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- ATRX (2)
- Amyotrophic Lateral Sclerosis (2)
- Drosophila melanogaster (2)
- TDP-43 (2)
- Advanced diffusion magnetic resonance imaging (1)
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- Alpha thalassemia mental retardation (1)
- Amyotrophic lateral sclerosis (1)
- Arterial Spin Labelling (ASL) (1)
- Astrocyte morphology (1)
- Astrocytes (1)
- BRAIN PLASTICITY (1)
- Brain aging (1)
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- Cerebral Blood Flow (CBF) (1)
- Cervical spondylotic myelopathy (1)
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- Concussion (1)
- Connexin (1)
- Cx50 (1)
- ENVIRONMENTAL ENRICHMENT (1)
- Endocytosis (1)
- Epigenetics (1)
- FETAL ALCOHOL SPECTRUM DISORDERS (1)
- FUS (1)
- Frontotemporal Dementia (FTD) (1)
- Gap junction channel (1)
- Gene regulation (1)
- Glycosylation (1)
- Huntington's disease (1)
- IGF-1 (1)
Articles 1 - 12 of 12
Full-Text Articles in Neuroscience and Neurobiology
Microstructural Mri Evolution During Adult Mouse Brain Maturation And Concussion Recovery, Naila Rahman
Microstructural Mri Evolution During Adult Mouse Brain Maturation And Concussion Recovery, Naila Rahman
Electronic Thesis and Dissertation Repository
Mild traumatic brain injury (mTBI), also called concussion, has become a significant public health concern. Current clinical neuroimaging techniques lack the sensitivity and specificity required to reliably detect signs of concussion, as large-scale changes are absent. Diffusion magnetic resonance imaging (dMRI) has arguably had the greatest influence to-date of neuroimaging modalities in mTBI, but previous studies have reported inconsistent findings, as standard dMRI lacks specificity and provides a limited model of neuroanatomy. This thesis explores the application of microstructural MR methods, that go beyond standard dMRI to improve sensitivity and specificity, to a preclinical model of mTBI and adult brain …
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 …
Validation Of Arterial Spin Labeling For Longitudinal Monitoring And Differential Diagnosis Of Frontotemporal Dementia, Tracy Ssali
Electronic Thesis and Dissertation Repository
Frontotemporal dementia (FTD) is a devastating neurodegenerative disease characterized by a rapid decline in behavioural, language, and motor abilities. Advances in the understanding of FTD genetics and pathophysiology, and the subsequent development of novel disease modifying treatments have highlighted the need for tools to assess their efficacy. While structural magnetic resonance imaging (MRI) and functional imaging with 18F-flurodeoxyglucose (FDG) positron emission tomography (PET) are used for clinical diagnosis, structural changes are subtle at the early stages and PET imaging is expensive and access limited. Given the coupling of cerebral blood flow (CBF) to energy metabolism, an attractive alternative is …
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 …
The Role Of The Leucine-Rich (Leur) Domain Of Rho Guanine Nucleotide Exchange Factor (Rgnef) In The Regulation Of Amyotrophic Lateral Sclerosis (Als) Associated Protein Tar Dna-Binding Protein Of 43 Kda (Tdp-43), Hind Amzil
Electronic Thesis and Dissertation Repository
The presence of neuronal cytoplasmic inclusions (NCIs) composed of RNA-binding proteins (RBPs) and neurofilaments is considered to be ALS’s neuropathological hallmark. RGNEF has been previously shown to interact with TDP-43 and to have a regulatory effect on the expression levels of NEFL mRNA and NFL protein in vitro. Here, I examined the mechanism of the RGNEF N-terminus, leucine-rich domain (LeuR) domain’s interaction with TDP-43. I observed that the minimal domain required is 110 amino acids (LeuR110), that the Ankyrin domain adjacent to LeuR110 does not participate, and that LeuR110 forms of a high molecular weight complex with TDP-43 in …
Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland
Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland
Electronic Thesis and Dissertation Repository
ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in AtrxFoxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …
The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun
The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun
Electronic Thesis and Dissertation Repository
Gene transcription required for long-term memory requires the modification of histones. However, there are still many uncertainties about the identity and spatial expression of genes regulated by histone modifications during memory related processes. In this project I examined the role of Drosophila melanogaster methyltransferases Set1 and trx in courtship memory. Genetic knockdown of Set1 and trx in the mushroom body (MB) revealed that Set1 was necessary for short- and long-term memory, while trx was only required for long-term memory. Transcriptional profiling of MBs following trx-knockdown revealed expression changes in MB-enriched genes and genes involved in RNA processing. Among the …
Investigating The Cortical, Metabolic And Behavioral Effects Of Transcranial Direct Current Stimulation In Preparation For Combined Rehabilitation, Kayla N. Ryan
Electronic Thesis and Dissertation Repository
The goal of this thesis was to determine the cortical reorganization that occurs in patients with cervical spondylotic myelopathy (CSM) after surgical decompression and to implement this knowledge into a new rehabilitation strategy. Transcranial direct current stimulation (tDCS) is a non-invasive technique to modulate human behavior. Due to the novel electrode montage used, it was first pertinent that we determine how tDCS would modulate cortical, metabolic and motor behavior in healthy individuals.
We observed the longitudinal functional adaptations that occur in patients with CSM using functional MRI. Enhanced excitation of supplementary motor area (SMA) was observed following surgical decompression and …
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque
Electronic Thesis and Dissertation Repository
Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …
Pore-Lining Residues And Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance, Mary Grace M. Tejada
Pore-Lining Residues And Intracellular Magnesium Concentration Influence Connexin50 Gap Junction Unitary Channel Conductance, Mary Grace M. Tejada
Electronic Thesis and Dissertation Repository
Gap junction (GJ) channels mediate direct intercellular communication. Each GJ channel consists of two hemichannels and each hemichannel is a hexamer of connexins. GJs formed by different connexins display different unitary channel conductance (γj) and intracellular magnesium modulation. The underlying mechanisms are not fully clear. The present study investigates the effect of mutating putative pore-lining residues (G8, G46, and V53 individually or together) into glutamate in Cx50 on homotypic GJ channel properties. Expression of the triple and individual mutants in GJ-deficient N2A cells resulted in the formation of functional GJ channels similar to that of Cx50 GJs. However, …
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. …
Examining The Role Of Atrx In Astrocytes, Haley Mcconkey
Examining The Role Of Atrx In Astrocytes, Haley Mcconkey
Electronic Thesis and Dissertation Repository
Astrocytes perform many homeostatic roles in the brain while supplying metabolites to neurons and mediating synaptic transmission. The current study explored a possible role of the Atrx gene in astrocytes. Hypomorphic mutations in this gene cause the ATR-X intellectual disability syndrome. Deletion of Atrx in the forebrain leads to an apparent increase in reactive astrocytes, potentially caused by the high level of neuroprogenitor cell death. To avoid such non cell-autonomous effects on astrocytes, we generated mice with inducible conditional inactivation of Atrx in astrocytes. Preliminary analysis two weeks following induction of Atrx gene deletion revealed variably lower expression of Connexin …