Parasitic castration of snails by larval trematodes, which manifests itself as histopathological changes in the gonads and/or lowered oviposition, represents one of the most dramatic examples of how parasites are capable of modifying the host's internal environment to favor their own growth and reproduction. However, the molecular basis for this phenomenon is still unknown. Preliminary findings show that Schistosoma mansoni infection of the snail Biomphalaria glabrata leads to a depression in oviposition and concurrently in the levels of several host biogenic amines in the CNS and/or plasma, including L-dopa, dopamine, and serotonin. Since these bioamines regulate reproductive activity in other molluscs, this research proposal addresses the hypothesis that parasitic castration by larval schistosomes is due in part to parasite modulation of snail host bioamine levels or enzymes responsible for their synthesis. Using a combination of analytical methods to quantify bioamine levels and enzyme activities in snail tissues, in vivo inhibition experiments, and assays measuring bioamine interaction with host reproductive organs and larval S. mansoni, the investigator will address four specific aims: 1) to determine the effects of schistosome infection on bioamine levels in the central nervous system (CNS), gonads, albumin gland, and cell-free hemolymph (plasma) of the snail host, B. glabrata, 2) to determine the impact of larval infection on key enzymes involved in bioamine synthetic pathways in the CNS, 3) to assess effects of in vivo and in vitro monoamine manipulations on reproductive activity of infected and noninfected snails, and 4) to assess the ability of larval schistosomes to take up and metabolize, or inhibit activity of, host bioamines. Understanding the role of bioamines in snail reproduction and how parasites interfere with their activity may lead to novel methods of biological control based on metabolic disruption of egg production in the vector snail.
