Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton
School of Arts & Sciences Theses
Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.
Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, 2016 The University of Western Ontario
Corticotropin Releasing Factor Receptor Type 1 Signaling In Epilepsy And Traumatic Brain Injury, V V Chakravarthi Narla
Electronic Thesis and Dissertation Repository
Stress increases the frequency by which epileptic seizures occur. Corticotropin-releasing factor (CRF) coordinates neuroendocrine, autonomic and behavioral response to stress. This thesis sought to study the cellular and molecular mechanisms by which CRF regulates the activity of neural circuits in the piriform cortex (PC) in normal and epileptic states. The PC is richly innervated by CRF and 5-HT containing axons arising from the central amygdala and raphe nucleus. CRFR1 and 5-HT2A/CRs have been shown to interact in a manner where CRFR activation subsequently potentiates the activity of 5-HT2A/CRs. The first purpose of this ...
Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes And Interaction Networks Involved In The Central Circadian Clock, 2016 Thomas Jefferson University
Single-Cell Transcriptional Analysis Reveals Novel Neuronal Phenotypes And Interaction Networks Involved In The Central Circadian Clock, James Park, Haisun Zhu, Sean O'Sullivan, Babatunde A. Ogunnaike, David R. Weaver, James S. Schwaber, Rajanikanth Vadigepalli
Neurobiology Publications and Presentations
Single-cell heterogeneity confounds efforts to understand how a population of cells organizes into cellular networks that underlie tissue-level function. This complexity is prominent in the mammalian suprachiasmatic nucleus (SCN). Here, individual neurons exhibit a remarkable amount of asynchronous behavior and transcriptional heterogeneity. However, SCN neurons are able to generate precisely coordinated synaptic and molecular outputs that synchronize the body to a common circadian cycle by organizing into cellular networks. To understand this emergent cellular network property, it is important to reconcile single-neuron heterogeneity with network organization. In light of recent studies suggesting that transcriptionally heterogeneous cells organize into distinct cellular ...
Mechanisms Of Synaptic Development And Premature Aging In Drosophila: A Dissertation, 2016 University of Massachusetts Medical School
Mechanisms Of Synaptic Development And Premature Aging In Drosophila: A Dissertation, Yihang Li
GSBS Dissertations and Theses
Development and aging, two fundamental aspects of life, remain key biological processes that researchers try to understand. Drosophila melanogaster, thanks to its various merits, serves as an excellent model to study both of these processes. This thesis includes two parts. In the first part, I discuss our finding that the presynaptic neuron controls a retrograde signaling pathway by releasing essential components via exosomes. During synaptic development, postsynaptic cells send retrograde signals to adjust the activity and growth of presynaptic cells. It remains unclear what the mechanism is which triggers the release of retrograde signals; and how presynaptic cells are involved ...
Voltage-Gated K+ Channels And Hiv-1-Induced Neural Injury: Implications For Pathogenesis Of Hiv-1-Associated Neurocognitive Disorders, 2016 University of Nebraska Medical Center
Voltage-Gated K+ Channels And Hiv-1-Induced Neural Injury: Implications For Pathogenesis Of Hiv-1-Associated Neurocognitive Disorders, Han Liu
Theses & Dissertations
Human immunodeficiency virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is a subcortical disease involving neuronal loss and myelin damage. Myelin is deposited by oligodendrocytes through a complex process including oligodendrocyte progenitor cell (OPC) proliferation and maturation. Oligodendrocytes/OPCs are susceptible to viral proteins such as Tat and that myelin damage is associated with oligodendrocyte number decrease. It has been shown that activation of voltage-gated K+ (KV) channels mediates apoptosis in various cell types. KV1.3 is the most predominant KV channel expressed in OPCs/oligodendrocytes and potentially involved in OPC developmental regulation. We studied the involvement of ...
Cal And Magi Pdz Protein Regulation Of Crfr1 And 5-Ht2ar Trafficking And Signaling, 2016 The University of Western Ontario
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 ...
Insulin-Like Signaling Promotes Glial Phagocytic Clearance Of Degenerating Axons Through Regulation Of Draper, 2016 Oregon Health and Science University
Insulin-Like Signaling Promotes Glial Phagocytic Clearance Of Degenerating Axons Through Regulation Of Draper, Derek T. Musashe, Maria D. Purice, Sean D. Speese, Johnna E. Doherty, Mary A. Logan
Open Access Articles
Neuronal injury triggers robust responses from glial cells, including altered gene expression and enhanced phagocytic activity to ensure prompt removal of damaged neurons. The molecular underpinnings of glial responses to trauma remain unclear. Here, we find that the evolutionarily conserved insulin-like signaling (ILS) pathway promotes glial phagocytic clearance of degenerating axons in adult Drosophila. We find that the insulin-like receptor (InR) and downstream effector Akt1 are acutely activated in local ensheathing glia after axotomy and are required for proper clearance of axonal debris. InR/Akt1 activity, it is also essential for injury-induced activation of STAT92E and its transcriptional target draper ...
Therapeutic Raavrh10 Mediated Sod1 Silencing In Adult Sod1(G93a) Mice And Nonhuman Primates, 2016 University of Massachusetts Medical School
Therapeutic Raavrh10 Mediated Sod1 Silencing In Adult Sod1(G93a) Mice And Nonhuman Primates, Florie Borel, Gwladys Gernoux, Brynn Cardozo, Jake P. Metterville, Gabriela Toro Cabrera, Lina Song, Qin Su, Guang Ping Gao, Mai K. Elmallah, Robert H. Brown Jr., Christian Mueller
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease; survival in ALS is typically 3-5 years. No treatment extends patient survival by more than three months. Approximately 20% of familial ALS and 1-3% of sporadic ALS patients carry a mutation in the gene encoding superoxide dismutase 1 (SOD1). In a transgenic ALS mouse model expressing the mutant SOD1(G93A) protein, silencing the SOD1 gene prolongs survival. One study reports a therapeutic effect of silencing the SOD1 gene in systemically treated adult ALS mice; this was achieved with a short hairpin RNA, a silencing molecule that has raised multiple safety concerns ...
Tnf Signaling During Tissue Damage-Induced Nociceptive Sensitization In Drosophila, 2016 The University of Texas Graduate School of Biomedical Sciences at Houston
Tnf Signaling During Tissue Damage-Induced Nociceptive Sensitization In Drosophila, Juyeon Jo
UT GSBS Dissertations and Theses (Open Access)
Tumor necrosis factor (TNF) signaling is required for inflammatory nociceptive sensitization in both Drosophila and vertebrates. In Drosophila larval model of nociceptive sensitization, UV irradiation in results in epidermal apoptosis and thermal allodynia. TNF/Eiger is produced from dying epidermal cells and acts its receptor in nociceptive sensory neurons to induce thermal allodynia. Inhibition of TNF signaling results in attenuation of nociceptive sensitization whereas epidermal apoptosis still occurs in the absence of TNF. Major gaps in this model are the precise relationship between apoptotic cell death and production of TNF/Eiger, downstream signaling mediators for TNFR/Wengen, and target genes ...
Effects Of Glyceollin On Mrna Expression In The Female Mouse Brain., 2016 University of Louisville
Effects Of Glyceollin On Mrna Expression In The Female Mouse Brain., Sanaya Firdaus Bamji
Electronic Theses and Dissertations
Glyceollins (Glys), produced by soy plants in response to stress, have anti-estrogenic activity in breast and ovarian cancer cell lines in vitro and in vivo. In addition to known anti-estrogenic effects, Glys exhibit mechanisms of action not involving estrogen receptor (ER) signaling. To date, effects of Glys on brain physiology and function are unknown. The purpose of the experiments summarized in this dissertation was to gain an understanding of the effects of Gly on brain-related functions in the female mouse brain through the observation of changes in gene expression. For our initial studies, we treated ovariectomized Swiss Webster (CFW) mice ...
Microglia Contribute To Circuit Defects In Mecp2 Null Mice Independent Of Microglia-Specific Loss Of Mecp2 Expression, 2016 University of Massachusetts Medical School
Microglia Contribute To Circuit Defects In Mecp2 Null Mice Independent Of Microglia-Specific Loss Of Mecp2 Expression, Dorothy P. Schafer, Christopher T. Heller, Georgia Gunner, Molly Heller, Christopher Gordon, Timothy Hammond, Yochai Wolf, Steffen Jung, Beth Stevens
Open Access Articles
Microglia, the resident CNS macrophages, have been implicated in the pathogenesis of Rett Syndrome (RTT), an X-linked neurodevelopmental disorder. However, the mechanism by which microglia contribute to the disorder is unclear and recent data suggest that microglia do not play a causative role. Here, we use the retinogeniculate system to determine if and how microglia contribute to pathogenesis in a RTT mouse model, the Mecp2 null mouse (Mecp2(tm1.1Bird/y)). We demonstrate that microglia contribute to pathogenesis by excessively engulfing, thereby eliminating, presynaptic inputs at end stages of disease ( > /=P56 Mecp2 null mice) concomitant with synapse loss. Furthermore, loss ...
Impaired Neurodevelopment By The Low Complexity Domain Of Cpeb4 Reveals A Convergent Pathway With Neurodegeneration, 2016 University of Massachusetts Medical School
Impaired Neurodevelopment By The Low Complexity Domain Of Cpeb4 Reveals A Convergent Pathway With Neurodegeneration, Jihae Shin, Johnny S. Salameh, Joel D. Richter
Open Access Articles
CPEB4 is an RNA binding protein expressed in neuronal tissues including brain and spinal cord. CPEB4 has two domains: one that is structured for RNA binding and one that is unstructured and low complexity that has no known function. Unstructured low complexity domains (LCDs) in proteins are often found in RNA-binding proteins and have been implicated in motor neuron degenerative diseases such as amyotrophic lateral sclerosis, indicating that these regions mediate normal RNA processing as well as pathological events. While CPEB4 null knockout mice are normal, animals expressing only the CPEB4 LCD are neonatal lethal with impaired mobility that display ...
Encoding Of Saltatory Tactile Velocity In The Adult Orofacial Somatosensory System, 2016 University of Nebraska-Lincoln
Encoding Of Saltatory Tactile Velocity In The Adult Orofacial Somatosensory System, Rebecca Custead
Public Access Theses and Dissertations from the College of Education and Human Sciences
Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement.
High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable ...
Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, 2016 Lawrence University
Activation Of Target Gene Expression In Neurons By The C. Elegans Rfx Transcription Factor, Daf-19, Katherine P. Mueller
Lawrence University Honors Projects
DAF-19, the only RFX transcription factor found in C. elegans, is required for the formation of neuronal sensory cilia. Four isoforms of the DAF-19 protein have been reported, and the m86 nonsense (null) mutation affecting all four isoforms has been shown to prevent cilia formation. Transcriptome analyses employing microarrays of L1 and adult stage worms were completed using RNA from daf-19(m86) worms and an isogenic wild type strain to identify additional putative DAF-19 target genes. Using transcriptional fusions with GFP, we compared the expression patterns of several potential gene targets using fluorescence confocal microscopy. Expression patterns were characterized in ...
Changes In Synaptic Protein Content And Signaling In A Mouse Model Of Fragile X Syndrome, 2016 University of San Diego
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 ...
Npas1+ Pallidal Neurons Target Striatal Projection Neurons, 2016 Northwestern University
Npas1+ Pallidal Neurons Target Striatal Projection Neurons, Savio Chan, Kelly Glajch, Daniel Kelver, Daniel Hegeman, Qiaoling Cui, Harry Xenias, Elizabeth Augustine, Vivian Hernández, Neha Verma '17, Tina Huang, Minmin Luo, Nicholas Justice
Student Publications & Research
Compelling evidence demonstrates the external globus pallidus (GPe) plays a key role in processing sensorimotor information. An anatomical projection from the GPe to the dorsal striatum (dStr) has been described for decades. However, the cellular target and functional impact of this projection remain unknown. Using cell-specific transgenic mice, modern monosynaptic tracing techniques, and optogenetics-based mapping, we discovered that GPe neurons provide inhibitory inputs to direct- and indirect-pathway striatal projection neurons (SPNs). Our results indicate that the GPe input to SPNs arises primarily from Npas1- expressing neurons and is strengthened in a chronic Parkinson’s disease (PD) model. Alterations of the ...
An Initial Analysis Of A Long-Term Ketogenic Diet’S Impact On Motor Behavior, Brain Purine Systems, And Nigral Dopamine Neurons In A New Genetic Rodent Model Of Parkinson’S Disease, 2016 Trinity College
An Initial Analysis Of A Long-Term Ketogenic Diet’S Impact On Motor Behavior, Brain Purine Systems, And Nigral Dopamine Neurons In A New Genetic Rodent Model Of Parkinson’S Disease, Jacob Rubin, William H. Church
Senior Theses and Projects
A growing body of research suggests that dopaminergic cell death seen in Parkinson’s disease is caused by mitochondrial dysfunction. Oxidative stress, with subsequent generation of reactive oxygen species, is the hallmark biochemical product of mitochondrial dysfunction. The ketogenic diet has been found to enhance mitochondrial energy production, protect against reactive oxygen species-generated cell death, and increase adenosine, a purine that modulates dopamine activity. The current study evaluates the effects of a long-term (5-month) ketogenic diet on behavioral, neurochemical, and neuroanatomical measures in PINK1-KO rats, a new animal model of Parkinson’s disease. Both wild-type and PINK1-KO animals fed a ...
The Effects Of Lipopolysaccharide-Induced Neuroinflammation On Learning And Forgetting In Juvenile Rats, 2016 Seton Hall University
The Effects Of Lipopolysaccharide-Induced Neuroinflammation On Learning And Forgetting In Juvenile Rats, Michele Barry
Seton Hall University Dissertations and Theses (ETDs)
The inability to remember events experienced very early in life is referred to as Infantile Amnesia (IA) and has been observed in both humans and animals. Over the years interest in the phenomenon waned, but has recently increased with the discovery of new neurobiological methods to study brain function (e.g., Callaghan, Li & Richardson, 2014). The neurobiological mechanism behind IA has yet to be determined, but several innovative theories have been developed with these new research methods. The neurogenesis hypothesis theorizes that increased neurogenesis during early development disrupts previously established memories. The hippocampus, an area that mediates both the memory ...
Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, 2016 University of Connecticut - Storrs
Exploring The Effect Of Novel Small Molecules On Oligodendrocyte Precursor Proliferation, Sagune Sakya
University Scholar Projects
Gliomas, a type of brain tumor, can be difficult to treat and have a poor survival rate. One pathway that leads to glioma formation is excessive signaling by platelet derived growth factors (PDGF) through PDGF receptor α (PDGFRα). Through this research, I found that novel compounds that downregulate PDGFRα decrease proliferation of Oli-neu cells, an oligodendrocyte precursor cell model, and identified signaling pathways through which these compounds may exert their effect. Further investigation may identify targets for development of glioma treatments.
Ccnf Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, 2016 Macquarie University
Ccnf Mutations In Amyotrophic Lateral Sclerosis And Frontotemporal Dementia, Kelly L. Williams, Jason Kost, Robert H. Brown Jr., John E. Landers, Ian P. Blair
Open Access Articles
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping, fatal neurodegenerative disorders in which the molecular and pathogenic basis remains poorly understood. Ubiquitinated protein aggregates, of which TDP-43 is a major component, are a characteristic pathological feature of most ALS and FTD patients. Here we use genome-wide linkage analysis in a large ALS/FTD kindred to identify a novel disease locus on chromosome 16p13.3. Whole-exome sequencing identified a CCNF missense mutation at this locus. Interrogation of international cohorts identified additional novel CCNF variants in familial and sporadic ALS and FTD. Enrichment of rare protein-altering CCNF variants was evident ...