Sodium Channel Distribution In The Apical Dendrites Of Pyramidal Cells Vary In The Hindbrain Of Apteronotus Leptorhynchus.,
2019
West Virginia University
Sodium Channel Distribution In The Apical Dendrites Of Pyramidal Cells Vary In The Hindbrain Of Apteronotus Leptorhynchus., Sree Indrani Motipally
Graduate Theses, Dissertations, and Problem Reports (ETD)
Apteronotid weakly electric fish heavily rely on their electrosensory system for behaviors like spatial navigation, communication and prey capture. Since the behaviorally important information about their environment is contained in the spatial and temporal modulations of the electrosensory signal, efficient mechanisms to process this information with great fidelity are of the utmost importance. Efficient sensory processing often involves having multiple parallel processing streams so that each stream can specialize to treat signals with different properties. This strategy requires the response properties and neural dynamic to be adjusted in each pathway to implement different neural coding strategies. One of the neural …
Role Of Extracellular Vesicles In Neuroinflammatory Progression And Mitochondrial Functional Alterations,
2019
West Virginia University
Role Of Extracellular Vesicles In Neuroinflammatory Progression And Mitochondrial Functional Alterations, Ashley E. Russell
Graduate Theses, Dissertations, and Problem Reports (ETD)
Inflammation within the central nervous system (CNS), termed neuroinflammation, is a defining characteristic of many neuropathological conditions, including Alzheimer’s disease (AD) and stroke. Certain inflammatory mediators activate the transcription factor NF-κB, which induces transcription of many pro-inflammatory genes, including miR-34a and miR-146a. Several target candidate genes of these miRNAs encode for proteins of the mitochondrial electron transport chain. In our studies, we demonstrate that in response to inflammatory stimuli, such as TNF-α, the expression of miR-34a and -146a is significantly increased in several CNS cell types, and in their secreted extracellular vesicles (EVs). Exposure to TNF-α-derived EVs significantly increases cellular …
Regulator Of G Protein Signaling-12 (Rgs12) In Dopaminergic And Kappa Opioid Receptor-Dependent Signaling And Behavior,
2019
West Virginia University
Regulator Of G Protein Signaling-12 (Rgs12) In Dopaminergic And Kappa Opioid Receptor-Dependent Signaling And Behavior, Joshua David Gross
Graduate Theses, Dissertations, and Problem Reports (ETD)
Dopaminergic neurotransmission is critically involved in the etiology and treatment of many psychiatric and neurological disorders. One modulator of dopaminergic neurotransmission is the kappa opioid receptor (KOR) -- a G protein-coupled receptor (GPCR) that is densely expressed within dopaminergic neurons and circuits. GPCRs are tightly regulated by a variety of intracellular signaling molecules, including Regulator of G Protein Signaling (RGS) proteins. Canonically, RGS proteins act as GTPase accelerating proteins (GAPs) on GTP-bound Ga subunits following GPCR activation, thereby hastening the rate at which GPCR-mediated G protein signaling is terminated. However, some RGS proteins exhibit more complex mechanisms of action on …
Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain,
2019
Virginia Commonwealth University
Spag17 Deficiency Impairs Neuronal Cell Differentiation In Developing Brain, Olivia J. Choi
Theses and Dissertations
The development of the nervous system is a multi-level, time-sensitive process that relies heavily on cell differentiation. However, the molecular mechanisms that control brain development remain poorly understood. We generated a knockout (KO) mouse for the cilia associated gene Spag17. These animals develop hydrocephalus and enlarged ventricles consistent with the role of Spag17 in the motility of ependymal cilia. However, other phenotypes that cannot be explained by this role were also present. Recently, a mutation in Spag17 has been associated with brain malformations and severe intellectual disability in humans. Therefore, we hypothesized that Spag17 plays a crucial role in …
Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents,
2019
Virginia Commonwealth University
Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies
Theses and Dissertations
Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …
Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action,
2019
Virginia Commonwealth University
Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra
Theses and Dissertations
Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …
An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum,
2019
Virginia Commonwealth University
An Investigation On The Role Of Β-Arrestin 2, Protein Kinase C And Sex On The Mechanism Of Morphine Tolerance In The Mouse Ileum, Karan Hitesh Muchhala
Theses and Dissertations
Opioids such as morphine are frequently used in the clinic to treat pain. However, the perennial bane of chronic opioid use is the rapid development of tolerance to the analgesic effects but delayed development of tolerance to the respiratory depressant and constipating effects. As constipation is one of the most common opioid-related adverse effects in humans, it is important to delineate mechanisms that drive opioid tolerance in the ileum and lack of it in the colon. The overarching goal of this thesis was to investigate mechanisms of morphine tolerance in the ileum by comparing the mechanism of morphine tolerance in …
Improving Dopamine Monitoring With Ncam And The Effects Of Intranasal Oxytocin On Dopamine Signaling In The Rat Brain,
2019
Eastern Washington University
Improving Dopamine Monitoring With Ncam And The Effects Of Intranasal Oxytocin On Dopamine Signaling In The Rat Brain, Darren Earl Ginder
EWU Masters Thesis Collection
Dopamine (DA) is a neurohormone highly involved in learning and memory. Oxytocin (OXT), another neurohormone, has also been implicated in learning and memory. Fast-scan cyclic voltammetry (FSCV) is a method used for the real-time examination of DA neurotransmission in the brain. Implanting FSCV electrodes is an invasive technique that likely results in an inflammatory response (i.e. gliosis) that can restrict FSCV recording of DA signals. Neural cell adhesion molecule (NCAM) may reduce gliosis and potentially improve the ability of FSCV electrodes to monitor DA signaling. Chapter 1 Methods: FSCV electrodes were coated with NCAM and implanted in the rat brain. …
The Progression Of Aβ Proteins In The Retrosplenial Cortex Using An App/Ps1 Alzheimer’S Disease Transgenic Rodent Model,
2019
The College of Wooster
The Progression Of Aβ Proteins In The Retrosplenial Cortex Using An App/Ps1 Alzheimer’S Disease Transgenic Rodent Model, Maha H. Rashid
Senior Independent Study Theses
Alzheimer’s disease is the most common form of dementia in the world with a new case of dementia diagnosed every 3.2 seconds. For over 25 years the amyloid cascade hypothesis has existed as a mechanism of understanding and diagnosing Alzheimer’s Disease. The amyloid cascade hypothesis suggests that Alzheimer’s Disease is sequential in protein progression and proliferative from the medial temporal lobe to the rest of the brain. Hypometabolism of brain regions has also been correlated to plaque deposition and hypometabolism is observed in brain regions that make up the default mode network, specifically the retrosplenial cortex, which is not accounted …
Differential Expression Of Genes Related To Innate Immune Responses In Ex Vivo Spinal Cord And Cerebellar Slice Cultures Infected With West Nile Virus,
2018
University of Southern Mississippi
Differential Expression Of Genes Related To Innate Immune Responses In Ex Vivo Spinal Cord And Cerebellar Slice Cultures Infected With West Nile Virus, Amber M. Paul, Parminder J.S. Vig, Deyin Lu, Ram Kuwar, Maria Lopez, Dobrivoje S. Stokic, A. Arturo Leis, Michael R. Garrett, Fengwei Bai
Publications
West Nile virus (WNV) infection results in a spectrum of neurological symptoms, ranging from a benign fever to severe WNV neuroinvasive disease with high mortality. Many who recover from WNV neuroinvasive infection present with long-term deficits, including weakness, fatigue, and cognitive problems. While neurons are a main target of WNV, other cell types, especially astrocytes, play an important role in promoting WNV-mediated central nervous system (CNS) damage. Conversely, it has been shown that cultured primary astrocytes secrete high levels of interferons (IFNs) immediately after WNV exposure to protect neighboring astrocytes, as well as neurons. However, how intrinsic responses to WNV …
Polyglutamine Repeat Proteins Disrupt Actin Structure In Drosophila Photoreceptors.,
2018
University of San Diego
Polyglutamine Repeat Proteins Disrupt Actin Structure In Drosophila Photoreceptors., Annie Vu, Tyler Humphries, Sean Vogel, Adam Haberman
Biology: Faculty Scholarship
Expansions of polygutamine-encoding stretches in several genes cause neurodegenerative disorders including Huntington's Disease and Spinocerebellar Ataxia type 3. Expression of the human disease alleles in Drosophila melanogaster neurons recapitulates cellular features of these disorders, and has therefore been used to model the cell biology of these diseases. Here, we show that polyglutamine disease alleles expressed in Drosophila photoreceptors disrupt actin structure at rhabdomeres, as other groups have shown they do in Drosophila and mammalian dendrites. We show this actin regulatory pathway works through the small G protein Rac and the actin nucleating protein Form3. We also find that Form3 has …
Investigating Autophagy Dysfunction Induced By A Parkinson's Disease-Causing Mutation In Vps35,
2018
Boise State University
Investigating Autophagy Dysfunction Induced By A Parkinson's Disease-Causing Mutation In Vps35, Abir Ashfakur Rahman
Boise State University Theses and Dissertations
Parkinson’s Disease (PD) is an idiopathic disorder with no known cure. With number of cases steadily rising around the world, it is imperative to turn to the underlying cellular and molecular mechanisms of the disease manifestation and neurodegeneration to craft novel modes of therapy. VPS35 is one of the few genes that have identified and definitively linked to familial PD. The particular mutation that has been associated is known to cause dysfunction of a key cellular process known as autophagy. This process is primarily responsible for clearance of unwanted, damaged or misfolded proteins, among other things. Our study reveals an …
Hypothalamic Circuits In The Control Of Feeding And Emotional Behaviors,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Hypothalamic Circuits In The Control Of Feeding And Emotional Behaviors, Leandra Mangieri
Dissertations and Theses (Open Access)
Feeding results from the integration of both nutritional and affective states, and is guided by complex neural circuitry in the brain. The hypothalamus is a critical center controlling feeding and motivated behaviors. We found that targeted photostimulation of projections from the lateral hypothalamus (LH) to the paraventricular hypothalamus (PVH) in mice elicited voracious feeding and repetitive self-grooming behavior. GABA neurotransmission in the LH->PVH circuit mediated the evoked feeding behavior, and elicited behavioral approach, whereas glutamate release promoted repetitive self-grooming, which was stress-related in nature. Optogenetic inhibition of LHGABA ->PVH circuit reduced feeding after fasting, whereas photostimulation abruptly …
Cell Specific Control Of The Pallidostriatal Pathway,
2018
Illinois Mathematics and Science Academy
Cell Specific Control Of The Pallidostriatal Pathway, Shubha Verma '19
Student Publications & Research
Parkinson’s Disease is a neurodegenerative disorder of the basal ganglia. The main cause for Parkinson’s Disease is the depletion of dopamine, a neurotransmitter. The basal ganglia contains four major nuclei: the substantia nigra, the subthalamic nucleus, the external globus pallidus, and the striatum. These nuclei communicate with each other by the use of neurons.
Heat Shock Protein 40 And Immune Function In Altered Gravity,
2018
NASA Ames Research Center, Universities Space Rsearch Association
Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya
Publications
In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …
Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity,
2018
Universities Space Research Association
Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya
Publications
In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …
Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1I249/M280 Variant,
2018
University of Texas at San Antonio
Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1I249/M280 Variant, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Richard M. Ransohoff, Astrid E. Cardona
Peer Reviewed Articles
Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …
Hyperphosphorylation Of Tau Associates With Changes In Its Function Beyond Microtubule Stability,
2018
CUNY College of Staten Island
Hyperphosphorylation Of Tau Associates With Changes In Its Function Beyond Microtubule Stability, Alejandra D. Alonso, Leah S. Cohen, Christopher Corbo, Viktoriya Morozova, Abdeslem Elldrissi, Greg R. Phillips, Frida E. Kleiman
Publications and Research
Tau is a neuronal microtubule associated protein whose main biological functions are to promote microtubule self-assembly by tubulin and to stabilize those already formed. Tau also plays an important role as an axonal microtubule protein. Tau is an amazing protein that plays a key role in cognitive processes, however, deposits of abnormal forms of tau are associated with several neurodegenerative diseases, including Alzheimer disease (AD), the most prevalent, and Chronic Traumatic Encephalopathy (CTE) and Traumatic Brain Injury (TBI), the most recently associated to abnormal tau. Tau post-translational modifications (PTMs) are responsible for its gain of toxic function. Alonso et al. …
Tributyltin Inhibits Neural Induction Of Human Induced Pluripotent Stem Cells,
2018
National Institute of Health Sciences
Tributyltin Inhibits Neural Induction Of Human Induced Pluripotent Stem Cells, Shigeru Yamada, Yusuke Kubo, Daiju Yamazaki, Yuko Sekino, Yoko Nomura, Sachiko Yoshida, Yusunari Kanda
Publications and Research
Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the …
The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis,
2018
Rowan University
The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert
Graduate School of Biomedical Sciences Theses and Dissertations
Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …
