Central neuromodulation and adaptations during respiratory development

primary research S3 lowed by 21% O 2 -79% N 2 for 5 min, either on 6 consecutive days (recurrent episodic hypoxia), or on the 6th day only, following 5 daily normoxic exposures (single episodic hypoxia).Brains were collected either 5 min or 2 h after the last gaseous exposure.Brainstem sections underwent autoradiography with iodinated substance P for NK-1R or DAMGO for MOR.In nucleus tractus solitarius (NTS) from brains collected 2 h after the last exposure, the binding densities of NK-1R and MOR were unaltered by a single episodic hypoxia, and were greatly increased after recurrent episodic hypoxia, indicating an upregulation of both receptors by the recurrent episodic stimulus.In the NTS from the brains collected 5 min after the last hypoxic exposure, there was an important discrepancy in the binding response between the NK-1R and the MOR: The NK-1R displayed a significant decrease in ligand binding after both single and recurrent episodic hypoxia, implying enhanced receptor internalization.In contrast, the binding of MOR was not changed, implying that the rate of receptor internalization was not altered by the hypoxic exposure.This difference would result in relatively greater availability of functional MOR to opioid peptides during hypoxia.At present, we are carrying out the same experiments in developing piglets, using the same hypoxia protocols.If the findings in piglets' brains (to be presented at the Satellite meeting) are the same as those in the adult rat brain, the greater availability of functional MOR as compared to NK-1R during hypoxia may explain the attenuated ventilatory response to repeated hypoxia during development in piglets.

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