired carotid body function and/or contribute to the early maturation of the hypoxic ventilatory response observed in hyperoxia-treated rats (Bavis et al, 2010, 2014a). …”

Section: Discussionmentioning

confidence: 99%

“…Systemic blockade of NMDA glutamate receptors with MK-801 restores the biphasic HVR in hyperoxia-treated rats, suggesting that developmental hyperoxia strengthens glutamatergic signaling through NMDA receptors and/or its downstream signaling pathways (Bavis et al, 2014a); the role of AMPA glutamate receptors was not investigated. At the same time, blockade of inhibitory PDGF-β receptors had no effect on the HVR of hyperoxia-treated rats despite enhancing the HVR of age-matched control rats (Bavis et al, 2014a). It is interesting that this earlier study implicated glutamate signaling through NMDA receptors in hyperoxia-induced plasticity while the present study suggests augmented signaling through AMPA receptors.…”

Section: Discussionmentioning

confidence: 99%

“…Neonatal rats exposed to chronic hyperoxia hypoventilate when returned to room air (Bavis et al, 2010, 2014) and exhibit a progressive blunting of their hypoxic ventilatory response (HVR) over the course of the hyperoxic exposure (Bavis et al, 2010). The blunted HVR is an example of developmental plasticity, defined as a form of phenotypic plasticity that is unique to developing organisms (Bavis and Mitchell, 2008).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Ventilatory and chemoreceptor responses to hypercapnia in neonatal rats chronically exposed to moderate hyperoxia

Bavis

DeAngelis

et al. 2017

Respiratory Physiology & Neurobiology

Self Cite

View full text Add to dashboard Cite

Rats reared in hyperoxia hypoventilate in normoxia and exhibit progressive blunting of the hypoxic ventilatory response, changes which are at least partially attributed to abnormal carotid body development. Since the carotid body also responds to changes in arterial CO2/pH, we tested the hypothesis that developmental hyperoxia would attenuate the hypercapnic ventilatory response (HCVR) of neonatal rats by blunting peripheral and/or central chemoreceptor responses to hypercapnic challenges. Rats were reared in 21% O2 (Control) or 60% O2 (Hyperoxia) until studied at 4, 6–7, or 13–14 days of age. Hyperoxia rats had significantly reduced single-unit carotid chemoafferent responses to 15% CO2 at all ages; CO2 sensitivity recovered within 7 days after return to room air. Hypercapnic responses of CO2-sensitive neurons of the caudal nucleus tractus solitarius (cNTS) were unaffected by chronic hyperoxia, but there was evidence for a small decrease in neuronal excitability. There was also evidence for augmented excitatory synaptic input to cNTS neurons within brainstem slices. Steady-state ventilatory responses to 4% and 8% CO2 were unaffected by developmental hyperoxia in all three age groups, but ventilation increased more slowly during the normocapnia-to-hypercapnia transition in 4-day-old Hyperoxia rats. We conclude that developmental hyperoxia impairs carotid body chemosensitivity to hypercapnia, and this may compromise protective ventilatory reflexes during dynamic respiratory challenges in newborn rats. Impaired carotid body function has less of an impact on the HCVR in older rats, potentially reflecting compensatory plasticity within the CNS.

show abstract