Author ORCID Identifier

https://orcid.org/0000-0001-7165-5467

Year of Publication

2018

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Agriculture, Food and Environment

Department

Veterinary Science

First Advisor

Dr. Amanda A. Adams

Abstract

Consumption of endophyte-infected (E+) grasses has long been associated with health problems in animals. In cattle E+ tall fescue consumption leads to fescue toxicosis, and in horses it leads reproductive problems. The health-related issues associated with endophyte consumption have been attributed to the effects caused by the ergot alkaloids produced by the fungus. These ergot alkaloids are considered D2-like receptor agonists, and 5-HT2 serotonin and α-adrenergic receptor partial agonists. Many studies in humans, swine, cattle, and horses have identified that ergopeptines cause a decrease in prolactin production due to their dopaminergic activities. Additionally, these molecules have been found to cause vasoconstriction in cattle and horses through their other agonistic activities. Furthermore, dopamine agonists are currently being used to treat pituitary pars intermedia dysfunction (PPID) in horses, a condition in which the horse lacks sufficient dopamine. However, the ergot alkaloids found in E+ tall fescue had not previously been investigated for their potential benefits in treating PPID horses. Moreover, little research has investigated the effects of ergot alkaloids and dopamine agonists on the immune system of horses, even though many health problems associated with E+ tall fescue consumption suggest there to be an elicited inflammatory response. Thus, the primary objective of this study was to establish an understanding of immune and hormone responses to ergot alkaloids and dopamine agonists in the horse. The hypothesis of this body of research was that ergot alkaloids and bromocriptine both would elicit inflammatory and hormone responses in the horse. Specifically, this research was conducted to determine the effects of E+ tall fescue seed consumption on immune, hormone, and vasoconstrictive responses, in both non-PPID and PPID horses. In addition, both the in vitro and in vivo effects of bromocriptine on cytokine production from equine peripheral blood mononuclear cells (PBMCs) were investigated. In the first study, there were no significant changes in body morphometrics, vasoconstriction, hormone responses or cytokine expression due to the consumption of ergot alkaloids in non-PPID and PPID horses. The second study was an in vitrostudy in which PBMCs were exposed to varying concentrations of either bromocriptine, a D2-like receptor agonist that is used as a model for ergot alkaloid consumption, or dopamine. This experiment demonstrated that exposure to dopamine or a dopamine agonist at a concentration greater than 10-5M is toxic to PBMCs, and that bromocriptine elicits an anti-inflammatory effect at concentrations less than 10-5M. Concentrations of dopamine less than 10-5M, on the other hand, did not cause any significant changes in cytokine expression. A third study was conducted that evaluated the effects of an intravenous injection of bromocriptine on hormone and immune responses in the aged mare. This study identified that bromocriptine maximally reduced prolactin levels 12 hours post-injection and prolactin returned to baseline levels approximately 56 hours post-injection. Additionally, only a significant increase in IL-1β was detected 12 hours post-injection, which suggests bromocriptine was activating an innate immune response. Overall, the body weights and rectal temperatures of horses did not significantly change in any of the experiments, which indicated that aged non-pregnant horses are able to tolerate E+ tall fescue. In addition, this body of research identified that intravenous delivery of a semi-synthetic dopamine agonist, bromocriptine, and not an oral delivery of an E+ tall fescue seed derived dopamine agonist, caused a decrease in prolactin concentrations, but revealed conflicting results regarding inflammatory responses. In summary, further research is warranted to determine the mechanism of action that dopamine agonists have on the immune system of horses.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2018.375

Funding Information

This research was supported by the USDA/ARS [grant number 3210000244].

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