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Molecular and Cellular Neuroscience Commons™
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Articles 1 - 7 of 7
Full-Text Articles in Molecular and Cellular Neuroscience
Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith
Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith
Theses & Dissertations
Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …
Investigating The Role Of Integrin Beta 3 In Dendritic Arborization In The Supragranular Developing Cerebral Cortex, Zachary Logan Holley
Investigating The Role Of Integrin Beta 3 In Dendritic Arborization In The Supragranular Developing Cerebral Cortex, Zachary Logan Holley
Senior Honors Projects, 2010-2019
Integrin subunits have been implicated in axonal and dendritic outgrowth. In particular, a strong positive association has been found between mutations in integrin beta 3 (Itgb3) and autism spectrum disorder, but little is known about neuronal Itgb3 function in vivo. Many forms of autism spectrum disorder are thought to arise from dysfunctional dendritic arborization and synaptic pruning. Global knockout of Itgb3 in mice leads to autistic-like behaviors. Itgb3-/- mice also have reduced callosal volume, a key neuroanatomical correlate of autism. Here, we test the hypothesis that Itgb3 is required for normal dendritic arborization in layer II/III pyramidal …
The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell
The Role Of Ash1l During Human Neurodevelopment, Anna Bagnell
Senior Theses
Autism spectrum disorders (ASD) are associated with defects in neuronal connectivity and are highly heritable. A significant proportion of ASD cases are of complex genetic etiology; complexity which might reflect the impact of gene-environment interactions. However, there is a gap in our understanding of the mechanisms that underlie the gene-environment interaction in autism complex etiology. Genome wide association studies in large ASD cohorts identified high risk variants associated with autism in genes that regulate histone modifications and remodel chromatin. These findings highlight the relevance of chromatin regulatory mechanisms in the pathology of ASD. Changes in Histone H3 methylation have been …
Changes In Synaptic Protein Content And Signaling In A Mouse Model Of Fragile X Syndrome, Kelly Birch, Peter W. Vanderklish Phd
Changes In Synaptic Protein Content And Signaling In A Mouse Model Of Fragile X Syndrome, Kelly Birch, Peter W. Vanderklish Phd
Undergraduate Honors Theses
Fragile X Syndrome--the most common inherited form of intellectual disability--is characterized by low IQ, impaired social interaction, hyperactivity and impulsivity, and abnormal physical traits including an elongated face and protruding ears. Nearly half of all children with Fragile X also meet diagnostic criteria for autism spectrum disorder. Fragile X is caused by a trinucleotide repeat expansion on the X chromosome, leading to silencing of the Fragile X mental retardation gene (FMR1) and thus lack of expression of Fragile X mental retardation protein (FMRP). As a key translational suppressor, FMRP is crucial for normal neural development and synaptic function. The current …
Neurodevelopmental Defects Associated With Gestational Exposure To Low Levels Of Dbp In Mice, Françoise Sidime
Neurodevelopmental Defects Associated With Gestational Exposure To Low Levels Of Dbp In Mice, Françoise Sidime
Dissertations, Theses, and Capstone Projects
The etiology of autism is thought to involve the complex interplay among genetic and environmental factors. Patterns of inheritance suggest an epigenetic component to the development of autism. A variety of environmental risk factors are known to induce epigenetic changes in DNA, affecting many genes including those autism-associated genes (AAG). The plasticizer dibutyl phthalate (DBP; CAS 84-74-2) is a developmental and reproductive toxin that causes a broad range of birth defects resulting in neurological impairments.
To date, although the effect of DBP as an endocrine and a reproductive disruptor are established, there are only few studies that address the effects …
Messenger Rna Transport And Translation Regulated By The 3' Utrs Of Dendritic Mrnas And Abnormal Alternative Splicing Of Neuroligin1 In The Fmr1 Ko Mouse Hippocampus, Tianhui Zhu
Dissertations, Theses, and Capstone Projects
Fragile X Syndrome (FXS) is one of the most commonly inherited mental retardations. It is caused by the loss of functional fragile X mental retardation protein (FMRP). Loss of functional FMRP is the most widespread single-gene cause of autism. The most prominent phenotype of FXS patients is an IQ ranging from 20 to 70. FMRP is an RNA binding protein, widely expressed in almost all tissues and highly expressed in brain. As a RNA binding protein, 85-90 % of FMRP in the brain is associated with polyribosomes. Approximately 4 % of total mRNA is associated with FMRP, which functions in …
Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart
Fatty Acids Increase Neuronal Hypertrophy Of Pten Knockdown Neurons, Catherine J. Fricano, Tyrone Despenza, Paul W. Frazel, Meijie Li, A. James O'Malley, Gary Westbrook, Bryan Luikart
Dartmouth Scholarship
Phosphatase and tensin homolog (Pten) catalyzes the reverse reaction of PI3K by dephosphorylating PIP3 to PIP2. This negatively regulates downstream Akt/mTOR/S6 signaling resulting in decreased cellular growth and proliferation. Co-injection of a lentivirus knocking Pten down with a control lentivirus allows us to compare the effects of Pten knockdown between individual neurons within the same animal. We find that knockdown of Pten results in neuronal hypertrophy by 21 days post-injection. This neuronal hypertrophy is correlated with increased p-S6 and p-mTOR in individual neurons. We used this system to test whether an environmental factor that has been implicated in cellular hypertrophy …