Hypoxic ventilatory response in rat pups exposed to dietary tryptophan deficiency

Abstract

Since malnutrition during pregnancy can lead to adverse effects on forebrain development, we were interested in effects it may have on the brainstem and cardiorespiratory function. Sprague-Dawley dams were fed either a control or ~45% tryptophan deficient diet prior to mating, during pregnancy and lactation. Using head-out plethysmography, no significant differences were detected in baseline tidal volume (VT), breathing frequency (FR), or ventilation (VE) at any age (P5, P8, P12). We measured the average ventilatory response to hypoxia by exposing pups to 10 alternating episodes of hypoxia (10% O2, 1 min) and room air (5 min). At P5, tryp deficient diet pups exhibited an enhanced VT and VE response to hypoxia when compared to control (P=0.011; P=0.007). At P8, VT responses were similar between both groups, however the FR and VE responses in diet pups were significantly higher than control (P=0.022; P=0.041). No differences were observed between the two groups at P12. Preliminary analysis indicates post-hypoxic long-term ventilatory depression in controls at P5 and ventilatory facilitation at P8, with no similar effect in diet pups. Results suggest that alterations in dietary tryptophan leads to abnormal ventilatory responses to hypoxia during a sensitive period in development which may be relevant to our understanding of SIDS, where brainstem 5-HT abnormalities could lead to disruption of homeostatic responses.