The Effects Of A Ketone Body On Synaptic Transmission,
2019
University of Kentucky
The Effects Of A Ketone Body On Synaptic Transmission, Alexandra Elizabeth Stanback
Theses and Dissertations--Biology
The ketogenic diet is commonly used to control epilepsy, especially in cases when medications cannot. The diet typically consists of high fat, low carb, and adequate protein and produces a metabolite called acetoacetate. Seizure activity is characterized by glutamate excitotoxicity and therefore glutamate regulation is a point of research for control of these disorders. Acetoacetate is heavily implicated as the primary molecule responsible for decreasing glutamate in the synapse; it is believed that acetoacetate interferes with the transport of glutamate into the synaptic vesicles. The effects on synaptic transmission at glutamatergic synapses was studied in relation to the ketogenic diet …
Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity,
2019
CUNY City College
Mechanisms Of Microglia Mediated Apolipoprotien E Neurotoxicity, Pardeep Singh
Dissertations and Theses
No abstract provided.
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 …
Behavioral And Molecular Analysis Of Memory In The Dwarf Cuttlefish,
2019
Georgia Southern University
Behavioral And Molecular Analysis Of Memory In The Dwarf Cuttlefish, Jessica M. Bowers
College of Graduate Studies: Theses & Dissertations
Complex memory has evolved because it benefits animals in all areas of life, such as remembering the location of food or conspecifics, and learning to avoid dangerous stimuli. Advances made by studying relatively simple nervous systems, such as those in gastropod mollusks, can now be used to study mechanisms of memory in more complex systems. Cephalopods offer a unique opportunity to study the mechanisms of memory in a complex invertebrates. The dwarf cuttlefish, Sepia bandensis, is a useful memory model because its fast development and small size allows it to be reared and tested in large numbers. However, primary literature …
Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder,
2019
Scripps College
Evidence-Based Probiotic Intervention For Behavioral And Social Deficits In Autism Spectrum Disorder, Allisen To
Scripps Senior Theses
Autism Spectrum Disorder (ASD) refers to a heterogeneous neurological condition characterized by repetitive and restrictive behaviors and social communication deficits. ASD diagnoses are at a record high, at approximately 1 in 59 children according to the US Center for Disease Control. Currently, there are no available interventions that effectively treat the core symptoms of ASD. All pharmaceutical options address comorbid side effects of ASD but not core deficits and are particularly associated with negative side effects. Additionally, there are economic and geographic barriers that can prevent families of individuals with ASD from seeking or receiving effective interventions. Many of the …
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. …
Induction Of Cerebral Hyperexcitability By Peripheral Viral Challenge: Role Of Cxcl10 Chemokine,
2019
West Virginia University
Induction Of Cerebral Hyperexcitability By Peripheral Viral Challenge: Role Of Cxcl10 Chemokine, Tiffany J. Petrisko
Graduate Theses, Dissertations, and Problem Reports (ETD)
Peripheral viral infections are potent comorbid factors that exacerbate neurodegeneration. Although the underlying mechanisms have not been defined, neuronal hyperexcitability has been established as an underlying feature. Our lab has developed a preclinical model in which a viral mimetic, polyinosinic-polycytidylic acid (PIC) is injected intraperitoneally to induce an anti-viral acute phase response (APR). APR in turn elicits robust neuronal hyperexcitability. The present study was undertaken to characterize molecular mechanisms that mediate the development of hyperexcitability in response to PIC challenge. The analysis of brain tissue after PIC challenge revealed a robust elevation of CXCL10 chemokine, indicating its putative role in …
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 …
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 …
Sonic Hedgehog Is Expressed By Hilar Mossy Cells And Regulates Cellular Survival And Neurogenesis In The Adult Hippocampus,
2019
Case Western Reserve University
Sonic Hedgehog Is Expressed By Hilar Mossy Cells And Regulates Cellular Survival And Neurogenesis In The Adult Hippocampus, Luis E. Gonzalez-Reyes, Chia-Chu Chiang, Mingming Zhang, Joshua Johnson, Manuel Arrillaga-Tamez, Nicholas H. Couturier, Neha Reddy, Lev Starikov, Jeffrey R. Capadona, Andreas H. Kottmann, Dominique M. Durand
Publications and Research
Sonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration …
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 …
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 …
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 …
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 …
