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Full-Text Articles in Molecular Biology

Methodology To Investigate Protein-Protein Interactions Of Jun During Neuronal Differentiation Of Pc12 Cells, Heather L. Leskinen Dec 2023

Methodology To Investigate Protein-Protein Interactions Of Jun During Neuronal Differentiation Of Pc12 Cells, Heather L. Leskinen

Theses and Dissertations

In humans and other mammals, injury to the central nervous system (CNS) can cause a permanent loss of neuronal function, leading to cognitive defects, limb paralysis, and other neurological disabilities. In contrast, studies have shown that some non-mammalian vertebrates like zebrafish, have the remarkable ability to functionally regenerate axons after CNS injury by reactivating and sustaining the expression of regeneration-associated genes (RAGs). Some RAGs encode transcriptional regulators that dimerize to control downstream gene expression necessary for functional axonal recovery. Our lab has previously identified Jun as an important transcriptional regulator of regeneration after optic nerve injury in zebrafish. After axon …


Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy Jan 2018

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT2A-dependent upregulation of histone deacetylase 2 …


Sex Differences In Differential Fear Conditioning During The Acquisition And Consolidation Of Learned Safety, David Sylvan Reis Aug 2017

Sex Differences In Differential Fear Conditioning During The Acquisition And Consolidation Of Learned Safety, David Sylvan Reis

Theses and Dissertations

The ability to distinguish between threatening and non-threatening situations requires careful regulation of behavioral and physiological responses to stress and fear. Deficits in fear regulation are maladaptive and can lead to the development of anxiety disorders such as PTSD. Women are nearly twice as likely to develop PTSD as are men and laboratory animal studies have shown facilitated fear acquisition, resistance to fear extinction, deficits in extinction retention and impaired discrimination between danger and safety cues in females. Taken together this suggests a propensity for reduced inhibitory control over fear responding in females. Here we investigate the mechanisms underlying fear …


Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan Jan 2017

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 …


Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh Dec 2014

Gene Regulatory Pathways Driving Central Nervous System Regeneration In Zebrafish, Ishwariya Venkatesh

Theses and Dissertations

Damage to the central nervous system (CNS) circuitry of adult mammals results in permanent disability. In contrast, the ability to regenerate damaged CNS nerves and achieve functional recovery occurs naturally in fish. The ability of fish to successfully regrow damaged CNS nerves is in part a consequence of their ability to re-express key neuronal growth-associated genes/proteins in response to CNS injury. On such protein is Growth-Associated Protein-43 (Gap43), a protein which is highly enriched in axonal growth cones during CNS development and regeneration. Experiments conducted in mammals have demonstrated that ectopic expression of GAP-43 improves axonal re-growth after injury. Using …


The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki Dec 2013

The Role Of Gap-43 Phosphorylation In Axon Behavior In The Developing Zebrafish Visual System, Jennifer Forecki

Theses and Dissertations

Developing neurons extend processes to specific targets and establish connections that are essential for future function of the nervous system. One of these processes, the axon, has a motile tip called a growth cone that rearranges its membrane-associated actin cytoskeleton to turn toward or away from environmental guidance cues. Growth associated protein 43 (GAP-43) is one of the most abundant proteins associated with axonal growth cone membranes and is known to modulate the formation and stability of the actin cytoskeleton during axon guidance. Protein kinase C (PKC)-mediated phosphorylation of GAP-43 on serine 42 regulates its interactions with actin. Phosphorylated GAP-43 …