Molecular and Cellular Neuroscience Commons^™

C. Elegans Avoids Toxin-Producing Streptomyces Using A Seven Transmembrane Domain Chemosensory Receptor, Alan Tran, Angelina Tang, Colleen O’Loughlin, Anthony Balistreri, Eric Chang, Doris Coto Villa, Joy Li, Aruna Varshney, Vanessa Jimenez, Jacqueline Pyle, Bryan Tsujimoto, Christopher Wellbrook, Christopher Vargas, Alex Duong, Nebat Ali, Sarah Matthews, Samantha Levinson, Sarah Woldemariam, Sami Khuri, Martina Bremer, Daryl Eggers, Noelle L’Etoile, Laura Miller Conrad, Miri Vanhoven

Faculty Publications, Chemistry

Predators and prey co-evolve, each maximizing their own fitness, but the effects of predator–prey interactions on cellular and molecular machinery are poorly understood. Here, we study this process using the predator Caenorhabditis elegans and the bacterial prey Streptomyces, which have evolved a powerful defense: the production of nematicides. We demonstrate that upon exposure to Streptomyces at their head or tail, nematodes display an escape response that is mediated by bacterially produced cues. Avoidance requires a predicted G-protein-coupled receptor, SRB-6, which is expressed in five types of amphid and phasmid chemosensory neurons. We establish that species of Streptomyces secrete dodecanoic acid, …

Thiamine Deficiency And Neurodegeneration: The Interplay Among Oxidative Stress, Endoplasmic Reticulum Stress, And Autophagy, Dexiang Liu, Zunji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Thiamine (vitamin B1) is an essential nutrient and indispensable for normal growth and development of the organism due to its multilateral participation in key biochemical and physiological processes. Humans must obtain thiamine from their diet since it is synthesized only in bacteria, fungi, and plants. Thiamine deficiency (TD) can result from inadequate intake, increased requirement, excessive deletion, and chronic alcohol consumption. TD affects multiple organ systems, including the cardiovascular, muscular, gastrointestinal, and central and peripheral nervous systems. In the brain, TD causes a cascade of events including mild impairment of oxidative metabolism, neuroinflammation, and neurodegeneration, which are commonly observed in …

Study Of Regulated Cell Death In Two Systems: Pd-1 In Natural Killer Cells And Rip3 In Neurons, Yu Huang

Dissertations & Theses (Open Access)

Cell death is not only an essential phenomenon in normal development and homeostasis, but also crucial in various pathologies. It is now clear that many types of cell death can be regulated by pharmacological or genetic interventions. These were largely achieved by identifying the molecular mechanisms underlying the regulated cell death (RCD). While in the immune system, RCD needs to be facilitated to help the clearance of pathogens and tumors, in healthy cells, especially the terminally differentiated neurons in the nervous system, it is more desirable to protect cells from dying due to stress under pathological conditions. Thus, understating the …

Modulation Of Spasticity By Trans-Spinal Direct Current Stimulation In Animals With Spinal Cord Injury, Wagdy Mekhael

Dissertations, Theses, and Capstone Projects

Central nervous system injuries usually produce motor impairments that are exacerbated by pathologically altered muscle tone. Abnormal muscle tone interferes with voluntary movement and is associated with loss of dexterity. Prior work in our laboratory demonstrated that 30-second trans-spinal direct current (DC) stimulation can temporarily modify muscle tone in anesthetized spastic mice after spinal cord injury (SCI). These experiments described DC-induced muscle tone responses to be polarity-dependent. That is, anodal stimulation (current passed from the lumbar spine to sciatic nerve) decreased muscle tone, and cathodal stimulation (current passed from the sciatic nerve to the lumbar spine) increased it. The present …

Modulation Of The Sodium/Potassium Atpase Function And Expression By Transcranial Direct Current Stimulation Of The Right Sensorimotor Cortex In Mice, Salim Bendaoud

Dissertations, Theses, and Capstone Projects

Direct current stimulation is used as a noninvasive therapeutic technique to enhance motor recovery following stroke, and to improve cognitive functions. This technique also showed promising results in the treatment of depression, schizophrenia, and multiple sclerosis. Transcranial direct current stimulation has been proven to cause a polarization (depolarization or hyperpolarization) of the target tissues depending on the polarity of the current and cell orientation. Because of the induced polarization, the spontaneous activity of the neurons is further affected. With exception to this electrophysiological effect, the overall biological mechanisms of transcranial direct current stimulation on the underlying tissues remain largely unknown. …

Distribution And Activation Of Catecholaminergic Neurons In The Brain Of Male Plainfin Midshipman Fish: Divergence In Behavior And Reproductive Phenotype, Zachary Ghahramani

Dissertations, Theses, and Capstone Projects

The plainfin midshipman fish, Porichthys notatus, provides an excellent opportunity for delimiting the influence of neurochemical content on vertebrate vocal behavior, in part because the production and recognition of social-acoustic signals is vital to their reproductive behavior. There are two distinct reproductive male morphs that follow divergent developmental trajectories with corresponding alternative reproductive tactics: type I males are the territorial/nesting morph that vocally court females during the summer breeding season while type II males do not court females, but instead sneak spawn in competition with type I males. Catecholaminergic neurons, which synthesize and release the neurotransmitters dopamine or noradrenaline, …

Phosphorylation Of Tau Protein At Thr175 Is A Toxic Event Associated With Neurodegeneration, Alexander Moszczynski

Electronic Thesis and Dissertation Repository

Aberrant phosphorylation and pathological deposition of the microtubule associated protein tau (tau protein) is associated with toxicity and cellular death in a number of neurodegenerative diseases (tauopathies). Specific phosphorylation sites are of interest in the processes leading to tau protein toxicity. One site of interest on tau protein is Thr¹⁷⁵ (pThr¹⁷⁵), which has been identified in diseased brain tissue from individuals with amyotrophic lateral sclerosis with cognitive impairment (ALSci) and Alzheimer’s disease. In vitro, pseudophosphorylation at this residue has been shown to induce the formation of pathological tau fibrils and, apoptotic cell death.

In my thesis, …

Amelioration Of Prenatal Alcohol Effects By Environmental Enrichment In A Mouse Model Of Fasd, Aniruddho Chokroborty-Hoque

Electronic Thesis and Dissertation Repository

Maternal alcohol consumption during pregnancy results in a spectrum of behavioural and cognitive deficits collectively known as Fetal Alcohol Spectrum Disorders (FASD). Currently, little is know about if and how the external environment may modulate these deficits. I have used C57BL/6 mice to study this interaction between prenatal alcohol exposure and the postnatal environment. Alcohol exposure during synaptogenesis produces high levels of anxiety-like traits and decreased memory performance. Alcohol-exposed mice (and matched unexposed controls) were put in 'environmentally-enriched' conditions of voluntary exercise, physical activities and cognitive stimulation to ascertain the effects of a positive postnatal environment. The results show that …

Investigating The Protective Effects Of Telomerase Reverse Transcriptase On Neuronal Metabolism And Resistance To Amyloid-Beta, Olivia Singh

Electronic Thesis and Dissertation Repository

Maintenance of telomere length during cell division is dependent on the catalytic subunit telomerase reverse transcriptase (TERT), which adds TTAGGG repeats to the ends of chromosomes to prevent telomere shortening during DNA replication. However, non-telomeric roles of TERT have emerged under oxidative stress whereby TERT translocates from the nucleus to the mitochondria and protects against mitochondrial dysfunction through a poorly defined mechanism. A major pathological feature of Alzheimer’s Disease (AD) is the progressive accumulation of amyloid-beta (Aβ) peptide within the cortex and hippocampus. Aβ can directly interfere with mitochondrial respiration and promote mitochondrial dysfunction, ROS production, and neuronal cell death. …

Pattern Recognition Receptors, Immune Proteins, And Nf-Κb Signaling Regulate Behaviors Associated With Aging Phenotypes, Nicholas W. Dekorver

Theses & Dissertations

The aging process is accompanied by functional impairments, including reduced locomotor function, fragmentation of active states, and alterations in energy balance. Our lab has demonstrated that immune proteins are increased in specific regions of the mouse brain that correlate with strain specific deficits. These immune proteins include toll-like receptors (Tlr), class I major histocompatibility complex proteins (MHC I), and complement proteins. There is an increasing appreciation for the role of immune proteins in neurodevelopment; however, their involvement in age-associated deficits is poorly understood. Here, we present data demonstrating that 1) activation of a specific immune receptor (Tlr2) leads to changes …

Inflammasome Activation By Methamphetamine Potentiates Lipopolysaccharide Stimulation Of Il-1Β Production In Microglia, Enquan Xu

Theses & Dissertations

Methamphetamine (Meth) is a psychostimulant drug that is widely abused all around the world. The administration of Meth causes a strong instant euphoria effect, and long-term of abuse is correlative of drug-dependence and neurotoxicity. The neuroimaging studies demonstrated that the long-term abuse of Meth is associated with the reduction of the dopamine transporter (DAT) and vesicular monoamine transporter (VMAT2) in the striatum. Neuroinflammation is well-accepted as an important mechanism underlying the Meth-induced neurotoxicity. The over-activated microglia were found both in Meth human abusers and animal models.

NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is the most predominant Nod-like …

Conditional Sox9 Ablation 30 Days After Spinal Cord Injury: Testing The Therapeutic Value Of A Successful Acute Strategy To Increase Neuroplasticity In A Model Of Chronic Spinal Cord Injury, Natalie M. Ossowski

Electronic Thesis and Dissertation Repository

Many individuals who have suffered from spinal cord injury (SCI) have longstanding damage. The molecular environment of the spinal cord is not permissive to axonal growth and neuroplasticity after injury is limited. Perineuronal nets containing chondroitin sulfate proteoglycans (CSPGs) are major inhibitors of axonal sprouting. Our laboratory has identified that the transcription factor SOX9 regulates a battery of genes involved in CSPG biosynthesis. Using Sox9 conditional knockout mice, we have shown that ablating Sox9 before injury decreases CSPG levels in the cord, increases reparative sprouting, and leads to improved locomotor recovery. However, it is unknown whether Sox9 ablation following SCI …

Prefrontal Cortex Dopamine Transmission Regulates Emotional Memory Processing And Morphine Reward Salience: Implications For Post-Traumatic Stress Disorder And Addiction Comorbidity, Jing Jing Li

Electronic Thesis and Dissertation Repository

Post-Traumatic Stress Disorder (PTSD) and addiction are strongly comorbid. However, the underlying neural mechanisms by which traumatic memory recall may increase addiction liability are poorly understood. The inability to suppress memory recall related to either stressful or rewarding, drug-related experiences may be an underlying neuropsychological feature capable of triggering both PTSD or addiction-related behaviours. Our previous research has shown that transmission through dopamine (DA) D₄ and D₁ receptor subtypes (D₄R, D₁R) within the prefrontal cortex (PFC) strongly modulates emotional memory acquisition and recall (Lauzon et al., 2009). Using olfactory fear conditioning and morphine conditioned …

Using The Suprachiasmatic Nucleus As A Model System To Assess Tolerance And Withdrawal To Alcohol, Jonathan Houghton Lindsay

Doctoral Dissertations

Alcohol abuse induces many disorders including depression, metabolic syndrome, and sleep disturbances. The strong link between alcohol abuse and sleep problems, along with the close connection between sleep and circadian rhythms, led us to investigate ethanol’s effects on the circadian clock. Previous work has shown that acute ethanol blocks photic phase shifts in vivo and glutamatergic phase shifts in vitro. However, neural systems become tolerant to ethanol across different timeframes. Despite both ethanol tolerance and ethanol withdrawal syndrome being listed as criteria for developing alcohol use disorders, little is known about how ethanol tolerance and withdrawal induced hyperexcitability develop and …

Modification Of Aplysia Feeding Network By L-Dopa And Dopamine-Dependent Learning, Curtis Neveu, Curtis L. Neveu

Dissertations & Theses (Open Access)

Dopamine (DA) is a ubiquitous neuromodulator of neuronal networks in the animal kingdom and has a well-established role in modulating motor behavior and encoding reward information. Although the effects of DA and DA-dependent learning at the behavioral and molecular levels are well-understood, many questions still remain concerning the effects of DA at the network level. DA-dependent learning effects on a neuronal circuit were examined by measuring the biophysical properties before and after in vitro operant conditioning (OC) of the feeding circuit of Aplysia. OC reduced the excitability of B4 and the B4-to-B51 synaptic connection, with a trend towards an …

Evolution Of Caffeine Biosynthetic Enzymes And Pathways In Flowering Plants, Ruiqi Huang

Dissertations

Convergent evolution generally refers to the independent evolution of similar biological function more than once in unrelated species. Caffeine is thought to have evolved by convergence, and is naturally produced through secondary metabolism in plants to defend against pathogen attack and insect feeding or to attract pollinators. The same caffeine biosynthetic pathway has been elucidated in Camellia (tea) and Coffea (coffee), in which xanthosine is sequentially methylated to caffeine via 7-methylxanthine and theobromine. However, although the same catalysis pathway is used, different (paralogous) enzymes in the SAMT/BAMT/theobromine synthase (SABATH) multigene family are used in the two species. In my dissertation, …

Chaperoning Ef Hands That Shape Calcium Response: Ncald, Hpca And S100b, Jingyi Zhang

Graduate School of Biomedical Sciences Theses and Dissertations

All organisms have an internal clock with a defined period between repetitions of activities. The period for circadian clock in human is 24.5 hours, while in mouse and rat, it is 23.5 hours. However, all organisms are forced to be in synchronization with their environment. A major environmental force that resets the internal clock to 24 hours is light. This phenomenon is defined as “light entrainment” or “phase-setting”. It is unclear how this entrainment process occurs. Studies from this laboratory indicate a role for two neuronal calcium sensor proteins: Neurocalcin  (NCALD) and S100B. For these two genes, mRNA as …

Elucidating Mechanisms Of Protein Aggregation In Alzheimer’S Disease Using Antibody-Based Strategies., Benjamin A. Colvin

Dissertations

Alzheimer’s Disease (AD) is a devastating neurodegenerative disorder. There are two characteristic histopathological hallmarks in the brain: senile plaques and neurofibrillary tangles, composed of insoluble aggregates of the amyloids Amyloid-β (Aβ) and tau protein, respectively. These diagnostic markers, though distinctive, are not apparent effectors of AD pathology. Evidence has mounted suggesting smaller soluble aggregates (oligomers) of Aβ or tau are the true drivers of disease progression. This dissertation presents several amyloid biophysics projects. Aggregate biophysical parameters such as weight, shape, and conformation were measured using a range of methodologies, including Multiangle Light Scattering, Dynamic Light Scattering, UV-Circular Dichroism, UV-Fluorescence, Scanning …

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers, Fei Tang, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against …

Osteopontin Facilitates West Nile Virus Neuroinvasion Via Neutrophil “Trojan Horse” Transport, Amber M. Paul, Dhiraj Acharya, Laurel Duty, E. Ashley Thompson, Linda Le, Dobrivoje S. Stokic, A. Arturo Leis, Fengwei Bai

Publications

West Nile virus (WNV) can cause severe human neurological diseases including encephalitis and meningitis. The mechanisms by which WNV enters the central nervous system (CNS) and host factors that are involved in WNV neuroinvasion are not completely understood. The proinflammatory chemokine osteopontin (OPN) is induced in multiple neuroinflammatory diseases and is responsible for leukocyte recruitment to sites of its expression. In this study, we found that WNV infection induced OPN expression in both human and mouse cells. Interestingly, WNV-infected OPN deficient (Opn−/−) mice exhibited a higher survival rate (70%) than wild type (WT) control mice (30%), suggesting OPN plays a …