Molecular and Cellular Neuroscience Commons^™

Phosphodiesterase Inhibition And Adenosine A2b Receptor Signaling In Mitochondrial Function: Pharmacology And Toxicology Of 3-Isobutyl 1-Methylxanthine (Ibmx) In The 661w Retina-Derived Cell Line, Anthony Presley Leonard

MUSC Theses and Dissertations

3-isobutyl 1-methylxanthine (IBMX) is a commonly used inhibitor of cyclic nucleotide phosphodiesterases (PDE) and G protein coupled adenosine receptors. Administration of IBMX to retina photoreceptor-derived 661w cell line results in decreased mitochondrial respiration followed by cell death, mimicking phenomena observed in inherited retina neurodegeneration in humans and animals and thus suggesting their use as a cell-based model of retina degeneration. In this dissertation, the temporal relationship between pathways altered by IBMX and how these pathways affect mitochondrial physiology are evaluated. These studies utilize a novel high content microscopic method for simultaneously measuring mitochondrial morphology and membrane potential in living cultured …

A Mitochondrial Rnai Screen Defines Cellular Bioenergetic Determinants And Identifies An Adenylate Kinase As A Key Regulator Of Atp Levels, Nathan J. Lanning, Brendan D. Looyenga, Audra L. Kauffman, Natalie M. Niemi

University Faculty Publications and Creative Works

Altered cellular bioenergetics and mitochondrial function are major features of several diseases, including cancer, diabetes, and neurodegenerative disorders. Given this important link to human health, we sought to define proteins within mitochondria that are critical for maintaining homeostatic ATP levels. We screened an RNAi library targeting >1,000 nuclear-encoded genes whose protein products localize to the mitochondria in multiple metabolic conditions in order to examine their effects on cellular ATP levels. We identified a mechanism by which electron transport chain (ETC) perturbation under glycolytic conditions increased ATP production through enhanced glycolytic flux, thereby highlighting the cellular potential for metabolic plasticity. Additionally, …

Dopaminergic And Activity-Dependent Modulation Of Mechanosensory Responses In Drosophila Melanogaster Larvae, Josh S. Titlow

Theses and Dissertations--Biology

A central theme of this dissertation is nervous system plasticity. Activity-dependent plasticity and dopaminergic modulation are two processes by which neural circuits adapt their function to developmental and environmental changes. These processes are involved in basic cognitive functions and can contribute to neurological disorder. An important goal in modern neurobiology is understanding how genotypic variation influences plasticity, and leveraging the quantitative genetics resources in model organisms is a valuable component of this endeavor. To this end I investigated activity-dependent plasticity and dopaminergic modulation in Drosophila melanogaster larvae using neurobiological and genetic approaches.

Larval mechanosensory behavior is described in Chapter 2. …

Inhibition Of Phosphodiesterase10a Attenuates Morphine-Induced Conditioned Place Preference, Ying Mu, Zhaoxiang Ren, Jia Jia, Bo Gao, Longtai Zheng, Eitan Friedman

Publications and Research

Background: Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP).

Results: The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of …

The Molecular Components Of Estrogen Receptor Beta (Erβ) Signaling In Neuronal Sytems, Natasha Mott

Dissertations

With increasing life expectancy, women are now living upwards of 50 years without circulating estrogens, therefore, it is essential to investigate how the brain is changed by estrogen deprivation and also how aging influences these changes. The Women's Health Initiative (WHI) study spurred rigorous debate regarding estrogen therapy for postmenopausal women due to dichotomous effects of estrogens in menopausal and post-menopausal women. Meta-analyses of the WHI study revealed that after circulating estrogens are depleted for many years re-exposure may cause aberrant, negative health effects, indicating that there is an age-related `switch' in estrogen signaling around menopause. These age-related effects of …

Characterization Of The Transporter Protein Sodium-Potassium Adenosine Triphosphatase In The Myelin Membrane, Dara E C Schaefer

Theses and Dissertations (Comprehensive)

Sodium-potassium adenosine triphosphatase (Na⁺/K⁺-ATPase) is an integral membrane protein with known involvement in the maintenance of resting membrane potentials, nutrient uptake, cellular signal transduction, and cell-cell adhesion. The functional enzyme contains a catalytic alpha subunit and a glycosylated beta subunit, of which three isoforms of each are known to exist in the central nervous system (CNS). Altered expression and/or activity of Na⁺/K⁺-ATPase subunit isoforms has been previously implicated in the pathophysiology of several neurological disorders. This study characterized Na⁺/K⁺-ATPase expression and distribution in the myelin membrane, identified its …

Repeated Asenapine Treatment Produces A Sensitization Effect In Two Preclinical Tests Of Antipsychotic Activity, Rongyin Qin, Yingzhu Chen, Ming Li

Department of Psychology: Faculty Publications

Among several commonly used atypical antipsychotic drugs, olanzapine and risperidone cause a sensitization effect in the conditioned avoidance response (CAR) and phencyclidine (PCP)- induced hyperlocomotion paradigms – two well established animal tests of antipsychotic drugs, whereas clozapine causes a tolerance effect. Asenapine is a novel antipsychotic drug recently approved for the treatment of schizophrenia and manic disorders. It shares several receptor binding sites and behavioral features with other atypical antipsychotic drugs. However, it is not clear what type of repeated effect (sensitization or tolerance) asenapine would induce, and whether such an effect is transferrable to other atypicals. In this study, …

Iptakalim Attenuates Self-Administration And Acquired Goal-Tracking Behavior Controlled By Nicotine, S. Charntikov, N. Swalve, Steven T. Pittenger, K. Fink, S. Schepers, G. C. Hadlock, A. E. Fleckenstein, G. Hu, Ming Li, Rick A. Bevins

Department of Psychology: Faculty Publications

Iptakalim is an ATP-sensitive potassium channel opener, as well as an a4b2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a responseindependent manner only on nicotine sessions. …

Analysis Of Neuronal And Microglial Responses To Implanted Silicon Devices Through Immunohistochemistry And Clarity, Michael A. Leathers, Kevin J. Otto

The Summer Undergraduate Research Fellowship (SURF) Symposium

Brain computer interfaces (BCI’s) and implantable cortical devices have recently emerged in research as promising treatment methods for a variety of neurological problems such as motor dysfunction, memory loss, and sudden onset seizures. The number of people currently suffering from a loss of nervous system function as a result of neurodegenerative diseases or injury creates a need for reliable neural prostheses. The autoimmune response of the Central Nervous System (CNS) when introduced with a foreign object such as an electrode shank quickly impedes signal strength and degrades the functional life of the device. Two different experimental methods were used to …

The Flexible Fairness: Equality, Earned Entitlement, And Self-Interest, Chunliang Feng, Yi Luo, Ruolei Gu, Lucas S. Broster, Xueyi Shen, Tengxiang Tian, Yue-Jia Luo, Frank Krueger

Behavioral Science Faculty Publications

The current study explored whether earned entitlement modulated the perception of fairness in three experiments. A preliminary resource earning task was added before players decided how to allocate the resource they jointly earned. Participants' decision in allocation, their responses to equal or unequal offers, whether advantageous or disadvantageous, and subjective ratings of fairness were all assessed in the current study. Behavioral results revealed that participants proposed more generous offers and showed enhanced tolerance to disadvantageous unequal offers from others when they performed worse than their presumed "partners," while the reverse was true in the better-performance condition. The subjective ratings also …

Enhanced Nicotine Self-Administration And Suppressed Dopaminergic Systems In A Rat Model Of Diabetes, Laura O'Dell

Selected Works Temporary Series

Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared …

Enhanced Nicotine Self-Administration And Suppressed Dopaminergic Systems In A Rat Model Of Diabetes, Laura O'Dell

Departmental Papers (Psych)

Patients with diabetes display a heightened propensity to use tobacco; however, it is unclear whether they experience enhanced rewarding effects of nicotine. Thus, this study examined the reinforcing effects of nicotine in a rodent model of diabetes involving administration of streptozotocin (STZ), a drug that is toxic to pancreatic insulin-producing cells. The first study compared STZ- and vehicle-treated rats that had 23-hour access to intravenous self-administration (IVSA) of nicotine or saline and concomitant access to food and water. In order to examine the contribution of dopamine to our behavioral effects, dopamine transporter (DAT), D1 and D2 receptor levels were compared …

Investigating Potential Target Genes Of The Rfx Transcription Factor Daf-19 In Caenorhabditis Elegans, He Zhang

Lawrence University Honors Projects

Neurodegenerative diseases, such as Alzheimer’s disease, are characterized by an age-related decrease in the synaptic activity of the patient’s brain. Previous research suggested that a RFX transcription factor DAF-19 in the nematode Caenorhabditis elegans (C. elegans) may be involved in the maintenance of synaptic protein levels. Particularly, worms that were DAF-19A/B defective showed reduced synaptic activities when compared to their age-matched controls.

This study investigated the role of DAF-19A/B isoforms in the C. elegans nervous system. Three genes, F46G11.3, F57B10.9, and F58E2.3 were selected as potential downstream targets of DAF-19A/B based on their potential neuronal expression. …

Trpv1 Channels Contribute To Behavioral Hypersensitivity And Spontaneous Activity In Nociceptors After Spinal Cord Injury, Zizhen Wu

Dissertations and Theses (Open Access)

A majority of persons who have sustained spinal cord injury (SCI) develop chronic pain. While most investigators have assumed that the critical mechanisms underlying neuropathic pain after SCI are restricted to the central nervous system (CNS), recent studies showed that contusive SCI results in a large increase in spontaneous activity in primary nociceptors, which is correlated significantly with mechanical allodynia and thermal hyperalgesia. Upregulation of ion channel transient receptor vanilloid 1 (TRPV1) has been observed in the dorsal horn of the spinal cord after SCI, and reduction of SCI-induced hyperalgesia by a TRPV1 antagonist has been claimed. However, the possibility …

Role Of Neurogranin In The Regulation Of Calcium Binding To Calmodulin, Anuja Chandrasekar

Dissertations and Theses (Open Access)

Role of Neurogranin in the regulation of calcium binding to Calmodulin

Anuja Chandrasekar, B.S

Advisor: M. Neal Waxham, Ph.D

The overall goal of my project was to gain a quantitative understanding of how the interaction between two proteins neurogranin (RC3) and calmodulin (CaM) alters a fundamental property of CaM. CaM, has been extensively studied for more than four decades due to its seminal role in almost all biological functions as a calcium signal transducer. Calcium signals in cardiac and neuronal cells are exquisitely precise and enable activation of some processes while down-regulating others. CaM, with its four calcium binding sites, …

Effects Of Beta Amyloid On The Dna Methylation Status Of An In Vitro Model Of Alzheimer’S Disease, Noor Taher

Senior Honors Theses

Available evidence points toward an epigenetic process in Alzheimer’s disease. This thesis describes the research that was done to investigate changes in DNA methylation using an in vitro model of the disease. Although the results indicated no global changes in methylation levels after treating differentiated IMR-32 cells with beta amyloid, there were several regions of the genome that changed their methylation status. Gene ontology studies revealed that these regions are associated with neuronal differentiation and cell fate genes, thus providing a possible model for the contribution of beta amyloid to the development of Alzheimer’s disease. This study provides incentive to …

Cellular Life Beyond An Individual’S Death, Emily Schmitt

CAHSS Intellectual Conversations

One of the most famous examples of cell lines surviving long after a person has died comes from a tumor found in the body of Henrietta Lacks, who died of cervical cancer in 1950. The study of approximately 50 million tons of her cells, which would conservatively equal the amount of cells in one billion people, has resulted in nearly 11,000 patents, including the polio vaccine. These cells have become a focus of public attention since Rebecca Skloot’s 2010 book, The Immortal Life of Henrietta Lacks. This talk will discuss what happens to cells once they leave our bodies, …

Modulation Of Synaptic Transmission By Adenosine In Layer 2/3 Of The Rat Visual Cortex In Vitro, Nicholas M. Bannon

Master's Theses

No abstract provided.

Exercise Alters Glial Cell Line-Derived Neurotrophic Factor (Gdnf) Protein Content In The Spinal Cord, Monica Janine Mccullough

Dissertations

Neurotrophic factors may play a role in exercise-induced neuroprotective effects; however, it is not known if exercise mediates changes in glial cell line-derived neurotrophic factor (GDNF) protein levels in the spinal cord. The aim of the studies described herein was to determine if exercise alters GDNF protein expression in the lumbar spinal cord of healthy and diseased animals. The lumbar spinal cord was analyzed from adult rats aged 6-, 12-, 18- and 24-months, and from transgenic amyotrophic lateral sclerosis (ALS) mice and wild-type mice aged 3 months. Animals had undergone either forced wheel running, voluntary wheel running or swimming for …

Locus Coeruleus And Hippocampal Tyrosine Hydroxylase Levels In A Pressure-Overload Model Of Heart Disease, Luke A. Johnson

Undergraduate Honors Theses

Studies have indicated that approximately 30% of people with heart disease experience major depressive disorder (MDD). Despite strong clinical evidence of a link between the two diseases, the neurobiological processes involved in the relationship are poorly understood. A growing number of studies are revealing similar neuroanatomical and neurochemical abnormalities resulting from both depression and heart disease. The locus coeruleus (LC) is a group of neurons in the pons that synthesize and release norepinephrine, and that is known to play a significant role in depression pathobiology. For example, there is evidence that tyrosine hydroxylase (TH) is elevated in the LC in …