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Full-Text Articles in Life Sciences
Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish
Effects Of A Novel, Non-Toxic Histone Deacetylase Inhibitor On Hippocampal Memory Formation, Histone Acetylation, And Bdnf Gene Expression In Male Mice, Sarah Brianna Beamish
Theses and Dissertations
Memory dysfunction is a common symptom of aging, neuropsychiatric disorders, and neurodegenerative disorders, yet truly effective treatments for memory loss do not exist. De novo gene transcription is a molecular requirement for long-term memory formation. The transcription of genes related to synaptic plasticity and learning are regulated in part by histone acetylation, an epigenetic mechanism that regulates chromatin accessibility. Pharmacological compounds that maintain histone acetylation, called histone deacetylase inhibitors (HDACi), enhance memory by preventing deacetylation of core histone proteins, which initiates binding of transcriptional machinery to open chromatin. Therefore, HDACi are potentially promising therapeutics that could be used to prevent …
Epigenetic Alterations At Synaptic Plasticity Genes In A Genetically Heterogeneous Rat Model Of Neuropsychiatric Disorders, Doan M. On
Theses and Dissertations
Sensorimotor gating impairments are observed across a range of neuropsychiatric conditions. The prepulse inhibition of the acoustic startle response (PPI) is a validated measure of sensorimotor gating. Genetic and pharmacological manipulations in rodents have shown PPI is regulated by specific brain monoaminergic systems. Using genetically heterogeneous NIH-HS rats, we stratified individuals by %PPI. In low PPI animals, we observed elevated mRNA levels of certain neurotransmitter receptors, including metabotropic glutamate receptor Grm2, dopamine receptors Drd1 and Drd2, serotonin receptors Htr1a and Htr2a, and scaffolding protein Homer1, in the frontal cortex (FC) and striatum (STR). We found Drd2 …
Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan
Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan
Theses and Dissertations
DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic …
Methods For Integrative Analysis Of Genomic Data, Paul Manser
Methods For Integrative Analysis Of Genomic Data, Paul Manser
Theses and Dissertations
In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …