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Neonatal ibotenic acid lesions of the ventralhippocampus : the effects of stress on gene expression and apoptosis

dc.contributor.advisorJuorio, Augusto V.en_US
dc.creatorAshe, Paula Carmellaen_US
dc.date.accessioned2004-10-21T00:20:38Zen_US
dc.date.accessioned2013-01-04T05:05:03Z
dc.date.available2000-07-01T08:00:00Zen_US
dc.date.available2013-01-04T05:05:03Z
dc.date.created2000-07en_US
dc.date.issued2000-07-01en_US
dc.date.submittedJuly 2000en_US
dc.description.abstractRecently, it has been suggested that neurodevelopmental abnormalities underlie schizophrenia. However, it has also been suggested that schizophrenia is a neurodegenerative disease as evidenced by a progressive worsening of symptoms over time. Neurodevelopmental abnormalities may, therefore, create a functionally compromised system that is more susceptible to neuronal atrophy and/or death caused by environmental factors such as stress (a known precipitant of acute psychotic episodes and exacerbant of schizophrenia). This hypothesis was tested using the putative neurodevelopmental model of schizophrenia described by Lipska 'et al'. (1993). The effects of neonatal hippocampal lesions on BDNF mRNA and NMDAR1 mRNA, factors involved in development, cell survival and cell communication, were investigated in adult rats following exposure to a physiological stressor. Apoptosis levels were also investigated in these rats to determine if neurodegeneration was present. Results demonstrate that BDNF mRNA was reduced in the prefrontal cortex and hippocampus of lesioned as compared to sham rats. Increased BNDF mRNA resulted from swim stress in both groups, but the increase in lesioned animals was more pronounced than controls. NMDAR1 mRNA was also reduced in the prefrontal cortex and CA3 and CA1 regions of the hippocampus in lesioned versus sham rats. There was an increase, however, in the dentate gyrus of lesioned versus sham rats. Swim stress increased NMDAR1 mRNA in the prefrontal cortex and decreased it in the hippocampus. There was also an increase in apoptosis in lesioned versus sham rats, with no significant increase in response to stress. Reductions in BDNF mRNA in lesioned versus control animals support the hypothesis that neurodevelopmental lesions may result in a system more susceptible to stressors. Reductions in NMDAR1 mRNA are in accordance with the NMDA glutamate receptor hypofunction theory of schizophrenia. It is possible that reductions in glutamate function can remove the inhibitory effect of GABA, thereby resulting in overexcitation of the system and a potential for neurodegeneration. Increased apoptosis supports the presence of neurodegeneration as an ongoing phenomenon. Even though the effect of acute stress on apoptosis was not significant, the very small increases demonstrated can have significant functional consequences over extended periods of time.en_US
dc.identifier.urihttp://hdl.handle.net/10388/etd-10212004-002038en_US
dc.language.isoen_USen_US
dc.subjectschizophreniaen_US
dc.subjectneurodevelopmental abnormalitiesen_US
dc.subjectneuronal viabilityen_US
dc.subjectneuronal communicationen_US
dc.subjectBDNF mRNAen_US
dc.subjectNMDAR1 mRNAen_US
dc.titleNeonatal ibotenic acid lesions of the ventralhippocampus : the effects of stress on gene expression and apoptosisen_US
dc.type.genreThesisen_US
dc.type.materialtexten_US
thesis.degree.departmentPsychiatryen_US
thesis.degree.disciplinePsychiatryen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophy (Ph.D.)en_US

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