Some larval parasites alter the behavior of their invertebrate intermediate hosts in ways that enhance the transmission of these parasites to their definitive hosts. In the system considered in this proposal, the cerebral larva of the flatworm Microphallus papillorobustus (Trematoda) changes the responses to mechanical, geotactic, and photic stimuli in Gammarus insensibilis (Crustacea). The resulting aberrant escape behavior renders infected gammarids more susceptible to predation by birds, definitive hosts of the parasite. While the ecological and evolutionary implications of parasitic manipulation have drawn considerable attention, the neural basis of the altered behavior remains largely unknown. It has been established, however, that the ubiquitous neurotransmitter serotonin is involved in the altered responses demonstrated by infected gammarids.
This project focuses on the biochemical events upstream of the serotonergic dysfunction, and addresses the hypothesis that neuroinflammation is involved in the disruption of serotonergic pathways and in the altered responses to environmental stimuli in infected gammarids. Neuroinflammation denotes chronic inflammation-like glial responses of the central nervous system (CNS) that may engender neuropathological events. If this hypothesis is correct, inflammatory factors should be produced and released by glial cells in the brain of M. papillorobustus infected gammarids. Thus, immunocytochemical experiments will be performed to find evidence of inflammatory products such as cytokines and nitric oxide in infected brains. Cytokines are signaling molecules of the immune system that play a central role in CNS inflammatory responses as well as in neurotransmitter modulation. Immunocytochemical techniques will also be used to address the question of the modified architecture of neurons in infected brains. Some undergraduate students will be involved in the project while many others will benefit indirectly in the various research oriented teaching laboratories offered at Wellesley College a liberal arts women institution that recruits students from all socio-economic, national, and ethnic backgrounds.
From an evolutionary standpoint, the exploitation by parasites of phylogenetically conserved host defense mechanisms could explain how manipulation of the host behavior has evolved repeatedly in systems involving different taxonomic groups of parasites and hosts. From a neuropathological point of view, consequences of chronic inflammatory responses have been implicated in numerous brain diseases from Parkinson's, to Alzheimer's, rabies, and neurocysticercosis caused by the cerebral larvae of flatworms. The system M. papillorobustus/G. insensibilis stands to help our understanding of these debilitating conditions as it represents a simple invertebrate model of chronic cerebral parasitic disease. Finally, the topic possesses a definite intrinsic appeal. Examples of sophisticated interspecific interactions abound, but the "alien strategy" perfected by some parasites captures the imagination of scientist and layman alike.
