326. Award Talk: Physiological and Transcriptomic Effects of Ergot Alkaloids and 5-hydroxytryptophan in Beef Cattle.

Abstract Fescue toxicosis in beef cattle, resulting from consumption of ergot alkaloids (EA) from toxic endophyte-infected tall fescue (TE), decreases circulating serotonin (5-HT), increases vasoconstriction, and impairs thermoregulation. Previous research demonstrated that increasing serotonin after EA exposure relaxes isolated bovine blood vessels, suggesting a novel potential to mitigate physiological disruptions that occur during fescue toxicosis. The objectives of this research were: 1) determine the effects of EA and 5-HTP on dry matter intake (DMI) regulation and feeding behavior, 2) evaluate 5-HTP to mitigate EA-induced vasoconstriction and susceptibility to heat stress, 3) characterize the effects of EA and 5-HTP on gut integrity and systemic inflammation, and 4) identify transcriptomic responses affected by EA and 5-HTP in the hypothalamus, lateral saphenous vein (LSV), and jejunal epithelium. Twenty-four Angus' Holstein steers were used in a randomized complete block design with a 2 x 2 factorial arrangement. Steers were ruminally-dosed with non-toxic endophyte-infected tall fescue seed or TE to provide either 0 or 15 μg EA/kg of body weight (BW). Additionally, steers were ruminally- dosed with either 0 or 3 mg 5-HTP/kg of BW. This resulted in four treatments: control, 5-HTP, EA, EA + 5-HTP. Steers were housed indoors in individual pens, exposed to cyclical temperatures simulating summer conditions (21 °C–32 °C), and fed alfalfa cubes to supply 1.5 times the net energy maintenance requirement for 15 days. Feeding behavior and thermoregulatory measurements were recorded daily. Blood, BW, and caudal artery hemodynamic measurements were collected in 7-d intervals. On d 16, steers were slaughtered to collect visceral weights and tissues for RNA-Seq (hypothalamus, LSV, and small intestine). The study model resulted in four divergent serotonergic phenotypes: 1) the control had undetectable EA with baseline 5- HTP concentrations, 2) 5-HTP had undetectable EA with elevated 5-HTP concentrations, 3) EA had elevated EA with baseline 5-HTP concentrations, 4) EA + 5-HTP had elevated EA with elevated 5-HTP concentrations. This culminated to increased 5-HT with 5-HTP, decreased 5- HT with EA, and a further decrease in 5-HT with EA + 5-HTP relative to control. Ergot alkaloids depressed DMI and disrupted normal feeding behavior, resulting in divergent BW and BW gain, independent of 5-HTP supplementation. Ergot alkaloids increased susceptibility to heat stress and impaired thermoregulation (increased rectal temperature, increased respiration rate, decreased skin temperature). Fifty percent of the EA-induced vasoconstriction was attenuated with 5-HTP and mechanisms of 5-HT receptor-mediated vascular contraction and relaxation were determined. 5-hydroxytryptophan and EA differentially affected small intestinal growth and markers of systemic inflammation. Transcriptomic analysis of the hypothalamus, LSV, and jejunal epithelium provides insight into the molecular mechanisms associated with changes in regulation of feed intake and metabolism, vasoactivity, and gastrointestinal function. Collectively, these findings advance physiological and mechanistic insight into the onset and amelioration of fescue toxicosis by 5-HTP in beef cattle.