Cryprosporidium parvum is a coccidian protozoan that colonizes epithelial cells lining respiratory and digestive tracts of animals and humans. Cryptosporidiosis is a well-recognized zoonotic disease infecting primarily neonates and immunocompromised hosts, including human immunodeficiency virus-infected patients. Clinical disease is manifested as a chronic diarrheal illness that is self-limiting in immunocompetent hosts and prolonged and often life-threatening in hosts with compromised immune systems.The lack of a suitable small animal model for screening anti-cryptosporidial drugs and for examining the pathogenicity and immunobiology of chronic cryptosporidiosis was the impetus for this research effort. The objectives of the present study were three-fold: to characterize chronic Cryptosporidium parvum infections in dexamethasone-immunosuppressed mice; evaluate the effects of Cryprosporidium parvum and dexamethasone on B and T lymphocyte proliferation; and determine the effects of the immunomodulator dehydroepiandrosterone on oocyst shedding intensities of mice infected with Cryptosporidium parvum. Adult C57BL/6N mice were immunosuppressed with the synthetic glucocorticoid dexamethasone, then infected with Cryprosporidium parvum (106 oocysts/mouse) investigated for their ability to sustain a four-month chronic infection. Dexamethasone was administered intraperitoneally (125 Jlg/mouse/day) or orally (8 Jlg/ml) in the drinking water ad libitum. Infection chronicity was characterized by evaluating mouse monality, oocyst excretion in the feces, tissue distribution of the parasite, and parasite-induced pathology. A progressive infection with Cryptosporidium parvum occurred in mice immunosuppressed intraperitoneally and orally as long as dexameth sone was administered. Mice receiving dexamethasone given intraperitoneally had a shoner prepatent period and a more consistent, although cyclic, oocyst shedding pattern when compared with mice given dexamethasone orally. Mice given dexamethasone orally exhibited a delayed prepatent period, with a steady increase in oocyst shedding. All mice receiving dexamethasone orally died within three months following oocyst inoculation. Clinical signs included dehydration, icterus, and reduction in spleen and body weights. Clinical signs were more abrupt in mice receiving oral dexamethasone. Parasite colonization involved the entire intestinal tract, including the pyloric ring and Peyer's patches, but was the heaviest in the terminal ileum. Parasites were present in the lungs, gallbladder, and pancreatic ducts. Pathologic abnormalities were isolated to the terminal small intestine and included blunting and fusion of intestinal villi and crypt hyperplasia. Cryptosporidium parvum and dexamethasone administered in vivo reduced B and T lymphocyte responses to the mitogens lipopolysaccharide and concanavalin A. Dehydroepiandrosterone and dehydroepiandrosterone-sulfate resulted in no significant reductions in cryptosporidial activity as determined by oocyst shedding in the feces.

Cryptosporidium parvum is a coccidian protozoan that colonizes epithelial cells lining respiratory and digestive tracts of animals and humans. Cryptosporidiosis is a well-recognized zoonotic disease infecting primarily neonates and immunocompromised hosts, including human immunodeficiency virus-infected patients. Clinical disease is manifested as a chronic diarrheal illness that is self-limiting in immunocompetent hosts and prolonged and often life-threatening in hosts with compromised immune systems. The lack of a suitable small animal model for screening anti-cryptosporidial drugs and for examining the pathogenicity and immunobiology of chronic cryptosporidosis was the impetus for this research effort. The objectives of the present study were three-fold: to characterize chronic Cryptosporidium parvum infections in dexamethasone-immunosuppressed mice; evaluate the effects of Cryptosporidium parvum and dexamethasone on B and T lymphocyte proliferation; and determine the effects of the immunomodulator dehydroepiandrosterone on oocyst shedding intensities of mice infected with Cryptosporidium parvum Adult C57BL/6N mice were immunosuppressed with the synthetic glucocorticoid dexamethasone, then infected with Cryptosporidium parvum (106 oocysts/mouse) and investigated for their ability to sustain a four-month chronic infection. Dexamethasone was administered intraperitoneally (125μ/mouse/day) or orally (8μ/ml) in the drinking water ad libitum. Infection chronicity was characterized by evaluating mouse mortality, oocyst excretion in the feces, tissue distribution of the parasite, and the parasite-induced pathology. A progressive infection with Cryptosporidium parvum occurred in mice immunosuppressed intraperitoneally and orally as long as dexamethsone was administered. Mice receiving dexamethasone given intraperitoneally had a shorter prepatent period and a more consistent, although cyclic, oocyst shedding pattern when compared with mice given dexamethasone orally. Mice given dexamethasone orally exhibited a delayed prepatent period, with a steady increase in oocyst shedding. All mice receiving dexamethasone orally died within three months following oocyst inoculation. Clinical signs included dehydration, icterus, and reduction in spleen and body weights. Clinical signs were more abrupt in mice receiving oral dexamethasone. Parasite colonization involved the entire intestinal tract, including the pyloric ring and Peyer's patches, but was the heaviest in the terminal ileum. Parasites were present in the lungs, gallbladder, and pancreatic ducts. Pathologic abnormalities were isolated to the terminal small intestine and included blunting and fusion of intestinal villi and crypt hyperplasia. Cryptosporidium parvum and dexamethasone administered in vivo reduced B and T lymphocyte responses to the mitogens lipopolysaccharide and concanavalin A. Dehydroepiandrosterone and dehydroepiandrosterone-sulfate resulted in no significant reductions in cryptosporidial activity as determined by oocyst shedding in the feces.

Prenatal stress may increase the risk for depression in offspring and it has been suggested that this could be linked to alterations in tryptophan metabolism, leading to serotonergic changes. Dietary patterns based on the Mediterranean (Med) diet, which includes foods rich in nutrients involved in the tryptophan-serotonin pathway, have been linked to depressive symptom improvements when used as an intervention. This thesis examined, in a mouse model, whether a Med-based diet normalized depressive-like behaviour and changes in the serotonin system in the colon and hippocampus resulting from a repeated physical restraint stressor administered during the second trimester in adult C57BL/6N female and male offspring. The Med-based diet modulated behaviour and hippocampal serotonin receptors primarily in females and changed the enzyme involved in the colonic serotonergic pathway in males. These results suggest that a Med-based diet may help improve behavioural disturbances stemming from prenatal stress in a sex-specific way, perhaps through its actions on the gut-brain serotonin system.