Neotyphodium Toxicoses

Abstract

Our understanding of the etiology of the animal/Neotyphodium interaction has accelerated in the last decade. The urgent need for solutions to these toxicoses, combined with the complexity of this toxicological phenomenon, impels the research community towards the study of mechanisms through which cellular and molecular regulation may be understood and manipulated. The objective of this presentation is to summarize cellular and molecular techniques which are currently employed or have potential application in discovery research or toxicoses therapy in affected animals. Relevant discussions of the animal/Neotyphodium interaction and specifically the physiological effects manifested in domesticated ruminants and laboratory species are discussed by Dr. Jack Oliver within these proceedings. Current animal toxicosis control measures involve reduction, dilution or avoidance of the toxins, essentially through forage and/or diet supplement management. Animal-based toxicoses control strategies which would prevent health and production problems associated with the animal/Neotyphodium interaction need further development. This development is required because it will not be possible to eliminate or modify endophyte infection in many locations and thus animal exposure to Neotyphodium toxins will continue. Finding effective solutions for these animal-based problems demands a thorough biological understanding of the causative toxin(s) and their mode of action. Current and new techniques must be relevant, accurate, precise, and repeatable to achieve research objectives which increase the understanding of these toxicoses. The techniques chosen by researchers should help clarify several critical areas in understanding the animal/Neotyphodium interactions. First, the identification of the responsible toxin(s) and their physiological role is an important goal that has been complicated because multiple members of the major toxin classes are probably involved. Selected techniques must utilize individual toxins or be able to differentiate effects between toxins of the same or different structural classes. These differentiations could include potency of toxins in the same group or the activity of toxins in different groups. Second, scant information exists about the metabolic fates of each toxin and/or the potential physiological role of toxin intermediates. Technique development and validation will be needed to quantify toxins, intermediates, and their effects in the digestive, circulatory and cellular systems. Third, each toxin likely has specific critical circulating threshold concentrations which depend upon the physiological response and ratios of endogenous receptor subtypes within each tissue-bed, organ or anatomical location at which they invoke physiological responses. How these concentrations relate to those obtained after grazing toxic pasture is a key research area which will require a systematic, coordinated approach for success. Fourth, the body of literature does not thoroughly address whether the toxins have independent, additive, synergistic or antagonistic effects and at which concentrations these effects may become important physiologically. When these research objectives are elaborated, prevention and control of the animal/Neotyphodium toxicoses through animal-based methods will be greatly enhanced.