Neuroscience and Neurobiology Commons^™

N-Alkyl 4-Methylamphetamine Enantiomers And The Implication For Potential Modulation Of Abuse Liability And Enhancement Of Psychoactive Drug Targeting., Ramsey Sitta

Theses and Dissertations

Drugs of abuse have a long history in humanity. Currently however, a subject of great interest is the phenylalkylamine family of drugs. Not only is the abuse liability of interest but also the potential therapeutic expansion of the capabilities of this family of drugs by utilizing the unique stereospecific effects of the newly discovered hybrid compounds. Based upon prior data of N-Alkyl 4-MA the enantiomers of N-Methyl, N-Ethyl, and N-Propyl were analyzed in hDAT, hNET, and hSERT. It was found that there was a negative correlation between chain length and potency and dopaminergic component. In agreement with the currently established …

Metabolic And Morphologic Shifts In Neuro2a Cells Cultured In Galactose Medium, Leah Welker

Masters Theses

It has been observed that highly-proliferating cells, such as cancer cells, rely mainly on glycolysis for ATP production, regardless of presence of oxygen. This effect, however, can be reversed by changing the main energy substrate in the medium from glucose to galactose. The oxidation of galactose in glycolysis yields less net ATP, presumably forcing the cell into OXPHOS. This has been established in many cell lines, including HeLA, HepG2, and skeletal muscle cells. As of yet, this has not been reproduced in neuronal cells. Using Neuro2a, a murine neuroblastoma cell line, this study exposes neuronal cells to galactose medium, and …

Quantification Of Brain-Region Specific Alterations In Insulin-Like Growth Factor-1 Expression During Developmental Hypothyroidism, Cari Lee Graber-Feesl

All Graduate Theses, Dissertations, and Other Capstone Projects

Insufficient thyroid hormone (TH) during development results in permanent neurological deficits. These deficits are the result of perturbed TH-mediated brain development. Interestingly, insufficient insulin-like growth factor 1 (Igf-1) during development results in neurological deficits that are similar to those reported for developmental hypothyroidism. This observation suggests that deficits associated with low TH during development may be the result of altered Igf-1 expression in the developing brain. To test this, timed-pregnant mice were treated with thyroid gland inhibitors from gestational day 16 (GD16) until postnatal day 21 (P21) to induce a hypothyroid state. A parallel set of untreated timed-pregnant mice were …

Cx43 Expression Increases In Response To Increased Temperature Incubation In The Developing Chicken Embryonic Brain, Erick A. Barrios

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We used the chicken embryo model to examine whether altered incubation temperature during chicken embryo development would alter the protein expression of heat shock protein 70 (hsp70), hsp90, and connexin 43 (cx43) in the brain. We incubated eggs in either optimal (37.6°C, Con), increased (39.6°C, +2), or decreased (35.6°C, -2) temperature conditions until they reached embryonic day 16 (E16). The -2 condition significantly increased incidence of embryonic mortality. As shown in the literature, the development of the eggs was accelerated or decelerated due to increased or decreased temperature respectively. To control for this, we incubated eggs at optimal temperature (37.6°C) …

Upstream Regulators Of Vrac Activation In Human 1321n1 Astrocytoma Cells, Courtney Elyse Moore

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Cells rely on a constant volume not only for structural stability but also for normal homeostatic processes to occur. In the brain and CNS, cells can regain their normal volume through a process termed regulatory volume decrease (RVD). A key component of a cells' response to cell swelling is the activation of channel(s) responsible for the efflux of chloride current, ICl,swell. Volume regulated anion channels (VRAC) which mediate ICl,swell have been implicated in controlling cell volume during RVD, but the mechanisms which activate this channel are not completely understood. In this study, I examined the role of G protein-coupled signaling …

Hydrogen Sulfide Regulation Of Kir Channels, Junghoon Ha

Theses and Dissertations

Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol- 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. Gasotransmitters, such as carbon monoxide (CO), have been reported to regulate the activity of Kir channels by altering channel-PIP2 interactions. We tested, in a model system, the effects and mechanism of action of another important gasotransmitter, hydrogen sulfide (H2S) thought to play a key role in cellular responses under ischemic conditions. Direct administration of sodium hydrogen sulfide (NaHS), as an exogenous H2S source, …

The Hypercapnic Ventilatory Response And Behavior In Ca2+-Activated K+ (Bk) Channel Knock Out Mice And T-Cell Death-Associated Gene 8 (Tdag8) Receptor Knock Out Mice, Christine Annette Ratliff-Rang

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Some acid sensing areas in the brain control the expression of breathing and anxiety/fear including the locus coeruleus (LC) (Redmond & Huang, 1979) and the nucleus tractus solitarius (NTS). It has been found that knocking out T-cell death-associated gene 8 (TDAG8), a chemosensor, attenuates CO2 induced fear phenotypes in mice. However their hypercapnic ventilatory response (HCVR) has not yet been looked at. Also, BK channels are large-conductance, calcium-activated potassium channels that are activated by increases in concentration of intracellular calcium ions. It has been found that BK KO rats have an increase in their HCVR (Patrone et al., 2014) however …

Is Mitochondrial Development Impaired In Hyperoxic Rats And Does This Underpin The Blunting Of The Acute Hypoxic Ventilatory Response?, Tariq Hasan Fayyad

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Carotid body (CB) responses to hypoxia are low at birth and increase over time to mature responses. Using an in vitro rat CB-carotid sinus nerve (CSN) preparation, Kholwadwala and Donnelly (1992) demonstrated that the CSN activity in response to hypoxia increased from low levels to robust adult responses after two weeks. This time course of maturation was paralleled by an increase in TASK channel sensitivity to hypoxia in the O2-sensing Type I cells (Kim et al, 2011). Previous studies have indicated that a fall in Type I cell mitochondrial volume and an increase in the rate of oxidative phosphorylation may …

Measuring The Effects Of High-Fat Diet On Breathing And Oxygen-Sensitivity Of The Carotid Body Type I Cell, Ryan J. Rakoczy

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The carotid bodies (CB), the primary peripheral chemoreceptors, respond to changes in blood gases with neurotransmitter release, thereby increasing carotid sinus nerve firing frequency and ultimately correcting the pattern of breathing. It has previously been demonstrated that acute application of the adipokine leptin caused perturbations of intracellular calcium and membrane ion movement in isolated CB Type I cells (Pye et al, 2015) and augmented the response of the intact CB to hypoxia (Pye et al, 2016). This study's aim was to examine, in-vivo, if elevated leptin modulated CB function and breathing. Rats were fed high-fat chow or control chow for …

Investigating The Role Of An Sk Channel Activator On Survival And Motor Function In The Sod1-G93a, Als Mouse Model, Matthew Thomas Dancy

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Amyotrophic Lateral Sclerosis (ALS) is a fatal, adult-onset progressive degenerative motor neuron disease that is characterized by muscle atrophy and weakness due to the loss of upper and lower motor neurons. Average survival time for individuals diagnosed with the disease is three to five years; currently there is no cure and only one drug approved by the Food and Administration (FDA). Scientists have proposed various theories in order to solve the mystery which surrounds ALS. One of these theories hypothesizes how hyperexcitability and excitotoxicity leads to the death of motor neurons. In this study, we will address ways of combatting …

The Effect Of Cold On The Physiology Of Drosophila Larva Heart And On Synaptic Transmission At Crayfish Neuromuscular Junctions, Yuechen Zhu

Theses and Dissertations--Biology

Ectothermic animals are susceptible to temperature changes such as cold shock with seasons. To survive through a cold shock, ectotherms have developed unique strategies. My interest is focusing on the physiological function of during cold shock and prolonged cold exposure in the fruit fly (Drosophila melanogaster) and crayfish (Procambarus clarkii). I used Drosophila melanogaster as a model system to investigate cardiac function in response to modulators (serotonin, acetylcholine, octopamine, dopamine and a cocktail of modulators) in acute cold shock and chronic cold shock conditions as possible mechanism to regulate heart rate in the cold. To examine if the dampened heart …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Dopamine Effects Of Stimulant And Non-Stimulant Drugs Used In The Treatment Of Attention Deficit Hyperactivity Disorder, Preeti Chalwadi

Theses and Dissertations

Attention deficit hyperactivity disorder (ADHD) is thought to be associated with dysfunction of ascending catecholamine neuronal systems, particularly dopamine (DA) and norepinephrine (NE). Dysfunction of these catecholamine neurons innervating the prefrontal cortex is hypothesized to underlie impaired executive functions. Dysfunction of the DA neurons innervating the striatum is additionally hypothesized to underlie deficits in motivation and reinforcement learning. However, mechanisms of action of therapeutic drugs used for treating ADHD have mainly focused on catecholamines in the prefrontal cortex and have not adequately addressed the role played by DA signaling in the striatum. Stimulants such as Adderall® and Ritalin® are chemically …

Design Of Novel Ion Channel Modulators, Vladimir Yarov-Yarovoy

Science Seminar Series

Function and modulation of neuronal sodium channels are critical for the neuromodulation of electrical excitability and synaptic transmission in neurons - the basis for many aspects of signal transduction, learning, memory and physiological regulation. Mutations in neuronal voltage-gated sodium channel genes are responsible for various human neurological disorders. Furthermore, human neuronal voltage-gated sodium channels are primary targets of therapeutic drugs used as local anesthetics and for treatment of neurological and cardiac disorders. Yarov-Yarovoy's lab is working on rational design of novel therapeutically useful blockers of voltage-gated sodium channels for treatment of pain and epilepsy. Serious, chronic pain affects at least …

Structural Dichotomy Of The Mind; The Role Of Sexual Neuromodulators, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

The mind (mental function) and sexuality represent two distinct environmental functions, but which are supported within the brain by a common (somatic-autonomic) neurobiological substrate. As a consequence, mental function takes on autonomic characteristics from the sexual-autonomic system (like autonomy, duality), while sexual function takes on features from mental functioning (such as lateralization). In this paper we discuss the lateralized action of two classes of sexual neuromodulators: hormones and pheromones. This process of lateralization is assimilated with the structural dichotomy of the mind.

A relatively similar process but related to informational dichotomy of the mind will be presented in a forthcoming …

Exploring The Relationship Between Behaviour And Neurochemistry In The Polyphenic Spider, Anelosimus Studiosus (Araneae: Theridiidae), Jennifer B. Price

Electronic Theses and Dissertations

The importance of social behaviour is evident in human society, but there are both costs and benefits associated with cooperation and sociality throughout the animal kingdom. At what point do the benefits outweigh the costs, and when do selective pressures favour sociality and colonization over solitude and independence? To investigate these questions, we have focused on an anomalous species of spider, Anelosimus studiosus, also known now as the northern social spider. Throughout its broad range, A. studiosus is solitary and aggressive, but recently, colonies of cooperative and social individuals have been observed at northern latitudes. This leads to two …

Diffuse Traumatic Brain Injury Induces Prolonged Immune Sysregulation And Potentiates Hyperalgesia Following A Peripheral Immune Challenge, Rachel K. Rowe, Gavin I. Ellis, Jordan L. Harrison, Adam D. Bachstetter, Gregory F. Corder, Linda J. Van Eldik, Bradley K. Taylor, Francesc Marti, Jonathan Lifshitz

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Background: Nociceptive and neuropathic pain occurs as part of the disease process after traumatic brain injury (TBI) in humans. Central and peripheral inflammation, a major secondary injury process initiated by the traumatic brain injury event, has been implicated in the potentiation of peripheral nociceptive pain. We hypothesized that the inflammatory response to diffuse traumatic brain injury potentiates persistent pain through prolonged immune dysregulation.

Results: To test this, adult, male C57BL/6 mice were subjected to midline fluid percussion brain injury or to sham procedure. One cohort of mice was analyzed for inflammation-related cytokine levels in cortical biopsies and serum along an …

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.

Development Of Vip-Sst Interneuron Associations In Mouse Neocortex And Entorhinal Cortex, Aayushi A. Mehta

Honors Scholar Theses

Cortical networks depend upon inhibition through the neurotransmitter GABA to control and coordinate specific spatiotemporal circuit patterns, underlying the exquisite complexity of neural signaling. Disinhibition, a form of inhibition where inhibitory neurons inhibit other inhibitory cells, further aids in amplifying local neural processing in a selective, organized manner. A subset of GABAergic interneurons, vasoactive intestinal peptide-expressing (VIP) cells, preferentially inhibit somatostatin interneurons, which provide inhibitory input onto pyramidal cells, thus creating an archetypal circuit illustrating disinhibition in the cortex. The aim of this anatomical study was to investigate variations in GABAergic VIP synapses onto somatostatin-expressing inhibitory interneurons in mice at …

The Influence Of Canine Aggression And Behavioral Treatment On Heart Rate Variability, Lydia Craig

Psychology Honors Projects

Dog aggression affects many, with nearly 5 million dog bites reported yearly in the United States alone. With the physical, emotional, and monetary costs of bites, it is of considerable interest to identify dogs that are likely to bite. One physiological measure that might serve as an index of aggression is heart rate variability (HRV), which refers to vagally mediated beat-to-beat change in heart rate. Low HRV has been associated with impaired emotional and behavioral regulation and stress in both humans and animals. To assess whether this measure corresponds with aggression in dogs, resting HRV was measured for dogs with …

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

Effect Of Prior Trauma Exposure On Alpha Amplitude, Heart Rate, And Self-Reported Negative Affect, Gina L. Denoble

All Master's Theses

This study was conducted to investigate whether the number of traumatic events an individual has previously experienced influences that individual’s physiological and psychological reactions when exposed to a negative affective stimulus followed by a mindfulness-based stress reduction (MBSR) intervention. Twenty-eight participants were placed into intact quasi-experimental groups based on their scores on the Traumatic Life Events Questionnaire (TLEQ). The negative affective stimulus consisted of a series of photos bearing negative affective valence. The photos were selected from the International Affective Picture System (IAPS), and paralleled the areas of trauma exposure evaluated by the TLEQ. All participants were exposed to the …

Cross Sensitization Of Depressive-Like Behavior Through Two Depression Related Paradigms: Maternal Separation And Its Effect On The Forced Swim Test In The Guinea Pig, Amanda Danielle Schreibeis

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Separation and Its Effect on the Forced Swim Test In the Guinea Pig Early-life stress such as parental neglect, absence, or abandonment, has been hypothesized to increase the susceptibility for developing depression later in life via sensitization of stress-responsive physiological systems (e.g., pro-inflammatory cytokines, hypothalamic-pituitary-adrenal axis). Guinea pigs offer a potential model, but study has been limited to behavioral observations obtained during maternal separation tests. This thesis examined the generalization of this response by asking whether it would cross-sensitize to behavior in another depressive-related paradigm, the forced swim test. In three experiments, pups underwent three forced swim trials, in shallower …

Sk Channel Clustering In Sod1-G93a Motoneurons, Saihari Shekar Dukkipati

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Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease that currently has no cure and extremely limited treatment options. The specific mechanisms that underlie motoneuron degeneration and death, which are classical features of this disease, are mostly unknown. This thesis tests the hypothesis that small-conductance calcium-activated potassium channels (SK) may be downregulated in ALS motoneurons, as suggested by computational modelling. SK channel expression was measured in spinal alpha-motoneuron cell bodies or somata of wildtype (WT) and mutant (mt) SOD1-G93A mice, a transgenic animal model of ALS. Quantitative immunohistochemical analysis of the developmental expression of SK channel isoforms SK2 and SK3 …

Social Buffering By Unfamiliar Adult Males In Preweaning Guinea Pigs (Cavia Pocellus): The Effects On Hpa Activity And Fos Induction In The Medial Prefrontal Cortex, Withayapon Watanasriyakul

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Social buffering, a phenomenon in which the presence of a social partner can reduce stress responses, is often most effective between strongly attached partners. Our laboratory previously found a surprising buffering effect of the hypothalamic-pituitary-adrenal (HPA) response in preweaning guinea pigs by unfamiliar adult males. It was hypothesized that this HPA-buffering effect was driven by social interactions between the two partners and may involve an activation of the prelimbic cortex. Therefore, the current study examined these potential associations. To limit social interactions, the adult male was anesthetized in one condition compared to another condition where the adult male remained conscious. …

The Use Of Doublecortin To Quantify The Effects Of Pharmacological Treatment On Neurogenesis And Functional Recovery After Stroke, Amber Lee Hensley

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Ischemic strokes account for 87% of all strokes and can have debilitating effects on language, sensory, and motor skills. Currently, tPA is the only medication approved by the FDA for the treatment of ischemic stroke, but the window of time to administer the drug is very small. In this thesis, we investigate the use of a simvastatin and fluoxetine drug combination (FS) as a possible treatment for ischemic stroke victims. To analyze the effects of FS on neurogenesis and functional recovery, we utilize the Montoya Staircase and quantify the amount of neurogenesis using doublecortin. Although the results of this study …

Examination Of A Post-Stroke Drug Treatment For Its Effect On Blood Brain Barrier Permeability, And Gene Expression Changes In The Peri-Infarct Region, Ankita Anil Patel

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In this current study, we have investigated this a combination of fluoxetine, simvastatin and ascorbic acid administered daily beginning at 20-26 hours after stroke induction. We hope to understand therapeutic abilities by studying its effectiveness on the blood brain barrier permeability and gene expression changes of the microglial subtypes involved in neuro-inflammation and neurogenesis factors in the peri-infarct region. Our results indicate that S-enantiomer of fluoxetine may be more beneficial compared to the R-enantiomer. The S-enantiomer was effective in tightening the blood brain barrier in contrast to the R-enantiomer, in which the latter showed a greater Evans Blue dye permeability …

Intrinsic And Extrinsic Regulation Of Pineal Melatonin Rhythms, Ye Li

Theses and Dissertations--Biology

Circadian rhythm is a biological rhythm with period of about 24 hours. Circadian rhythm is universal in phyla from bacteria to mammals and exists in different level from gene expression to behavior. Circadian system consists of three components: 1) a self-sustained oscillator; 2) an input pathway which can alter the phase of the oscillator; and 3) an output such as gene expression, enzyme activity, hormone production, heart rate, body temperature or locomotor activities. The way the oscillator regulates its outputs is complicated, in that on one hand usually the oscillator is not the only factor affecting the outputs, and on …

Anthropomorphic Denial Of Fish Pain, Lynne U. Sneddon, Matthew C. Leach

Animal Sentience

Key (2016) affirms that we do not know how the fish brain processes pain but denies — because fish lack a human-like cortex — that fish can feel pain. He affirms that birds, like fish, have a singly-laminated cortex and that the structure of the bird brain is quite different from that of the human brain, yet he does not deny that birds can feel pain. In this commentary we describe how Key cites studies that substantiate mammalian pain but discounts the same kind of data as evidence of fish pain. We suggest that Key's interpretations are illogical, do not …

High Affinity Block Of Icl,Swell By Thiol-Reactive Small Molecules, Sung H. Park

Theses and Dissertations

Ebselen (Ebs) is considered as a glutathione peroxidase (GPx) mimetic and primarily thought to function by scavenging intracellular reactive oxygen species (ROS). Previous to our work, Deng et al. (2010a) demonstrated complete block of I_Cl,swell with 15 microM Ebs following endothelin-1 (ET-1) induced activation of the current in cardiomyocytes. This block was presumed to take effect mainly via the quenching of ROS. Nonetheless, our work with DI TNC1 astrocytes strongly emphasizes that Ebs might function by an alternative mechanism based on its kinetic profile in blocking I_Cl,swell. Our experiments showed that 45 nM Ebs can fully block …