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Articles 1 - 9 of 9
Full-Text Articles in Molecular and Cellular Neuroscience
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Illuminating Transfer Rna Variants As Genetic Modifiers In Models Of Human Disease, Jeremy T. Lant
Electronic Thesis and Dissertation Repository
Transfer RNAs (tRNAs) physically link the genetic code to an amino acid sequence, by recruiting amino acids to three-nucleotide codons in messenger RNAs. To ensure that the genetic code is translated as intended, tRNAs must be accurately aminoacylated and faithfully recognize codons in the ribosome during protein synthesis. Given the critical function of tRNAs, it has often been assumed that mutations in human tRNA genes would be either lethal to cells or not significantly impair tRNA function. My goal was to rigorously test this assumption in mammalian cell models, prompted by the recent discovery of unprecedented variation in human tRNA …
Dnajc7, A Molecular Chaperone Protein That Modulates Protein Misfolding In Amyotrophic Lateral Sclerosis (Als), Meaghan Kathleen Stoltz
Dnajc7, A Molecular Chaperone Protein That Modulates Protein Misfolding In Amyotrophic Lateral Sclerosis (Als), Meaghan Kathleen Stoltz
Electronic Thesis and Dissertation Repository
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease associated with protein misfolding and dysregulated cellular protein quality control mechanisms. Molecular chaperones, and heat shock proteins (Hsp), are key players in maintaining cellular protein quality control. DNAJC7 is an understudied cytosolic Hsp40 that works together with Hsp70 and Hsp90 to regulate proper protein folding or degradation. Of note, mutations in the gene encoding DNAJC7 were discovered to cause familial ALS. We asked whether ALS-associated mutations in DNAJC7 compromise its function as a chaperone, which may cause the toxic accumulation of misfolded proteins. This study attempts to uncover the functions of DNAJC7 …
Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon
Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon
Electronic Thesis and Dissertation Repository
Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming neurons of …
Characterizing The Cognitive And Emotional Effects Of Delta-9-Tetrahydrocannabinol In Distinct Hippocampal Sub-Regions, Dinat Khan
Electronic Thesis and Dissertation Repository
The objective of this study is to determine the potential differential effects of THC in the DH or VH sub-regions, as well as the upstream effects on PFC neuronal activity and oscillations. Rodents used for electrophysiology were infused with THC or vehicle in the DH or VH regions, combined with PFC recordings. Additionally, a battery of behavioural paradigms was performed. Deficits in short-term memory when THC was infused into both regions was observed, however working memory was impaired with VH infusions only. This could be due to THC-induced dysregulation in the PFC, as beta oscillations were significantly decreased selectively in …
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Cerebral Lactate Metabolism And Memory: Implications For Alzheimer's Disease, Richard Andrew Harris
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by amyloid plaques that are comprised of aggregated amyloid-beta peptides. These toxic proteins promote mitochondrial dysfunction and neuronal cell death. A shift in metabolism away from oxidative phosphorylation and toward aerobic glycolysis, with the concomitant production of lactate, affords neurons a survival advantage against amyloid-beta toxicity. Recent evidence now suggests that aerobic glycolysis in the brain plays a critical role in supporting synaptic plasticity, learning, and memory. However, the role of aerobic glycolysis and lactate metabolism in AD-mediated cognitive decline is unknown. My objective was to test the hypotheses that aerobic glycolysis …
Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad
Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, Maha Mahmoud Hammad
Electronic Thesis and Dissertation Repository
PDZ (PSD95/Disc Large/Zona Occludens) domain-containing proteins are scaffolding proteins that play important roles in regulating the activity of G protein-coupled receptors. Corticotropin Releasing Factor Receptor 1 (CRFR1) and Serotonin 2A Receptor (5-HT2AR) are two GPCRs that are commonly associated with mental disorders. Both receptors also contain a class I PDZ-binding motif at the carboxyl terminal tail. In the first chapter, we investigate the effects of CAL (CFTR-associated ligand) on regulating the trafficking and signaling of CRFR1. We demonstrate a role for CAL in inhibiting CRFR1 endocytosis, cell surface expression, and CRF-mediated ERK1/2 signaling via the CRFR1 PDZ-binding motif. …
Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu
Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu
Electronic Thesis and Dissertation Repository
Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrPC) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrPC, α7nAChR, and ALK2 prior to oxygen-glucose deprivation …
Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington
Amyloid Beta Resistance And The Warburg Effect: Re-Examining Alzheimer's Disease, Jordan Taylor Newington
Electronic Thesis and Dissertation Repository
Alzheimer’s disease (AD) is characterized by deposition of the amyloid beta (Ab) peptide in the brain, an event which frequently but not universally correlates with nerve cell death. Although most nerve cells die in response to Ab, small populations of cells are able to survive by becoming resistant to Ab toxicity. Understanding the mechanisms by which cells become resistant to Ab may reveal novel treatments for AD. Interestingly, nerve cell lines selected for resistance against Ab exhibit increased glucose uptake and glycolytic flux. Here I show that these metabolic changes are mediated through an upregulation of pyruvate dehydrogenase kinase 1 …
Characterization Of The Circadian Properties Of Runt-Related Transcription Factor 2 (Runx2) And Its Role In The Suprachiasmatic Nucleus, Meghan E. Reale
Characterization Of The Circadian Properties Of Runt-Related Transcription Factor 2 (Runx2) And Its Role In The Suprachiasmatic Nucleus, Meghan E. Reale
Electronic Thesis and Dissertation Repository
Circadian rhythms orchestrate physiological, behavioral and cognitive processes in order to anticipate and adapt organisms to key environmental cues. These endogenously driven oscillations are generated by a network of interlocked auto-regulatory transcriptional-translational feedback loops driven forward by the Bmal1/Clock heterodimer transcription factor. Given the ubiquitous and dynamic quality of circadian rhythms, the identification of factors involved in the coordination and regulation of the endogenous oscillations is central in broadening our understanding of biological timing systems. In an examination of gene expression in the mammalian central circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), revealed a previously unreported rhythmic expression of runt-related …