Cholinergic Control Of Cortical Circuit Activity,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Cholinergic Control Of Cortical Circuit Activity, Rajan Dasgupta
Dissertations and Theses (Open Access)
Cholinergic neurons of the basal forebrain send extensive projections to all regions of the neocortex and are critically involved in a diverse array of cognitive functions, including sensation, attention and learning. Cholinergic signaling also plays a crucial role in the moment-to-moment control of ongoing cortical state transitions that occur during periods of wakefulness. Yet, the underlying circuit mechanisms of synaptic cholinergic function in the neocortex remain unclear. Moreover, acetylcholine continues to be widely viewed as a slow and diffuse neuromodulator, despite the preponderance of in vivo evidence demonstrating rapid cholinergic function. In this study, we used a combination of optogenetics …
Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus.,
2018
University of Louisville
Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus., Guela Sokhadze
Electronic Theses and Dissertations
Cholinergic signaling plays a vital role in modulating the flow of sensory information through thalamic circuits in a state-dependent manner. In the dorsal lateral geniculate nucleus (dLGN), the thalamic visual relay, release of acetylcholine (ACh) contributes to enhanced thalamocortical transfer of retinal signal during behavioral states of arousal, wakefulness, and sleep/wake transitions. Moreover, ACh modulates activity of the thalamic reticular nucleus (TRN), a structure which provides inhibitory input to dLGN. While several cholinergic nuclei have been shown to innervate dLGN and TRN, it is unclear how projections from each area are organized. Furthermore, little is known of how or when …
The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy,
2018
The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe
Dissertations and Theses (Open Access)
In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral …
Modeling And Mapping Addiction In The Zebrafish, Danio Rerio,
2018
Kennesaw State University
Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa
Master of Science in Integrative Biology Theses
Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …
Endocytosis And The Nitric Oxide-Dependent Release Of Chloride,
2018
Louisiana State University and Agricultural and Mechanical College
Endocytosis And The Nitric Oxide-Dependent Release Of Chloride, Vernon K. Dunn Jr
LSU Doctoral Dissertations
Understanding the regulation of retinal synapses is a key step in elucidating the processing of information in the retina. Our lab has previously shown that nitric oxide (NO) can alter the synaptic response properties of amacrine cells by releasing Cl- from internal acidic compartments. This alteration in the Cl- gradient brings about a positive shift in the reversal potential of the GABA-gated current, which can convert inhibitory synapses into excitatory synapses. Recently, we have shown that the cystic fibrosis transmembrane regulator (CFTR) Cl- channel is involved in the Cl- release. Here, we test the hypothesis that (acidic) synaptic vesicles are …
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees,
2018
University of Texas at El Paso
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins
Selected Works Temporary Series
This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees,
2018
University of Texas at El Paso
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Khan, Alice Grant, Anais Martinez, Gully Burns, Brendan Thatcher, Vishwanath Anekonda, Benjamin Thompson, Zachary Roberts, Daniel Moralejo, James Blevins
Departmental Papers (Biology)
This article, which includes novel unpublished data along with commentary and analysis,focuses on approaches to link transcriptomic, proteomic, and peptidomic datasets mined frombrain tissue to the original locations within the brain that they are derived from using digital atlasmapping techniques. We use, as an example, the transcriptomic, proteomic and peptidomicanalyses conducted in the mammalian hypothalamus. Following a brief historical overview, wehighlight studies that have mined biochemical and molecular information from the hypothalamusand then lay out a strategy for how these data can be linked spatially to the mapped locations in acanonical brain atlas where the data come from, thereby allowing …
Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity,
2018
New York University
Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity, María E. Solesio, Pablo M. Peixoto, Ludovic Debure, Stephen M. Madamba, Mony J. De Leon, Thomas Wisniewski, Evgeny V. Pavlov, Silvia Fossati
Publications and Research
Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer’s disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid b (Ab)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Ab, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Ab, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than …
Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation,
2018
Washington University in St. Louis
Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas
McKelvey School of Engineering Graduate Student Theses & Dissertations
Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor protein (APP), …
Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment,
2018
Georgia Southern University - Armstrong
Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment, Robert A. Mans, Kyle D. Hinton, Amanda E. Rumer, Kourtnei A. Zellner, Emily A. Blankenship, Lia M. Kerkes, Michael J. Hamilton, Theresa R. Reilly, Cicely H. Payne
Georgia Journal of Science
Zebrafish are a powerful research tool in the field of neuroscience, offering several logistical and physiological advantages over rodents as a research model. However, the molecular dynamics of this model organism, especially with regards to learning and memory, are scarcely known. The current study explored the zebrafish brain for the presence of a protein bearing a similar function to the activity-regulated, cytoskeleton-associated protein (Arc), a critical player in synaptic plasticity. The adult zebrafish brain was found to express a protein with immunoreactivity against the anti-Arc antibody H-300. Immunoreactivity was detected ubiquitously, especially in areas known as adult progenitor cell zones. …
Characterizing Tau In The Nucleus,
2018
James Madison University
Characterizing Tau In The Nucleus, Shaw Grindle Camphire, Madeline Louise Henwood
Senior Honors Projects, 2010-2019
A hallmark of Alzheimer’s Disease (AD) is the aggregation of hyperphosphorylated tau protein into neurofibrillary tangles. Tau localizes to both the cytoplasm and the nucleus of neuronal cells; however, its nuclear role has not been fully defined. Tau has recently been shown to bind to purine-pyrimidine (R/Y) repeats in DNA and stabilize them into Z-DNA. Evidence from our lab suggests that the binding of tau to R/Y repeats causes transcriptional changes of the NOS1 gene. Six major isoforms of tau exist in neurons. These isoforms fall into two groups, denoted as 3R tau and 4R tau, and are found at …
T Cell Mediated Cytotoxicity In The Mptp Mouse Model Of Parkinson's Disease,
2018
University of Nebraska Medical Center
T Cell Mediated Cytotoxicity In The Mptp Mouse Model Of Parkinson's Disease, Rebecca A. Wilshusen
Theses & Dissertations
Increasing evidence suggests that neurotoxic inflammatory activities affect the pathogenesis and progression of PD. Neuroinflammatory processes also produce oxidized and modified self-central nervous system (CNS) proteins which lead to dysfunction, mis-folding, aggregation, and retention of those oxidized products. In PD, nitrated α-synuclein (N-α-syn) is found aggregated within the cytoplasm and Lewy bodies of dopaminergic neurons within the substantia nigra and is released to the extraneuronal environment by dying and damaged neurons. Previous studies have shown that after 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) intoxication, adoptive transfer of effector T cells (Teff) exacerbates microglial-mediated neuroinflammation and amplifies dopaminergic neurodegeneration with accelerated and prolonged …
Functional And Structural Impact Of The Loss Of The Leucine-Rich Repeat Protein Lrit1 In The Mouse Retina.,
2018
University of Louisville
Functional And Structural Impact Of The Loss Of The Leucine-Rich Repeat Protein Lrit1 In The Mouse Retina., Catherine Ann Cobb
Electronic Theses and Dissertations
Mutations in genes encoding the leucine-rich repeat (LRR) proteins nyctalopin and LRIT3 lead to complete congenital stationary night blindness because they are critical to depolarizing bipolar cell function in the retina. LRIT3 has two closely related family members, LRIT1 and LRIT2. In silico analyses of publicly available RNA-Seq data showed that Lrit1 was highly expressed in the retina. Here I describe the expression pattern and impact of loss of LRIT1 on retinal function. To enable these studies, we used CRISPR/Cas9 technology to create an Lrit1-/- mouse line. Retinal morphology and morphometry analyses showed no gross changes in retinal structure …
Is Concussion-Related Sleep Disturbance Present After Return To Play In College Athletes?,
2018
University of Connecticut
Is Concussion-Related Sleep Disturbance Present After Return To Play In College Athletes?, Alexander Gallaer
Honors Scholar Theses
As one of the most commonly experienced symptoms, the ramifications of sleep disruption as a result of concussion are potentially great, yet widely unexplored. Particularly troublesome is murky data regarding the length of sleep disruption following a concussion. By analyzing self-reported sleep data via the Pittsburgh Sleep Quality Index, this study seeks to investigate potential differences in sleep quality between injured college athletes 40 days after they have been cleared to play and matched controls. Data was analyzed using ANOVA analysis as well as Pearson correlation. No significant differences were found in sleep quality between groups, nor was there a …
The Role Of Oxidative Stress And Signal Transduction In Chemotherapy-Mediated Cognitive Impairment In The Menopause Rat Model,
2018
CUNY Graduate Center
The Role Of Oxidative Stress And Signal Transduction In Chemotherapy-Mediated Cognitive Impairment In The Menopause Rat Model, Ciara Bagnall
Dissertations, Theses, and Capstone Projects
Systemic chemotherapy treatment is associated with long-term cognitive impairment in breast cancer survivors. While many studies have established the forms of cognition and corresponding regions in the brain most affected, very little is revealed about the potential molecular mechanisms that mediate these changes. The effects of systemic treatment on the brain is likely attributed to many different mechanisms including oxidative stress and immune dysregulation. Earlier studies from our lab have investigated the effects of the chemotherapy cocktail doxorubicin and cyclophosphamide (AC Chemotherapy) in an ovariectomized menopause animal model of ‘chemo brain’ (Salas-Ramirez et al., 2015). We observed that animals injected …
Non-Canonical Activation Of Creb/Crh-1 Mediates Neuroprotection In A Caenorhabditis Elegans Model Of Excitotoxic Necrosis,
2018
CUNY Graduate Center
Non-Canonical Activation Of Creb/Crh-1 Mediates Neuroprotection In A Caenorhabditis Elegans Model Of Excitotoxic Necrosis, K. Genevieve Feldmann
Dissertations, Theses, and Capstone Projects
Excitotoxicity, which is a major cause of neurodegeneration in brain ischemia, can also activate neuroprotective pathways. A frequently suggested neuroprotective cascade involves the activation of the transcription factor CREB by its phosphorylation, but on its own this mode of CREB activation is promiscuous. We aim to elucidate the specific mechanism of CREB activation in excitotoxicity-induced neuroprotection, focusing on three suggested models: CREB phosphorylation by calcium-activated kinases in the cytoplasm or nucleus, and the activation of CREB by CRTC (an important cofactor). Using a C. elegans model of excitotoxicity, we demonstrate that CREB’s neuroprotective effect is mainly seen in neurons exposed …
Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities,
2018
Liberty University
Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin
Senior Honors Theses
The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …
A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model,
2018
East Tennessee State University
A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model, Muhammad Tukur Ameen
Electronic Theses and Dissertations
Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B2, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the …
Examining The Appropriate Recovery Interval Following Maximal Exertion For Baseline Computerized Neurocognitive Testing (Cnt),
2018
University of Arkansas, Fayetteville
Examining The Appropriate Recovery Interval Following Maximal Exertion For Baseline Computerized Neurocognitive Testing (Cnt), Samantha Mohler
Graduate Theses and Dissertations
Background: Computerized neurocognitive testing is part of the recommended multi-faceted approach to SRC assessment. Prior research has suggested that maximal exertion negatively effects CNT test scores. Purpose: To identify the appropriate timing of the administration of CNT following maximal exertion in healthy college-aged students. Study Design: Random cross-over, repeated measures design. Methods: Participants will be administered CNT on four different visits, with at least one week between administrations. A VO2 max treadmill test will be performed before CNT administration during three of the four trials. Following the VO2 max test, participants will rest for <2 minutes (immediate), 10-minutes, or 20-minutes before taking CNT. The fourth trial, without maximal exertion preceding CNT administration, will serve as the control. All trials will be randomly-counterbalanced to negate practice effects. RESULTS: There was a significant within-subjects effect for prescribed post-exertion recovery intervals on total symptom scores (Wilks λ = .62, F [3, 23] = 4.64, p = .01, η2= .38). Total symptom scores were significantly higher at the immediate (p < .002), 10-minutes (p = .018), and 20-minutes (p = .011) post-exertion recovery intervals compared to baseline. Additionally, a significantly positive within-subjects effect for prescribed post exertion recovery was observed for processing speed (p=.009, Wilks λ = .60, F [3, 27] = 5.9, η2 = .396). No significant effect was observed for visual memory (p = .07), verbal memory (p = .06), or reaction time (p = .40). CONCLUSION: Baseline symptom scores were negatively influenced processing speed was enhanced by maximal exertion. These changes continue to be elevated 20 minutes post-exertion. Moreover, cognitive performance was not significantly impaired following maximal exercise. To obtain more accurate baseline symptom scores, and allow processing speed composites to return to normal, sports medicine professionals should wait at least 20 minutes following maximal exertion before administering CNT.
Reconstitution Of Gabaergic Postsynapses In Host Cells,
2018
University of Connecticut
Reconstitution Of Gabaergic Postsynapses In Host Cells, Karthik Kanamalla
Honors Scholar Theses
Type A GABA receptors (GABAARs) can be found embedded in postsynaptic membranes or in a variety of extrasynaptic locations. Receptors with synaptic function are recruited to the postsynapse by submembranous scaffolds composed of gephyrin and collybistin (CB). This study was aimed at assessing whether the ability to interact with the scaffold differentiates synaptic from non-synaptic receptors. Using HEK293 cells as an expression system, and indirect immunofluorescence (IF), co-localization of extrasynaptic receptors α1β3δ and α4β3δ with the CB-gephyrin scaffold was assessed and compared with that of the synaptic receptor α1β3γ2. Results indicated that both extrasynaptic receptors were able to colocalize with …
