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Articles 1 - 30 of 30
Full-Text Articles in Life Sciences
Calcium Imaging Of Central Amygdala Activity After Fentanyl Escalation, Samantha Malone
Calcium Imaging Of Central Amygdala Activity After Fentanyl Escalation, Samantha Malone
Theses and Dissertations--Psychology
Evidence suggests that rats given long access (LgA) sessions to self-administer (SA) opioids escalate their intake, while also showing greater withdrawal severity and drug-induced reinstatement compared to rats maintained on short access (ShA) daily SA sessions. Little is known about the neural changes that occur during opioid escalation that may impact withdrawal and relapse. Past work examining opioid SA using ShA sessions in rodents has identified the central amygdala (CeA) as an area of interest that becomes hyperactive in acute withdrawal and may be involved in the incubation of craving that occurs after protracted withdrawal. However, these studies have not …
Development Of Fluorescence Based Approaches To Understand Astrocyte Biology In The Context Of Nicotine And Nicotinic Receptor Activity, Surya P. Aryal
Development Of Fluorescence Based Approaches To Understand Astrocyte Biology In The Context Of Nicotine And Nicotinic Receptor Activity, Surya P. Aryal
Theses and Dissertations--Chemistry
Smoking and tobacco use (STU) is a major global health problem and worldwide more than six million people die due to tobacco related diseases each year. Although majority of smokers try to quit smoking several times in their life, traditional therapeutic approaches, which focus only on neuronal cells, have a very low success rate. Understanding the effect of nicotine on glial cells, synaptic communication and blood vasculature in the brain can provide further insights on the neurobiology of substance abuse and can potentially help to design better therapeutic approaches. Glial cells are non-excitable cells in the brain which do not …
The Effect Of Calcium Ions On Mechanosensation And Neuronal Activity In Proprioceptive Neurons, Devan E. Atkins, Kimberly L. Bosh, Grace W. Breakfield, Sydney E. Daniels, Makayla J. Devore, Hailey E. Fite, Landys Z. Guo, Danielle K. J. Henry, Alana K. Kaffenberger, Katherine S. Manning, Tatum E. Mowery, Cecilia L. Pankau, Nyla Parker, Malina E. Serrano, Yamaan Shakhashiro, Hannah N. Tanner, Ruth. A. Ward, Aubrey H. Wehry, Robin L. Cooper
The Effect Of Calcium Ions On Mechanosensation And Neuronal Activity In Proprioceptive Neurons, Devan E. Atkins, Kimberly L. Bosh, Grace W. Breakfield, Sydney E. Daniels, Makayla J. Devore, Hailey E. Fite, Landys Z. Guo, Danielle K. J. Henry, Alana K. Kaffenberger, Katherine S. Manning, Tatum E. Mowery, Cecilia L. Pankau, Nyla Parker, Malina E. Serrano, Yamaan Shakhashiro, Hannah N. Tanner, Ruth. A. Ward, Aubrey H. Wehry, Robin L. Cooper
Biology Faculty Publications
Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by pharmacological, physiological and molecular identification. The chordotonal organs within insects and crustaceans offer a unique ability to investigate proprioceptive function. The effects of the extracellular environment on neuronal activity, as well as the function of associated SACs are easily accessible and viable in minimal saline for ease in experimentation. The effect of extracellular [Ca2+] on …
Astrocytes Rescue Neuronal Health After Cisplatin Treatment Through Mitochondrial Transfer., Krystal English, Krystal English
Astrocytes Rescue Neuronal Health After Cisplatin Treatment Through Mitochondrial Transfer., Krystal English, Krystal English
Dissertations & Theses (Open Access)
Abstract
Astrocytes rescue neuronal health after cisplatin treatment through mitochondrial transfer.
Author: Krystal English
Advisory Professor: Dr. Cobi J. Heijnen, Ph.D.
Chemotherapy-induced cognitive impairments are associated with neuronal mitochondrial dysfunction. Cisplatin, a commonly used chemotherapeutic, induces neuronal mitochondrial dysfunction in vivo and in vitro. Astrocytes are key players in supporting neuronal development, synaptogenesis, axonal growth, metabolism and, potentially, mitochondrial health. We tested the hypothesis that astrocytes transfer healthy mitochondria to neurons after cisplatin treatment to restore neuronal health.
We used an in vitro system in which astrocytes with Mito-mCherry-labeled mitochondria were co-cultured with primary cortical neurons or neuronal stem …
Quantitative Proteomics Reveal An Altered Pattern Of Protein Expression In Brain Tissue From Mice Lacking Gpr37 And Gpr37l1, Trang Kimberly Thu Nguyen, Eric B. Dammer, Sharon A. Owino, Michelle M. Giddens, Nora S. Madaras, Duc M. Duong, Nicholas T. Seyfried, Randy A. Hall
Quantitative Proteomics Reveal An Altered Pattern Of Protein Expression In Brain Tissue From Mice Lacking Gpr37 And Gpr37l1, Trang Kimberly Thu Nguyen, Eric B. Dammer, Sharon A. Owino, Michelle M. Giddens, Nora S. Madaras, Duc M. Duong, Nicholas T. Seyfried, Randy A. Hall
Neuroscience: Faculty Publications
GPR37 and GPR37L1 are glia-enriched G protein-coupled receptors that have been implicated in several neurological and neurodegenerative diseases. To gain insight into the potential molecular mechanisms by which GPR37 and GPR37L1 regulate cellular physiology, proteomic analyses of whole mouse brain tissue from wild-type (WT) versus GPR37/GPR37L1 double knockout (DKO) mice were performed in order to identify proteins regulated by the absence versus presence of these receptors (data are available via ProteomeXchange with identifier PXD015202). These analyses revealed a number of proteins that were significantly increased or decreased by the absence of GPR37 and GPR37L1. One of the most decreased proteins …
Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast
Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast
Senior Honors Theses
This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …
Mechanisms Of Calcium-Dependent Neurotransmission In Photoreceptors, Justin J. Grassmeyer
Mechanisms Of Calcium-Dependent Neurotransmission In Photoreceptors, Justin J. Grassmeyer
Theses & Dissertations
Rod and cone photoreceptors initiate vision by transforming light into graded membrane voltage changes that in turn dictate the rate of continuous Ca2+-dependent neurotransmission to postsynaptic neurons. Continuous release relies on synaptic ribbons at photoreceptor active zones, which organize exocytotic proteins and deliver vesicles to release sites near voltage-gated Ca2+ channels. Individual cones possess multiple ribbon synapses at which they contact postsynaptic neurons. We examined heterogeneity in signaling at individual ribbon synapses in salamander cones by measuring the voltage dependence of Ca2+ currents (ICa) and Ca2+ influx at individual ribbon release sites. Ca …
Fk506-Binding Protein 12.6/1b, A Negative Regulator Of [Ca2+], Rescues Memory And Restores Genomic Regulation In The Hippocampus Of Aging Rats, John C. Gant, Eric M. Blalock, Kuey-Chu Chen, Inga Kadish, Olivier Thibault, Nada M. Porter, Philip W. Landfield
Fk506-Binding Protein 12.6/1b, A Negative Regulator Of [Ca2+], Rescues Memory And Restores Genomic Regulation In The Hippocampus Of Aging Rats, John C. Gant, Eric M. Blalock, Kuey-Chu Chen, Inga Kadish, Olivier Thibault, Nada M. Porter, Philip W. Landfield
Pharmacology and Nutritional Sciences Faculty Publications
Hippocampal overexpression of FK506-binding protein 12.6/1b (FKBP1b), a negative regulator of ryanodine receptor Ca2+ release, reverses aging-induced memory impairment and neuronal Ca2+ dysregulation. Here, we tested the hypothesis that FKBP1b also can protect downstream transcriptional networks from aging-induced dysregulation. We gave hippocampal microinjections of FKBP1b-expressing viral vector to male rats at either 13 months of age (long-term, LT) or 19 months of age (short-term, ST) and tested memory performance in the Morris water maze at 21 months of age. Aged rats treated ST or LT with FKBP1b substantially outperformed age-matched vector controls and performed similarly …
Mechanisms Underlying Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Medial Prefrontal Cortex, Emily K. Stephens, Arielle L. Baker, Allan T. Gulledge
Mechanisms Underlying Serotonergic Excitation Of Callosal Projection Neurons In The Mouse Medial Prefrontal Cortex, Emily K. Stephens, Arielle L. Baker, Allan T. Gulledge
Dartmouth Scholarship
Serotonin (5-HT) selectively excites subpopulations of pyramidal neurons in the neocortex via activation of 5-HT2A (2A) receptors coupled to Gq subtype G-protein alpha subunits. Gq-mediated excitatory responses have been attributed primarily to suppression of potassium conductances, including those mediated by KV7 potassium channels (i.e., the M-current), or activation of non-specific cation conductances that underlie calcium-dependent afterdepolarizations (ADPs). However, 2A-dependent excitation of cortical neurons has not been extensively studied, and no consensus exists regarding the underlying ionic effector(s) involved. In layer 5 of the mouse medial prefrontal cortex, we tested potential mechanisms of serotonergic excitation …
Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova
Complement 3a Receptor In Dorsal Horn Microglia Mediates Pronociceptive Neuropeptide Signaling, Suzanne Doolen, Jennifer Cook, Maureen Riedl, Kelley Kitto, Shinichi Kohsaka, Christopher N. Honda, Carolyn A. Fairbanks, Bradley K. Taylor, Lucy Vulchanova
Physiology Faculty Publications
The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP‐21. We previously demonstrated that TLQP‐21 elicits hyperalgesia and contributes to nerve injury‐induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP‐21. We propose a novel neuroimmune signaling pathway involving TLQP‐21‐induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual‐ligand activation of C3aR1 by a neuropeptide (TLQP‐21) and an immune mediator (C3a) represents a …
Novel Calcium-Related Targets Of Insulin In Hippocampal Neurons, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Adam O. Ghoweri, Lawrence D. Brewer, Nada M. Porter, Olivier Thibault
Novel Calcium-Related Targets Of Insulin In Hippocampal Neurons, Shaniya Maimaiti, Hilaree N. Frazier, Katie L. Anderson, Adam O. Ghoweri, Lawrence D. Brewer, Nada M. Porter, Olivier Thibault
Pharmacology and Nutritional Sciences Faculty Publications
Both insulin signaling disruption and Ca2+ dysregulation are closely related to memory loss during aging and increase the vulnerability to Alzheimer's disease (AD). In hippocampal neurons, aging-related changes in calcium regulatory pathways have been shown to lead to higher intracellular calcium levels and an increase in the Ca2+-dependent afterhyperpolarization (AHP), which is associated with cognitive decline. Recent studies suggest that insulin reduces the Ca2+-dependent AHP. Given the sensitivity of neurons to insulin and evidence that brain insulin signaling is reduced with age, insulin-mediated alterations in calcium homeostasis may underlie the beneficial actions of insulin in …
Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho
Carisbamate Blockade Of T-Type Voltage-Gated Calcium Channels, Do Young Kim, Fang-Xiong Zhang, Stan T. Nakanishi, Timothy Mettler, Ik-Hyun Cho, Younghee Ahn, Florian Hiess, Lina Chen, Patrick G. Sullivan, S. R. Wayne Chen, Gerald W. Zamponi, Jong M. Rho
Spinal Cord and Brain Injury Research Center Faculty Publications
Objectives
Carisbamate (CRS) is a novel monocarbamate compound that possesses antiseizure and neuroprotective properties. However, the mechanisms underlying these actions remain unclear. Here, we tested both direct and indirect effects of CRS on several cellular systems that regulate intracellular calcium concentration [Ca2+]i.
Methods
We used a combination of cellular electrophysiologic techniques, as well as cell viability, Store Overload‐Induced Calcium Release (SOICR), and mitochondrial functional assays to determine whether CRS might affect [Ca2+]i levels through actions on the endoplasmic reticulum (ER), mitochondria, and/or T‐type voltage‐gated Ca2+ channels.
Results
In CA3 pyramidal neurons, kainic …
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
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 …
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 …
Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris
Blockade Of Astrocytic Calcineurin/Nfat Signaling Helps To Normalize Hippocampal Synaptic Function And Plasticity In A Rat Model Of Traumatic Brain Injury, Jennifer L. Furman, Pradoldej Sompol, Susan D. Kraner, Melanie M. Pleiss, Esther J. Putman, Jacob Dunkerson, Hafiz Mohmmad Abdul, Kelly N. Roberts, Stephen William Scheff, Christopher M. Norris
Pharmacology and Nutritional Sciences Faculty Publications
Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate …
Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo
Role Of The Calcium Plateau In The Neuronal Injury And Behavioral Morbidities Following Organophosphate Intoxication, Laxmikant S. Deshpande, Robert E. Blair, Kristin F. Phillips, Robert J. Delorenzo
Neurology Publications
Organophosphate (OP) chemicals include nerve agents and pesticides, and there is a growing concern of OP based chemical attacks against civilians. Current antidotes are essential in limiting immediate mortality associated with OP exposure. However, further research is needed to identify molecular mechanisms underlying long-term neurological deficits following survival of OP toxicity in order to develop effective therapeutics. We have developed rat survival models of OP induced status epilepticus (SE) that mimic chronic mortality and morbidity following OP intoxication. We have observed significant elevations in hippocampal calcium levels after OP SE that persisted for weeks following initial survival. Drugs inhibiting intracellular …
Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo
Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo
Neurology Publications
Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …
Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey
Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey
Doctoral Dissertations
Proper detection is the key to studying any processes on the cellular scale. Nowhere is this more evident than in the tight space which confines the synaptic cleft. Being able to ascertain the location of receptors on live neurons is fundamental to our understanding of not only how these receptors interact and move inside the cell but also how neurons function. Most detection methods rely on significantly altering the receptor; both tagging with a fluorescent protein or targeting the receptor by a fluorescent reporter in the form of a small molecule causes significant difficulties. These localization techniques often result in …
Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar
Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar
Graduate School of Biomedical Sciences Theses and Dissertations
Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …
The Postsynaptic Regulation Of Synaptic Strength In Drosophila, Daniel Michael Gertner
The Postsynaptic Regulation Of Synaptic Strength In Drosophila, Daniel Michael Gertner
Legacy Theses & Dissertations (2009 - 2024)
Postsynaptic Ca2+ plays an important role in synaptic homeostasis and synaptic plasticity. Postsynaptic Ca2+ signals have been shown to regulate synaptic transmission at the Drosophila larval neuromuscular junction (NMJ), however, these signals have not been well characterized. This will explore how these signals regulate synaptic strength and what channels are involved. In previous lab experiments Ca2+ transients were observed during evoked and spontaneous release (Desai and Lnenicka, 2011). It was further demonstrated that a reduction in synaptic strength occurs following synaptic stimulation. It was hypothesized that the increase in postsynaptic Ca2+ following synaptic stimulation activates the gCS and causes a …
Role Of Neurogranin In The Regulation Of Calcium Binding To Calmodulin, Anuja Chandrasekar
Role Of Neurogranin In The Regulation Of Calcium Binding To Calmodulin, Anuja Chandrasekar
Dissertations & 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, …
The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh
The Effects Of Chronic Calcium Dysregulation On Behavioral And Pathological Features Of Alzheimer's Disease, Jonathan Sabbagh
UNLV Theses, Dissertations, Professional Papers, and Capstones
Alzheimer's disease (AD) is a progressive neurodegenerative disorder whose etiology is unknown. Recent studies have implicated alterations in calcium homeostasis as a pathogenic contributor to AD. Calcium dysregulation has been observed in aged and AD brains, an event which could potentially facilitate the development of multiple pathologies observed in AD. Specifically, disrupting intracellular calcium levels in vitro has been demonstrated to increase amyloid-beta (Aβ) production, tau phosphorylation, and neuronal loss. However, there is a paucity of data on the behavioral and biochemical consequences of chronic in vivo perturbation of calcium homeostasis. In a series of experiments designed to evaluate the …
Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout
Role Of Trp Channels In Mediating The Calcium Signaling Response Of Brain Endothelial Cells To Mechanical Stretch, Jonathan Berrout
Dissertations & Theses (Open Access)
Traumatic brain injury (TBI) often results in disruption of the blood brain barrier (BBB), which is an integral component to maintaining the central nervous system homeostasis. Recently cytosolic calcium levels ([Ca2+]i), observed to elevate following TBI, have been shown to influence endothelial barrier integrity. However, the mechanism by which TBI-induced calcium signaling alters the endothelial barrier remains unknown. In the present study, an in vitro BBB model was utilized to address this issue. Exposure of cells to biaxial mechanical stretch, in the range expected for TBI, resulted in a rapid cytosolic calcium increase. Modulation of intracellular and extracellular …
Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler
Increased Mitochondrial Calcium Sensitivity And Abnormal Expression Of Innate Immunity Genes Precede Dopaminergic Defects In Pink1-Deficient Mice, Ravi S. Akundi, Zhenyu Huang, Joshua Eason, Jignesh D. Pandya, Lianteng Zhi, Wayne A. Cass, Patrick G. Sullivan, Hansruedi Büeler
Neuroscience Faculty Publications
BACKGROUND: PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice.
METHODS AND FINDINGS: Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. …
Calcium Regulation And Transmitter Release At Drosophila Larval Neuromuscular Junction, Tao He
Calcium Regulation And Transmitter Release At Drosophila Larval Neuromuscular Junction, Tao He
Legacy Theses & Dissertations (2009 - 2024)
Calcium ions act as the most versatile 2nd messenger and are involved in an incredibly broad spectrum of biological processes. Proper cellular Ca2+ homeostasis is paramount in maintaining normal cell growth, functions, survival and programmed death. Hence, understanding Ca2+ regulation has been a goal of and a hot topic in cutting-edge biological research for decades. Recently, the advent of a new generation of Ca2+ indicators has made a major contribution to advances in understanding Ca2+ regulation (Grynkiewicz et al., 1985). Likewise, the application of Drosophila melanogaster as an animal model has provided tantalizing clues and fueled the progress of research …
Forced-Exercise Alleviates Neuropathic Pain In Experimental Diabetes: Effects On Voltage-Gated Calcium Channels, Sahadev A. Shankarappa
Forced-Exercise Alleviates Neuropathic Pain In Experimental Diabetes: Effects On Voltage-Gated Calcium Channels, Sahadev A. Shankarappa
Dissertations
Exercise is now established as an integral adjunct to the management of diabetes. Diabetic polyneuropathy, a painful complication of diabetes, remains untreatable, emphasizing a critical need for improved therapeutic strategies. Recent evidence suggests that exercise may facilitate recovery of peripheral nerve function in diabetes. However, the mechanism by which exercise protects against diabetes-induced nerve dysfunction is unknown. In this dissertation we hypothesized that forced-exercise protects against experimental DPN by preventing glucose-associated alterations of voltage-gated calcium currents (VGCC) in small diameter dorsal root ganglion (DRG) neurons. Using behavioral, nerve-electrophysiology and patch-clamp methodology we examined the functional consequences of forced-exercise (treadmill, 5.4 …
Regulation Of Transglutaminase By 5-Ht2a Receptor Signaling And Calmodulin, Ying Dai
Regulation Of Transglutaminase By 5-Ht2a Receptor Signaling And Calmodulin, Ying Dai
Dissertations
Transglutaminase (TGase), nature’s biological glue, catalyzes the post-translational modification of proteins by formation of intra- and intermolecular protein cross-links or by primary amine incorporation. TGase has various physiological functions, such as skin-barrier formation and blood clot stabilization, whereas increasing evidence indicates they may also involved in neurodegenerative diseases including Huntington’s disease (HD), Alzheimer disease’s, and progressive supranuclear palsy. Mutant huntingtin (htt) and small G proteins (e.g. Rac 1) are potential substrates of TGases. The purpose of this dissertation was to characterize the mechanisms by which 5-HT2A receptor signaling and calmodulin (CaM) regulate TGase-catalyzed transamidation of Rac1 and htt in cultured …
The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis
The Endocytic Protein Numb Regulates App Metabolism And Notch Signaling: Implications For Alzheimer's Disease, George Kyriazis
Electronic Theses and Dissertations
Increased production of amyloid beta (A-beta) peptide, via altered proteolytic cleavage of amyloid protein precursor (APP), and abnormalities in neuronal calcium homeostasis play central roles in the pathogenesis of Alzheimer's disease (AD). Notch1, a membrane receptor that controls cell fate decisions during development of the nervous system, has been linked to AD because it is a substrate for the gamma-secretase protein complex in which mutations cause early-onset inherited AD. Numb is an evolutionarily conserved endocytic adapter involved in the internalization of transmembrane receptors. Mammals produce four Numb isoforms that differ in two functional domains, a phosphotyrosine-binding domain (PTB) and a …
Regulation Of Calcium Entry Pathway In Jurkat T Cells, Petronilla A. Fruasaha
Regulation Of Calcium Entry Pathway In Jurkat T Cells, Petronilla A. Fruasaha
Browse all Theses and Dissertations
Calcium release-activated calcium channels (CRAC) control influx of calcium in human T lymphocytes. Hour-long calcium elevations are necessary for efficient gene expression during T cell activation and proliferation. We report here that, the time course for store-operated Ca2+ entry is short-lived (3-4 min) and therefore, cannot account for the prolonged Ca2+ elevations necessary for NFAT translocation into nucleus. Previous findings strongly suggest that T cell activation is accompanied by cytosolic alkalinization. Here, we show that pH changes in Jurkat T cells following activation with mitogenic lectin, phytohemagglutinin (PHA), depends on the length of time of exposure and the concentration (potency) …
Role Of Calcium And Nitric Oxide Synthase (Nos) In Brain Mitochondrial Dysfunction, Vidya Nag Nukala
Role Of Calcium And Nitric Oxide Synthase (Nos) In Brain Mitochondrial Dysfunction, Vidya Nag Nukala
Theses and Dissertations--Neuroscience
Mitochondria are essential for promoting cell survival and growth through aerobic metabolism and energy production. Mitochondrial function is typically analyzed using mitochondria freshly isolated from tissues and cells because they yield tightly coupled mitochondria, whereas those from frozen tissue can consist of broken mitochondria and membrane fragments. A method, utilizing a well-characterized cryoprotectant such as dimethyl sulfoxide (DMSO), is described. Such mitochondria show preserved structure and function that presents us with a possible strategy to considerably expand the time-frame and the range of biochemical, molecular and metabolic studies that can be performed without the constraints of mitochondrial longevity ex vivo …