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Jan Mennigen Posted by Jan on Wednesday, September 27, 2006 (EST) The serotonergic system in the neuroendocrine brain of Carassius auratus and its disruption by SSRI pharmaceuticals I study the effects of the neurotransmitter serotonin on gene expression in the neuroendocrine brain of goldfish, Carassius auratus. Serotonin is involved in key physiological processes, such as reproduction and food intake, both of which are well characterized in goldfish. Understanding the role serotonin plays with regard to these systems in fish will provide comparative data to mammalian studies and investigate evolutionary conservation of these physiological systems. Establishing the role of serotonin in a model cyprinid fish species is of interest, as several contaminants found in aquatic environments target the serotonergic system, among them ammonia, polychlorinated biphenyls (PCB), heavy metals and selective serotonin reuptake inhibitor (SSRI) pharmaceuticals, the latter of which are specifically designed to target the serotonergic system. In recent experiments, I investigated serotonergic pathways in the goldfish brain with respect to reproduction and feeding. Several candidate genes were identified and were shown to be modulated by fluoxetine, an SSRI and active ingredient of the antidepressent Prozac™. Fluoxetine is used as a model compound in several labs across Ontario in order to investigate the potential impact of SSRIs on fish, of which several have been found in the Great Lakes and recently the St. Lawrence River. Furthermore bioconcentration of fluoxetine and additional SSRIs in the brain and liver of wild fish was also reported. My contribution is the research of molecular mechanisms in the neuroendocrine brain, potentially providing markers that will contribute to detection of subtoxic effects.Techniques I use to study molecular mechanisms in vivo and in vitro include microarray analysis, realtime RT-PCR, as well as radioimmunoassays to measure circulating hormone levels. With regard to reproduction, one target I identified to be affected by SSRIs in female goldfish is the reproductive hormone isotocin, which correlated with a decrease in circulating estradiol. Additional experiments showed that isotocin has stimulatory effects on circulating estradiol levels in female goldfish, and may therefore be partially responsible for the disrupting effect of fluoxetine on circulating estradiol levels. These findings lead to additional experiments, including immunohistochemistry and in vivo and in vitro exposures to further investigate the impact of isotocin on reproduction in fish. With regard to food intake, two neuropeptide genes with known anorectic actions were induced in the neuroendocrine brain of female goldfish exposed to fluoxetine, among them the corticotropin releasing factor (CRF) and the cocaine and amphetamine regulated transcript (CART). I am currently investigating the identified targets by using exposures of different fluoxetine doses, including environmentally relevant levels. Results from these studies will provide information on potential subtoxic effects of fluoxetine on key serotonergic pathways modulating reproduction and food-intake in fish. Notify me when a new comment is posted Add Your Comment