Consequences of postnatal myo‐inositol supplementation on respiratory control and nucleus tractus solitarius (nTS) neurons

Abstract

Myo‐inositol is a naturally occurring sugar derivative formed endogenously from the breakdown of glucose; it is also found in a variety of foods including breast milk and is commercially available as a nutritional supplement. Serum levels of myo‐inositol in infants decrease naturally over the first few postnatal weeks; prior studies in preterm infants have demonstrated improved pulmonary function, reduced incidence of respiratory distress, and increased survival rates following myo‐inositol supplementation. In support of a potential beneficial effect of myo‐inositol supplementation on respiratory control, we have shown previously that myo‐inositol treatment over the first 2 postnatal weeks enhances the acute hypoxic ventilatory response (HVR). In the present study, we tested the hypothesis that the enhanced HVR following myo‐inositol treatment would be associated with increased excitability of neurons within the area of brainstem chemoafferent integration, the nucleus tractus solitarius (nTS). Mouse pups received subcutaneous injections of myo‐inositol (80 mg/kg/day) for the first two postnatal weeks. Whole cell patch clamp recordings were then used to examine the excitatory properties of nTS neurons monosynaptically connected to the solitary tract. Compared to saline treated mice, myo‐inositol exposure increased the rheobase and the failure rate of nTS neurons, and decreased the paired pulse ratio following 20 Hz stimulation. Spontaneous activity (EPSC frequency, area, rise time, decay time), and basic neuronal properties (membrane resistance, capacitance, resting membrane potential) did not differ between groups. In conclusion, and contrary to our hypothesis, the enhanced HVR following postnatal myo‐inositol treatment was associated with decreased excitability of nTS neurons. We speculate the reduced nTS neuron excitability may be a compensatory response to increased chemoafferent (presumably the carotid body) inputs during hypoxia. These data may be important to our understanding of how myo‐inositol supplementation could influence development and function of brainstem respiratory neural control regions and may have implications for the pathophysiology of various respiratory morbidities in preterm infants.Support or Funding InformationThe Gerber FoundationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.