Protein Kinase A And Epac Mediate Chronic Pain After Injury: Prolonged Inhibition By Endogenous Y1 Receptors In Dorsal Horn,
2016
University of Kentucky
Protein Kinase A And Epac Mediate Chronic Pain After Injury: Prolonged Inhibition By Endogenous Y1 Receptors In Dorsal Horn, Weisi Fu
Theses and Dissertations--Physiology
Inflammation or nerve injury sensitizes several populations of nociceptive neurons in the dorsal horn of the spinal cord, including those that express the neuropeptide Y (NPY) Y1 receptor (Y1R). Our overall hypothesis is that after tissue or nerve injury, these Y1R-expressing neurons enter a state of latent sensitization (LS) that contributes to vulnerability to the development of chronic pain; furthermore, LS is under the tonic inhibitory control of endogenous Y1R signaling. First, we evaluated the intracellular signaling pathways that become activated in Y1R-expressing neurons and participate in LS. To do this, we established behavioral models of inflammatory or neuropathic pain, …
Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes,
2016
University of Kentucky
Regulation Of Uv-Protective Pathways Downstream Of The Melanocortin 1 Receptor In Melanocytes, Erin M. Wolf Horrell
Theses and Dissertations--Physiology
Malignant cutaneous melanoma is the deadliest form of skin cancer, and a majority of melanoma diagnoses are a result of exposure to ultraviolet (UV) radiation. UV radiation causes DNA damage, which if not repaired correctly via nucleotide excision repair (NER) can result in mutations and melanomagenesis. The melanocortin 1 receptor (MC1R) is a Gs protein coupled receptor located on melanocyte plasma membranes and is involved in protecting the skin from UV induced damage. MC1R signaling results in the activation of two protective pathways: 1) induction of eumelanin synthesis downstream of micropthalmia-associated transcription factor (MITF) and 2) acceleration of NER …
Histological And Behavioral Consequences Of Repeated Mild Traumatic Brain Injury In Mice,
2016
University of Kentucky
Histological And Behavioral Consequences Of Repeated Mild Traumatic Brain Injury In Mice, Amanda Nicholle Bolton Hall
Theses and Dissertations--Physiology
The majority of the estimated three million traumatic brain injuries that occur each year are classified as “mild” and do not require surgical intervention. However, debilitating symptoms such as difficulties focusing on tasks, anxiety, depression, and visual deficits can persist chronically after a mild traumatic brain injury (TBI) even if an individual appears “fine”. These symptoms have been observed to worsen or be prolonged when an individual has suffered multiple mild TBIs. To test the hypothesis that increasing the amount of time between head injuries can reduce the histopathological and behavioral consequences of repeated mild TBI, a mouse model of …
Determining The Effect Of Knocking Out Microrna-21 On Subsarcolemmal And Interfibrillar Mitochondria,
2016
Virginia Commonwealth University
Determining The Effect Of Knocking Out Microrna-21 On Subsarcolemmal And Interfibrillar Mitochondria, Madhur Batra
Theses and Dissertations
Type 2 diabetes mellitus is a growing problem across the world and has significant pathological changes associated with it, including diabetic cardiomyopathy, wherein cardiac function is reduced. MicroRNA-21 has been shown to play a role in both the heart and diabetes so it was thought that knocking out miR-21 could have a protective effect on oxidative phosphorylation function in diabetic mice. Subsarcolemmal and interfibrillar mitochondria were isolated from adult male WT, miR-21 KO, db/db, and double knockout mice (db/db and miR-21 KO cross) and evaluated for function. Knocking out miR-21 in diabetic mice showed a restorative effect in Complex I …
Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity,
2016
University of Nebraska Medical Center
Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity, Adam J. Case, Daniel Agraz, Iman M. Ahmad, Matthew C. Zimmerman
Journal Articles: Cellular & Integrative Physiology
No abstract provided.
Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis.,
2016
University of Minnesota
Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman
Journal Articles: Cellular & Integrative Physiology
Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (∙-)) in the OVLT contribute to the hypertensive effects …
Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis.,
2016
University of Minnesota
Angiotensin Ii-Induced Hypertension Is Attenuated By Overexpressing Copper/Zinc Superoxide Dismutase In The Brain Organum Vasculosum Of The Lamina Terminalis., John P. Collister, Heather Taylor-Smith, Donna Drebes, David Nahey, Jun Tian, Matthew C. Zimmerman
Journal Articles: Cellular & Integrative Physiology
Angiotensin II (AngII) can access the brain via circumventricular organs (CVOs), including the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), to modulate blood pressure. Previous studies have demonstrated a role for both the SFO and OVLT in the hypertensive response to chronic AngII, yet it is unclear which intracellular signaling pathways are involved in this response. Overexpression of copper/zinc superoxide dismutase (CuZnSOD) in the SFO has been shown to attenuate the chronic hypertensive effects of AngII. Presently, we tested the hypothesis that elevated levels of superoxide (O2 (∙-)) in the OVLT contribute to the hypertensive effects …
Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity.,
2016
University of Nebraska Medical Center
Low-Dose Aronia Melanocarpa Concentrate Attenuates Paraquat-Induced Neurotoxicity., Adam J. Case, D Agraz, Iman M. Ahmad, Matthew C. Zimmerman
Journal Articles: Cellular & Integrative Physiology
Herbicides containing paraquat may contribute to the pathogenesis of neurodegenerative disorders such as Parkinson's disease. Paraquat induces reactive oxygen species-mediated apoptosis in neurons, which is a primary mechanism behind its toxicity. We sought to test the effectiveness of a commercially available polyphenol-rich Aronia melanocarpa (aronia berry) concentrate in the amelioration of paraquat-induced neurotoxicity. Considering the abundance of antioxidants in aronia berries, we hypothesized that aronia berry concentrate attenuates the paraquat-induced increase in reactive oxygen species and protects against paraquat-mediated neuronal cell death. Using a neuronal cell culture model, we observed that low doses of aronia berry concentrate protected against paraquat-mediated …
Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity,
2015
University of Nebraska Medical Center
Interaction Between Angiotensin Ii And Bdnf In Modulating Sympathetic Nerve Activity, Bryan K. Becker
Theses & Dissertations
Over activation of the sympathetic nervous system is prevalent in many forms of cardiovascular disease such as chronic heart failure (CHF) and hypertension. Although increased neuronal renin-angiotensin system activity in presympathetic neurons has been well implicated in mediating this sympatho-excitation, many of the neuronal effects of angiotensin II (Ang II) signaling remain poorly understood. One particular mechanism of Ang II-mediated increases in presympathetic neuronal activity is through reductions in voltage-gated K+ currents. Another pathway that has profound effects on neuronal K+ currents and that has been previously implicated in Ang II-signaling is brain-derived neurotrophic factor (BDNF) activity through …
Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase,
2015
LSU Health Sciences Center - New Orleans
Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi
School of Medicine Faculty Publications
The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …
Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells.,
2015
University of Nebraska Medical Center
Bdnf Contributes To Angiotensin Ii-Mediated Reductions In Peak Voltage-Gated K+ Current In Cultured Cath.A Cells., Bryan K. Becker, Han-Jun Wang, Changhai Tian, Irving H. Zucker
Journal Articles: Cellular & Integrative Physiology
Increased central angiotensin II (Ang II) levels contribute to sympathoexcitation in cardiovascular disease states such as chronic heart failure and hypertension. One mechanism by which Ang II increases neuronal excitability is through a decrease in voltage-gated, rapidly inactivating K(+) current (IA); however, little is known about how Ang II signaling results in reduced IA. Brain-derived neurotrophic factor (BDNF) has also been demonstrated to decrease IA and has signaling components common to Ang II. Therefore, we hypothesized that Ang II-mediated suppression of voltage-gated K(+) currents is due, in part, to BDNF signaling. Differentiated CATH.a, catecholaminergic cell line treated with BDNF for …
Diabetic Ketoacidosis: Pathophysiology And Treatment,
2015
Liberty University
Diabetic Ketoacidosis: Pathophysiology And Treatment, Laura E. Mumme
The Kabod
The pathophysiology of DKA in patients with T1D is addressed, followed by a discussion of proper emergency treatment for this life-threatening condition.
Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure.,
2015
Universidad Autónoma de Chile
Relevance Of The Carotid Body Chemoreflex In The Progression Of Heart Failure., David C. Andrade, Claudia Lucero, Camilo Toledo, Carlos Madrid, Noah J. Marcus, Harold D. Schultz, Rodrigo Del Rio
Journal Articles: Cellular & Integrative Physiology
Chronic heart failure (CHF) is a global health problem affecting millions of people. Autonomic dysfunction and disordered breathing patterns are commonly observed in patients with CHF, and both are strongly related to poor prognosis and high mortality risk. Tonic activation of carotid body (CB) chemoreceptors contributes to sympathoexcitation and disordered breathing patterns in experimental models of CHF. Recent studies show that ablation of the CB chemoreceptors improves autonomic function and breathing control in CHF and improves survival. These exciting findings indicate that alterations in CB function are critical to the progression of CHF. Therefore, better understanding of the physiology of …
Standardization Of The Experimental Autoimmune Myasthenia Gravis (Eamg) Model By Immunization Of Rats With Torpedo Californica Acetylcholine Receptors- Recommendations For Methods And Experimental Designs.,
2015
George Washington University
Standardization Of The Experimental Autoimmune Myasthenia Gravis (Eamg) Model By Immunization Of Rats With Torpedo Californica Acetylcholine Receptors- Recommendations For Methods And Experimental Designs., Mario Losen, Pilar Martinez-Martinez, Peter C. Molenaar, Konstantinos Lazaridis, Socrates Tzartos, Talma Brenner, Rui-Sheng Duan, Jie Luo, Jon Lindstrom, Linda Kusner
Pharmacology and Physiology Faculty Publications
Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR) is characterized by a chronic, fatigable weakness of voluntary muscles. The production of autoantibodies involves the dysregulation of T cells which provide the environment for the development of autoreactive B cells. The symptoms are caused by destruction of the postsynaptic membrane and degradation of the AChR by IgG autoantibodies, predominantly of the G1 and G3 subclasses. Active immunization of animals with AChR from mammalian muscles, AChR from Torpedo or Electrophorus electric organs, and recombinant or synthetic AChR fragments generates a chronic model of MG, termed experimental autoimmune myasthenia gravis (EAMG). …
Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity In The ∆7 Sma Mouse,
2015
Wright State University - Main Campus
Plastin 3 Expression Does Not Modify Spinal Muscular Atrophy Severity In The ∆7 Sma Mouse, Vicki L. Mcgovern, Aurelie Massoni-Laporte, Xueyong Wang, Thanh T. Le, Hao T. Le, Mark M. Rich, Arthur H. M. Burghes
Neuroscience, Cell Biology & Physiology Faculty Publications
Spinal muscular atrophy is caused by loss of the SMN1 gene and retention of SMN2. TheSMN2 copy number inversely correlates with phenotypic severity and is a modifier of disease outcome. The SMN2 gene essentially differs from SMN1 by a single nucleotide in exon 7 that modulates the incorporation of exon 7 into the final SMN transcript. The majority of the SMN2transcripts lack exon 7 and this leads to a SMN protein that does not effectively oligomerize and is rapidly degraded. However theSMN2 gene does produce some full-length SMN and theSMN2 copy number along with how …
Higher Hepatic Mir-29 Expression In Undernourished Male Rats During The Postnatal Period Targets The Long-Term Repression Of Insulin-Like Growth Factor 1,
2015
Western University
Higher Hepatic Mir-29 Expression In Undernourished Male Rats During The Postnatal Period Targets The Long-Term Repression Of Insulin-Like Growth Factor 1, Gurjeev Sohi, Andrew Revesz, Julie Ramkumar, Daniel B. Hardy
Physiology and Pharmacology Publications
A nutritional mismatch in postnatal life of low birth weight offspring increases the risk of developing the metabolic syndrome. Moreover, this is associated with decreased hepatic insulin-like growth factor 1 (Igf1) expression, leading to impaired growth and metabolism. Previously we have demonstrated that the timing of nutritional restoration in perinatal life can differentially programhepatic gene expression. While micro RNAs also play an important role in silencing gene expression, to date, the impact of a nutritional mismatch in neonatal life on their long-term expression has not been evaluated. Given the complementarity of miR-29 to the 3i-UTR of Igf1, we examined how …
Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease.,
2015
Universidad Autónoma de Chile
Editorial: Carotid Body: A New Target For Rescuing Neural Control Of Cardiorespiratory Balance In Disease., Rodrigo Del Rio, Rodrigo Iturriaga, Harold D. Schultz
Journal Articles: Cellular & Integrative Physiology
No abstract provided.
Lipid Regulation As A Critical Factor In The Development Of Alzheimer's Disease,
2015
Loma Linda University
Lipid Regulation As A Critical Factor In The Development Of Alzheimer's Disease, Michael A. Castello
Loma Linda University Electronic Theses, Dissertations & Projects
Alzheimer’s disease (AD) is the most common form of dementia in the United States, representing around eighty percent of all cases. For more than two decades, researchers have been led by the amyloid cascade hypothesis, which assumes that accumulation of the amyloid peptide Aβ, derived by proteolytic processing from the amyloid precursor protein (APP), is the key pathogenic trigger in AD. To date, therapies have largely focused on removing Aβ from the brain, an approach that has produced disappointing clinical outcomes. I present an alternative hypothesis in which Aβ production and aggregation is a symptom of a larger, systemic disease …
Long-Term Hypoxia Alters Ovine Fetal Adrenal Enos And Cortisol Biosynthesis,
2015
Loma Linda University
Long-Term Hypoxia Alters Ovine Fetal Adrenal Enos And Cortisol Biosynthesis, Elizabeth Anne Newby
Loma Linda University Electronic Theses, Dissertations & Projects
Maintaining normal levels of cortisol in response to chronic stress, while retaining the ability to respond to acute stress, is important for ensuring normal fetal growth and development. Long-term hypoxia (LTH) causes adaptations in the fetal hypothalamopituitary- adrenal (HPA) axis that maintain basal cortisol levels but enhance production in response to a secondary stress. Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS) in the adrenal cortex, plays a significant role in regulating cortisol production in the LTH fetus. The production of NO is regulated by eNOS activity which can be altered via phosphorylation through key signaling pathways. In …
Identifying The Molecular Mechanisms Of Early Cachexia Using Whole Transcriptome Sequencing In Muscle And Fat Biopsies From Cancer Patients,
2015
United Arab Emirates University
Identifying The Molecular Mechanisms Of Early Cachexia Using Whole Transcriptome Sequencing In Muscle And Fat Biopsies From Cancer Patients, Amal Hussain Al Hadad
Dissertations
Cancer cachexia is responsible for one third of cancer–related deaths and contributes to the death of many others. More than 80% of cancer patients are cachectic towards the end of life. Despite intensive research, the mechanisms of cancer cachexia are still poorly understood. It is our hypothesis that identification of early changes in gene expression in cachexia will lead to an improved understanding of the mechanism that trigger this important problem in cancer patients. Thus, to shed light on the mechanisms involved in the major cachexia target tissues, we investigated the entire transcriptome in muscle and fat to identify altered …
