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dc.contributor.authorKao, Patricia Fen_US
dc.date.accessioned2015-08-04T20:27:53Z
dc.date.available2015-08-04T20:27:53Z
dc.date.issued2012
dc.date.submitted2012
dc.identifier.other(ALMA)contemp
dc.identifier.urihttps://hdl.handle.net/2144/12437
dc.descriptionThesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.en_US
dc.description.abstractNeurodegenerative and neuropsychiatric diseases may share molecular regulators implicated in their pathogeneses as the expression of brain derived neurotrophic factor (BDNF) is altered in both. BDNF and its receptor Tyrosine kinase B (TrkB) may influence brain reserve- the ability of the brain to tolerate pathological changes such as those seen in Alzheimer's Disease (AD) before manifesting clinical signs and symptoms. I investigated whether a specifically vulnerable population of human neurons shows a compensatory response to the neuropathological changes of AD and whether that response depends on an upregulation of the BDNF pathway. I observed increased neuronal TrkB expression associated with early AD pathology in cognitively intact Framingham Heart Study subjects when compared to individuals with no neurofibrillary tangles. As BDNF/TrkB signaling affects memory formation and retention through modification of the actin cytoskeleton, I also examined the expression of actin capping protein beta 2 (Capzb2), a marker of actin cytoskeleton reorganization. My data suggest that increased expression of TrkB and Capzb2 accompanies adequate brain reserve in the initial stages of AD pathology. An extensive search for neuropathological changes in BD revealed reduced number of glial cells in the anterior cingulate cortex (BA24). A reduced number of astrocytes and oligodendrocytes is potentially detrimental for neuronal homeostasis. In examining mRNA expression of genes implicated in neuronal protection, BDNF and TrkB, in pyramidal neurons and glia in BA24, I did not find significant differences between BD patients and controls. Because microRNAs (miRNAs) regulate many genes involved in brain functions altered in BD and schizophrenia (SZ), I compared miRNA expression in exosomal extractions from prefrontal cortices of BD, SZ, and controls. Exosomes are secretory/signaling microvesicles that contain miRNA. I found specific miRNAs from exosome-enriched pellets of the prefrontal cortex of cases with neuropsychiatric disorders to be deregulated as compared to controls: miR-29c in BD, and miR-497 in SZ. In BA24 of BD patients, I found miR-149 to be deregulated. These findings may help explain the previously reported neuropathology of BD.en_US
dc.language.isoen_US
dc.publisherBoston Universityen_US
dc.titleIdentifying regulators of brain reserve and neuropathological changes in cognitive and mood disordersen_US
dc.typeThesis/Dissertationen_US
etd.degree.nameDoctor of Philosophyen_US
etd.degree.leveldoctoralen_US
etd.degree.disciplinePathologyen_US
etd.degree.grantorBoston Universityen_US


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