Gene expression profiles of tissues and cell-lines can be powerful tools for documenting the genetic response to a particular treatment, such as stressors. However, there is a paucity of information on the genetic stress response in the brain. Therefore, we attempted to profile gene expression in the brain of juvenile steelhead trout (Oncorhynchus mykiss) in response to stressors commonly encountered in aquaculture settings and similar to those encountered in hydropower dam mitigation efforts. We subjected fish to a combined out-of-water and low-water stressor totaling three hours. Plasma stress response factors indicate that fish were undergoing a physiological stress response after 3 hours of continuous stressor. We utilized suppression subtractive hybridization to identify cDNA fragments up- or down-regulated in the brain upon completion of the stressor. Forward and reverse subtractions, and sub-cloning of the purified PCR products yielded 59 clones all of which were sequenced. Sequenced cDNA fragments were subjected to BLASTn and BLASTx searches over the course of one year. Fragments fell into the following functional categories: those associated with ATP generation, signal transduction, ion transport, translational machinery, DNA packaging and mobilization, cell structure, and cDNA fragments with cryptic function. Of the 59, 12 were selected for further analysis, and 5 were confirmed to be differentially expressed by northern hybridization. The differentially expressed genes included cytochrome b, NADH dehydrogenase subunit 2, ATPsynthase subunit 6, a cDNA fragment with unknown function, and neuron specific gene 1. Our results present a first attempt to profile gene expression in the brain of fish and demonstrate the power of molecular tools at capturing large amounts of biological information without having to target any one particular gene. A gene expression profile of the brain consequent to stress provides a catalog of responses at a given time point. This catalog can then be used to isolate full-length cDNAs, localize mRNAs in the brain or other tissue, as probes to determine expression patterns and time courses of gene expression in other tissues, and for the quantification of cDNA molecules with real time PCR. / Graduation date: 2003

This thesis examines the behavioral, structural, cellular, and epigenetic changes observed in offspring exposed to different prenatal stressors. A number of questions were answered in this thesis that contribute to a basic understanding of the mechanisms by which early experiences alter long-term outcomes. These include: 1) What epigenetic modifications are associated with prenatal stress? 2) What are the structural and cellular changes in the brains of offspring that correspond to prenatal stress exposure? 3) How do these epigenetic and structural changes manifest as behavioral changes? And 4) What are the consequences of varying the level of prenatal stress?The key findings were that not all prenatal stress is the same. Variations to the intensity and nature of the stress dramatically alter offspring outcomes. Second, prenatal stress produces changes at many levels and these changes can be functionally related. Expression changes were identified in genes involved in altering dendritic morphology, which in turn modifies behaviour. For the first time, a comprehensive examination of brain plasticity occurred following prenatal stress. Additionally, this thesis demonstrated that brain changes related to prenatal stress are age-dependent and sex-dependent. The effects of prenatal stress on the pre-weaning brain are dramatically different than those observed in adulthood. Also, the sex of the offspring significantly influences neuroanatomical and epigenetic modifications. This finding is of critical importance because a majority of prenatal stress research is conducted on male offspring only. Taken together these discoveries emphasize that perturbations to development during the prenatal period produce persistent changes in the structure and functioning of the brain that will influence all subsequent experiences / xx, 201 leaves ; 29 cm

The influence of experience during brain development was investigated on juvenile behavior, adult amphetamine sensitization, and neuronal structural plasticity in rats. Two experiential factors (i.e., tactile stimulation and stress) were studied either before or soon after birth. Early experience feminized social behavior in males; however, only stress enhanced anxiety-like behavior in males. Repeated amphetamine administration resulted in the development and persistence of behavioral sensitization. However, tactile stimulation attenuated the drug-induced behavioral sensitization whereas stress failed to influence the degree of sensitization. Neuroanatomical findings revealed that early experience altered the cortical and subcortical structures. Furthermore, drug exposure reorganized the brain structures involved in addiction but early experience prevented the drug-associated changes. Early adverse experience influences the subsequent exposure to a drug of abuse at anatomical level whereas a favorable experience has an effect both at behavioral and anatomical levels and thus may play a protective role against drug-induced sensitization and addiction. / xii, 263 leaves : ill. ; 29 cm