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Quantifying The Spectrum Of Depression, Octavious Bishop

Walden Dissertations and Doctoral Studies

Walden University

College of Social and Behavioral Sciences

This is to certify that the doctoral dissertation by

Octavious Bishop

has been found to be complete and satisfactory in all respects,

and that any and all revisions required by

the review committee have been made.

Review Committee

Dr. Thomas Edman, Committee Chairperson, Psychology Faculty

Dr. Ricardo Thomas, Committee Member, Psychology Faculty

Dr. Joanna Bissell-Havran, University Reviewer, Psychology Faculty

Chief Academic Officer

Eric Riedel, Ph.D.

Quantifying the Spectrum of Depression

by

Octavious Bishop

MA, University of Texas at Austin, 2008

BS, University of Texas at Austin, 2001

Dissertation Submitted in Partial Fulfillment …

Heteromeric Assemblies Of Glua3 Flip And Flop Shows Differences In Their Channel Opening Kinetics, Nicholas Karl

Legacy Theses & Dissertations (2009 - 2024)

Prior studies of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, including that of GluA3 AMPA receptor subunit, have shown that alternative mRNA splicing, which generates flip and flop variants with different amino acid sequences, gives rise to functional differences between the two variants. The goal of this MS thesis is to investigate the basic gating properties of the heteromeric complex channels formed from GluA2R/GluA3 AMPA receptor subunits and the different variants between the two subunits. The hypothesis to be tested is whether different GluA3 variants affect the channel gating properties when each of the variants is in a complex with the Q/R-site edited …

A Behavioral Mechanistic Investigation Of The Role Of 5-Ht1a Receptors In The Mediation Of Rat Maternal Behavior, Xiaonan Li, Xiaojing Ding, Ruiyong Wu, Leilei Chen, Jun Gao, Gang Hu, Ming Li

Department of Psychology: Faculty Publications

Previous work suggests that 5-HT_1A receptors play a special role in rodent maternal aggression, but not in other aspects of maternal care (e.g. pup retrieval and nest building). The present study re-assessed the basic effects of 5-HT_1A activation or blockade on various maternal responses in postpartum female rats. We also examined the possible behavioral mechanisms underlying the maternal effects of 5-HT_1A. Sprague–Dawley mother rats were injected with a 5-HT_1A agonist 8-OH-DPAT (0.1, 0.5 or 1.0 mg/kg, sc), a 5-HT_1A antagonist WAY-101405 (0.1, 0.5 or 1.0 mg/kg, sc) or 0.9% saline solution on postpartum days …

Signaling Through Homomeric And Heteromeric Cannabinoid Cb1 Receptors, Guoqing Xiang

Theses and Dissertations

Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the …

Decoding The Signaling Of The D2r-2ar Heteromer: Relevance To Schizophrenia, Miao Huang

Theses and Dissertations

Schizophrenia is a severe mental disorder affecting ~1% of world population. Two G protein coupled receptors (GPCRs): Gi-coupled dopamine D2 receptor (D₂R), and Gq-coupled serotonin 2A receptor (2AR), are targeted by the typical and atypical antipsychotic drugs to treat schizophrenia. These two receptors have been shown to co-localize in brain regions relevant to schizophrenia, including the ventral tegmental area (VTA), striatum, and prefrontal cortex (PFC). Studies in our lab characterized the integrated signaling of the D₂R-2AR heteromer and found that both the Gi activity of D₂R and the Gq activity of 2AR were potentiated …

Chronic Clozapine Treatment Impairs Functional Activation Of Metabotropic Glutamate Receptor 2 Via An Hdac2-Depedent Mechanism, Travis M. Cuddy

Theses and Dissertations

Schizophrenia is a chronic mental disorder affecting millions worldwide. It has no known cure. Current pharmaceutical treatments have shown efficacy in only one of the three symptom clusters of schizophrenia, providing little or no benefit in the other two. Furthermore, the current standard-of-care drugs, known as atypical antipsychotics, carry risks of severe side effects affecting multiple body systems. Most patients opt to discontinue drug therapy within two years of initiation due to lack of efficacy and/or preponderance of adverse effects. Previous findings have shown that chronic usage of atypical antipsychotics causes a 5-HT_2A-dependent upregulation of histone deacetylase 2 …

Brain Energy Homeostasis And The Regulation Of N-Acetyl-Aspartate Metabolism In Development And Disease, Samantha Zaroff

Graduate School of Biomedical Sciences Theses and Dissertations

N-acetylaspartate (NAA) is a non-invasive clinical marker of neuronal metabolic integrity because of its strong proton magnetic resonance spectroscopy (H-MRS) peak and direct correlation with energetic integrity. Specifically, NAA is used to track the progression of neurodegenerative diseases due to the characteristic reduction of whole brain levels of NAA which occur simultaneously with reduced glucose utilization and mitochondrial dysfunction, but prior to the onset of disease specific pathology. However, NAA will also significantly increase simultaneously with energetic integrity during periods of recovery or remission in applicable disorders, such as traumatic brain injuries. Unfortunately, it remains enigmatic exactly why NAA is …

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

Dissertations and Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …

Pharmacological Antagonism And The Olfactory Code, Mihwa Na

Dissertations, Theses, and Capstone Projects

Mammals can detect and discriminate uncountable odors through their odorant receptors. To accommodate the countless and diverse odors, exceptionally large numbers of odorant receptor (OR) genes are expressed in mammals. In addition, the mammals utilize a combinatorial code, where an odorant molecule can activate multiple ORs; an OR also responds to a set of multiple odorants. In nature, an odor is often a complex mixture of multiple odorant molecules. The combination of the ORs activated by each constituent generates the unique olfactory code for the particular odor.

Some odorants can antagonize select ORs, as discussed in Chapter 1. An antagonist …

Regulation Of The Amyloid Precursor Protein By Prostaglandin J2, A Mediator Of Inflammation: Relevance To Alzheimer’S Disease, Teneka L. Jean-Louis

Dissertations, Theses, and Capstone Projects

Inflammation plays a major role in Alzheimer’s disease (AD). Investigating how specific mediators of inflammation contribute to neurodegeneration in AD is crucial. Our studies focused on cyclooxygenases, which are key enzymes in inflammation and highly relevant to AD. Cyclooxygenases (COX -1, constitutive; COX-2, inducible) have emerged as important determinants of AD pathogenesis and progression. COX-2 is highly induced in AD, correlating with AD severity, and COX-1 is also involved in AD. Cyclooxygenases are the rate-limiting enzymes that convert arachidonic acid into prostaglandins (PGs), the principal mediators of CNS neuroinflammation.

The overall GOAL of these studies was to address the mechanisms …

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, …

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 …

Investigating The Synergistic Effects Of Cisplatin And Two Curcuminoid Compounds On Cancer, Denis Hodzic

Mahurin Honors College Capstone Experience/Thesis Projects

Cisplatin is an anti-cancer drug effective against several cancers which can produce the serious side-effect of hearing loss. Curcumin, a natural plant compound, can increase the activity of cisplatin against cancer and counteract cisplatin’s effect against hearing. Because curcumin exhibits poor bioavailability, there is considerable interest in developing synthetic curcumin analogs (curcuminoids) that are more soluble and which retain anti-cancer activity and otoprotective function. This study investigated whether two curcuminoids, EF-24 and CLEFMA, increase the cytotoxic and ototoxic effects of cisplatin against the lung cancer cell line, A549, and the colorectal cancer cell line, Caco2. Cytotoxicity was measured by using …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Sivasai Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Selected Works Temporary Series

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Microarray Analysis Of Aging-Associated Immune System Alterations In The Rostral Ventrolateral Medulla Of F344 Rats, Balivada, Chanran Ganta, Yongqing Zhang, Hitesh Pawar, Richard Ortiz, Kevin Becker, Arshad Khan, Michael Kenney

Departmental Papers (Biology)

The rostral ventrolateral medulla (RVLM) is an area of the brain stem that contains diverse neural substrates that are involved in systems critical for physiological function. There is evidence that aging affects some neural substrates within the RVLM, although age-related changes in RVLM molecular mechanisms are not well established. The goal of the present study was to characterize the transcriptomic profile of the aging RVLM and to test the hypothesis that aging is associated with altered gene expression in the RVLM, with an emphasis on immune system associated gene transcripts. RVLM tissue punches from young, middle-aged, and aged F344 rats …

Igf-1 Mediated Neurogenesis Involves A Novel Rit1/Akt/Sox2 Cascade, Sajad Mir, Weikang Cai, Shaun W. Carlson, Kathryn E. Saatman, Douglas A. Andres

Molecular and Cellular Biochemistry Faculty Publications

Insulin-like growth factor 1 (IGF-1) is known to have diverse effects on brain structure and function, including the promotion of stem cell proliferation and neurogenesis in the adult dentate gyrus. However, the intracellular pathways downstream of the IGF-1 receptor that contribute to these diverse physiological actions remain relatively uncharacterized. Here, we demonstrate that the Ras-related GTPase, RIT1, plays a critical role in IGF-1-dependent neurogenesis. Studies in hippocampal neuronal precursor cells (HNPCs) demonstrate that IGF-1 stimulates a RIT1-dependent increase in Sox2 levels, resulting in pro-neural gene expression and increased cellular proliferation. In this novel cascade, RIT1 stimulates Akt-dependent phosphorylation of …

Oxidation Of Substituted Catechols At The Air-Water Interface: Production Of Carboxylic Acids, Quinones, And Polyphenols, Elizabeth A. Pillar, Marcelo I. Guzman

Chemistry Faculty Publications

Anthropogenic activities contribute benzene, toluene, and anisole to the environment, which in the atmosphere are converted into the respective phenols, cresols, and methoxyphenols by fast gas-phase reaction with hydroxyl radicals (HO(•)). Further processing of the latter species by HO(•) decreases their vapor pressure as a second hydroxyl group is incorporated to accelerate their oxidative aging at interfaces and in aqueous particles. This work shows how catechol, pyrogallol, 3-methylcatechol, 4-methylcatechol, and 3-methoxycatechol (all proxies for oxygenated aromatics derived from benzene, toluene, and anisole) react at the air-water interface with increasing O3(g) during τc ≈ 1 μs contact time and contrasts their …

Development Of Ad Like Symptoms Following Co-Administration Of Alcl3 And D-Gal In Rats: A Neurochemical, Biochemical And Behavioural Study, Laraib Liaquat, Saara Muddasir, Sadia Adir, Zehra Batool, Saima Khaliq, Saiqa Tabassum, Shaista Emad, Syeda Madiha, Sidrah Shahzad, Saida Haider

Department of Biological & Biomedical Sciences

Alzheimer's disease (AD) is an age-related neurodegenerative disorder associated with neurochemical and neurobehavioural alterations. Aluminium (Al) is considered as a contributing factor in the etiology of several neurodegenerative disorders like AD. D-galactose (D-gal) is a physiological nutrient but over supply induces some neurochemical and biochemical changes that exacerbate natural aging process. In this study, we aimed to develop AD animal model by co-administration of Al and D-gal in rats. Male albino Wistar rats were intraperitoneally injected with AlCl₃ and D-gal at a dose of 150mg/kg and 300mg/kg respectively for one week. After one week rats were subjected to behavioural …

Calcium's Role As Nuanced Modulator Of Cellular Physiology In The Brain, Hilaree N. Frazier, Shaniya Maimaiti, Katie L. Anderson, Lawrence D. Brewer, John C. Gant, Nada M. Porter, Olivier Thibault

Pharmacology and Nutritional Sciences Faculty Publications

Neuroscientists studying normal brain aging, spinal cord injury, Alzheimer’s disease (AD) and other neurodegenerative diseases have focused considerable effort on carefully characterizing intracellular perturbations in calcium dynamics or levels. At the cellular level, calcium is known for controlling life and death and orchestrating most events in between. For many years, intracellular calcium has been recognized as an essential ion associated with nearly all cellular functions from cell growth to degeneration. Often the emphasis is on the negative impact of calcium dysregulation and the typical worse-case-scenario leading inevitably to cell death. However, even high amplitude calcium transients, when executed acutely can …

The Association Of Serum Levels Of Brain-Derived Neurotrophic Factor With The Occurrence Of And Recovery From Delirium In Older Medical Inpatients, John Williams, Karen Finn, Vincent Melvin, David Meagher, Geraldine Mccarthy, Dimitrios Adamis

Department of Biological Sciences Publications

Limited studies of the association between BDNF levels and delirium have given inconclusive results. This prospective, longitudinal study examined the relationship between BDNF levels and the occurrence of and recovery from delirium. Participants were assessed twice weekly using MoCA, DRS-R98, and APACHE II scales. BDNF levels were estimated using an ELISA method. Delirium was defined with DRS-R98 (score > 16) and recovery from delirium as ≥2 consecutive assessments without delirium prior to discharge. We identified no difference in BDNF levels between those with and without delirium. Excluding those who never developed delirium (), we examined the association of BDNF levels and …

Ck2—An Emerging Target For Neurological And Psychiatric Disorders, Julia Castello, Andre Ragnauth, Eitan Friedman, Heike Rebholz

Publications and Research

Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full …

Code For "Noise-Enhanced Coding In Phasic Neuron Spike Trains", Cheng Ly, Brent D. Doiron

Statistical Sciences and Operations Research Data

This zip file contains Matlab scripts and ode (XPP) files to calculate the statistics of the models in "Noise-Enhanced Coding in Phasic Neuron Spike Trains". This article is published in PLoS ONE.

Alpha-Synuclein: Insight Into The Hallmark Of Parkinson's Disease As A Target For Quantitative Molecular Diagnostics And Therapeutics, Baggio A. Evangelista

Honors Undergraduate Theses

Parkinson’s disease (PD) is the second-most common neurodegenerative disease after Alzheimer’s disease. With 500,000 individuals currently living with Parkinson’s and nearly 60,000 new cases diagnosed each year, this disease causes significant financial burden on the healthcare system - amassing to annual expenditures totaling 200 billion dollars; predicted to increase through 2050. The disease phenotype is characterized by a combination of a resting tremor, bradykinesia, muscular rigidity, and depression due to dopaminergic neuronal death in the midbrain. The cause of the neurotoxicity has been largely discussed, with strong evidence suggesting that the protein, alpha-Synuclein, is a key factor. Under native conditions, …

Transposon-Mediated Stable Suppression Of Gene Expression In The Developing Chick Retina, Masaru Nakamoto, Chizu Nakamoto

Biology Faculty Publications

The embryonic chick has long been a favorite model system for in vivo studies of vertebrate development. However, a major technical limitation of the chick embryo has been the lack of efficient loss-of-function approaches for analyses of gene functions. Here, we describe a methodology in which a transgene encoding artificial microRNA sequences is introduced into embryonic chick retinal cells by in ovo electroporation and integrated into the genome using the Tol2 transposon system. We show that this methodology can induce potent and stable suppression of gene expression. This technique therefore provides a rapid and robust loss-of-function approach for studies of …

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 …

Effects Of Asiatic Acid On Neurite Outgrowth In Neuro-2a Cells, Aishah Asiri

Masters Theses

Recently, medicinal plants from ancient Ayurvedic medicine have provided clues to the discovery of novel therapeutics for various diseases. In Ayurvedic medicine, a common Indian plant, Centella asiatica is highly regarded as a "rasayana" or nerve tonic. The Centella extract is used to ward off age-related dementia and to increase memory and intelligence. The mechanism by which Centella improves memory and learning and reduces the risk of dementia is unclear.

We recently tested the effects of asiatic acid, the main active component of Centella, on neuronal growth. We hypothesized that asiatic acid will promote neuronal growth and neurite network …

A Laser-Pulse Photolysis Study Of The Mechanism Of Potentiation Of The Glua2qflip Ampa Receptors By Cx546, Yu-Chuan Shen

Legacy Theses & Dissertations (2009 - 2024)

Insufficient activity of the α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate ion channels is involved in neurological disorders and developmental problems, such as schizophrenia, one of the most serious psychiatric diseases. Use of regulatory agents to enhance AMPA receptor activity under the circumstance has been shown therapeutically beneficial. Specifically, small-molecule compounds generally termed as potentiators or positive modulators of AMPA receptors have long been pursued as drug candidates for a potential treatment of these neurological disorders and diseases. The goal of my MS thesis work is to investigate the mechanism of potentiation on AMPA receptor by a classic potentiator known as CX546. The …

Retinal Disease Modeling And Drug Screening Using Stem Cell Derived Retinal Pigment Epithelium, Janmeet Singh Saini

Legacy Theses & Dissertations (2009 - 2024)

The eye is an intricate organ, possessing sensory receptors in the retina that are involved in visual perception. The retina consists primarily of the neural layer, referred to as the neural retina, and the pigmented layer, referred to as the retinal pigment epithelium (RPE). The neural retina and RPE develop and mature in a coordinated manner, and depend on each other for survival. In a mature healthy retina, the retinal photoreceptor outer segments interdigitate with the RPE monolayer, and they co-exchange key supportive factors. RPE cells are indispensable for the health of the retina as they are involved in a …

A Rare Case Of Erythema Elevatum Diutinum Presenting As Diffuse Neuropathy, G H. Nguyen, E L. Guo, D Norris

Faculty, Staff and Students Publications

No abstract provided.