Selective Depletion of Astrocytes Derived From a Phox2b‐Progenitor Domain Reduces Hypoxia Ventilatory Response in Conscious Mice

Abstract

The peripheral chemoreceptors stimulate the respiratory pattern generator directly and indirectly by activating retrotrapezoid nucleus (RTN) via a neuronal projection from the nucleus of the solitary tract. The RTN neurons express the transcription factor Phox2b. In addition to neurons, astrocytes from ventral medullary surface appear to contribute to respiratory drive and have a developmental connection with RTN neurons, the aim of this study is determine the extent to which selective ablation of PHOX2B‐derived astrocytes affect ventilation during development. We interbred ALDH1L1loxp‐GFP‐STOP‐loxp‐DTA mice to PHOX2Bcre mice. Breathing variables [tidal volume (VT), respiratory frequency (fR), and minute ventilation (VE)] were measured by whole body unrestrained plethysmography in conscious adult mice. PHOX2B‐derived astrocytes ablation (genotype PHOX2Bcre, ALDH1L1loxp‐GFP‐STOP‐loxp‐DTA) reduces hypoxia (8% O2)‐induced increased in VE (3139.22 ± 250.76, vs. control [genotype ALDH1L1loxp‐GFP‐STOP‐loxp‐DTA] 4194.7 ± 235.16 μl/min/g; p = 0.021; n=6) and VT (13.93 ± 0.6, vs. control 16.53 ± 0.7 μl/g; p = 0.0019; n=6). Our results showed that ablation of PHOX2B‐derived astrocytes produced severely impaired O2 chemosensory response, indicating that these cells may be part of a specialized neural circuitry involved breathing activation.Support or Funding InformationFAPESP and NIHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.