A5031975031- Nicotinic Acetylcholine Receptors Study
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Immune Response and Inflammation
- Vagus Nerve Stimulation Research
- Asthma and respiratory diseases
- Immune Cell Function and Interaction
- Neuropeptides and Animal Physiology
- T-cell and B-cell Immunology
- Autoimmune Neurological Disorders and Treatments
- Dermatology and Skin Diseases
- Immunotherapy and Immune Responses
- Biochemical Analysis and Sensing Techniques
- Chemical Synthesis and Analysis
- Olfactory and Sensory Function Studies
- Photoreceptor and optogenetics research
- Antimicrobial Peptides and Activities
- Tryptophan and brain disorders
- Smoking Behavior and Cessation
- Lipid Membrane Structure and Behavior
- Amino Acid Enzymes and Metabolism
- IL-33, ST2, and ILC Pathways
- Cancer Research and Treatments
Geriatric Research Education and Clinical Center
2005-2024
Lake City VA Medical Center
1996-2024
University of Utah
2008-2020
VA Salt Lake City Healthcare System
2004-2015
United States Department of Veterans Affairs
2003
General Department of Preventive Medicine
1999
Huntsman Cancer Institute
1997
Scripps Research Institute
1993
Scripps Health
1989-1991
Scripps Clinic
1989-1991
Rasmussen's encephalitis is a progressive childhood disease of unknown cause characterized by severe epilepsy, hemiplegia, dementia, and inflammation the brain. During efforts to raise antibodies recombinant glutamate receptors (GluRs), behaviors typical seizures histopathologic features mimicking were found in two rabbits immunized with GluR3 protein. A correlation was between presence serum detected protein immunoblot analysis immunoreactivity transfected cells expressing GluR3. Repeated...
Abstract The proinflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α are produced within the CNS, and, similar to periphery, they have pleotrophic overlapping functions. We shown previously that increases neuronal survival a toxic influx of calcium mediated through N-methyl-d-aspartic acid (NMDA) glutamate-gated ion channels. This process, termed excitotoxicity, is major contributor death following ischemia or stroke. Neuroprotection by this cytokine requires both activation p55/TNF receptor...
People who begin daily smoking at an early age are greater risk of long-term nicotine addiction. We tested the hypothesis that associations between nicotinic acetylcholine receptor (nAChR) genetic variants and dependence assessed in adulthood will be stronger among smokers began exposure during adolescence. compared addiction-measured by Fagerstrom Test Nicotine Dependence-in three cohorts recruited Utah, Wisconsin, NHLBI Lung Health Study, using a candidate-gene approach with neuronal nAChR...
Keratinocytes produce a molecule, epidermal-derived thymocyte activating factor (ETAF), which is biologically and physiochemically similar to the polypeptide hormone interleukin 1 (IL-1). Because stratum corneum (SC) composed of terminally differentiated keratinocytes, we questioned whether ETAF/IL-1 could be isolated from this tissue. The extraction normal human SC with physiologic saline solution yielded large amount activity, as measured by in vitro co-stimulator assay. SC-derived...
UV radiation was found to enhance the release by keratinocytes of epidermal cell thymocyte-activating factor (ETAF), a hormone-like molecule that is physiochemically identical interleukin 1 (IL-1). This conclusion supported following observations: (i) keratinocyte line PAM 212 retained ETAF/IL-1-producing potential after exposure despite significant loss in viability; (ii) cells from normal and radiation-exposed mice were produce equivalent amounts ETAF/IL-1 on per basis with density skin...
Abstract Autoimmune processes are initiated when tolerance to self-proteins fails be established or maintained and immune cells stimulated by self-Ags. Although intracellular autoantigens common, the origin of extracellular is poorly defined possibly more dangerous. In this study, we considered a mechanism for an autoantigen from neuronal glutamate receptor subunit 3 (GluR3) in Rasmussen’s encephalitis, severe form pediatric epilepsy. We demonstrate that specific cleavage GluR3 granzyme B...
A total of 81 avirulent Tn10 insertion mutants Salmonella typhimurium have previously been described. These were selected for the inability to survive in murine macrophages. We characterized abilities most these adhere to, invade, and replicate both macrophages nonphagocytic epithelial cells. The results suggest that contain a defect is specific survival within professional phagocytes. invaded replicated normally human colon adenocarcinoma cells (Caco-2) but did not macrophage cell line...
Excitotoxic neuronal death mediated by N-methyl-D-aspartate (NMDA) glutamate receptors can contribute to the extended brain damage that often accompanies trauma or disease. Both inflammatory cytokine tumor necrosis factor-α (TNF-α) and nicotine have been identified as possible neuroprotective agents NMDA assault. We find TNF-α protection of a subpopulation cultured cortical neurons chronic NMDA-mediated excitotoxic requires both activation p55/TNFRI, but not p75/TNFRII, release endogenous...
We have examined the expression of inflammatory cytokine, tumor necrosis factor alpha (TNFα) in mouse brain. Using immunohistochemical methods developed, we found anti-TNFα immunoreactivity localized basal ganglia and other discrete brain structures. Constitutive immunoreactivity, present normal, unstimulated brain, was observed glial microglial-like cells, but it predominant neuronal-like cells. Intravenous administration lipopolysaccharide (LPS) increased TNFα transcript levels detected by...
Oligodendrocyte precursor cells (O2A/OPC, A2B5(+)) were examined for expression of neuronal nicotinic acetylcholine receptors (nAChR). RT-PCR analysis and immunocytochemistry O2A/OPCs purified from the rat corpus collusum revealed nAChR subunits alpha3, alpha4, alpha5, alpha7, beta2, beta4. Immunoreactivity toward was not detected in induced to differentiate into either oligodendrocytes or astrocytes. Approximately 65% loaded with calcium-responsive dye FURA-2 increased their intracellular...
Abstract Neuronal nicotinic acetylcholine receptor (nAChR) expression and function are customized in different brain regions through assembling receptors from closely related but genetically distinct subunits. Immunohistochemical analysis of one these subunits, nAChRβ4, the mouse suggests an extensive potentially diverse role for this subunit both excitatory inhibitory neurotransmission. Prominent immunostaining included: 1) medial habenula, efferents composing fasciculus retroflexus,...
The distribution of the neuronal nicotinic acetylcholine receptor subunit α4 (nAChRα4) in brains young (2–4 months) or aged (24–28 CBA/J mice was examined using immunohistochemical staining. Anti-nAChRα4 immunoreactivity corresponded with nAChRα4 RNA expression and high-affinity [ 3 H]nicotine binding. Immunostaining relative to that animals diminished medial septum diagonal band but unchanged globus pallidus substantia nigra. staining neurons almost completely absent hippocampus animals....
Abstract The response by individuals to nicotine is likely reflect the interaction of this compound with target nAChRs. However, resolving how different genetic backgrounds contribute unique mouse strain‐specific responses remains an important and unresolved issue. To examine question in detail, expression acetylcholine receptor (nAChR) subunits α3, α4, α5, α7, β2, β4 was measured dorsal hippocampus using immunohistochemistry strains or lines BALB/c, C3H/J, C57BL/6, CBA/J, DBA/2, Long Sleep...
Nicotine modulates multiple inflammatory responses in the lung through nicotinic acetylcholine receptor subtype alpha7 (α7). Previously we reported that α7 both hematopoietic and epithelium to bacterial inflammogen, lipopolysaccharide (LPS). Here apply immunohistochemistry, flow cytometry RNA-Seq analysis of isolated distal further define α7-expression function this tissue. Mouse lines were used co-express a bicistronic tau-green fluorescent protein (tGFP) as reporter (α7G) expression harbor...
Abstract Nicotine, the causative agent of addiction to tobacco, can also be a neuroprotectant. Nicotine‐induced neuroprotection against different toxins is imparted through pharmacologically distinct neuronal nicotinic acetylcholine receptors (nAChR) where protection chronic N ‐methyl‐ d ‐aspartic acid (NMDA) exposure nAChRα7 but toxic peptide amyloid precursor protein, Aβ 25−35 , nAChRα4β2. The inflammatory cytokine tumor necrosis factor alpha (TNFα) neuroprotective, however, in presence...
How inflammatory responses are mechanistically modulated by nicotinic acetylcholine receptors (nAChR), especially composed of alpha7 (α7) subunits, is poorly defined. This includes a precise definition cells that express α7 and how these impact on innate responses. To this aim we used mice generated through homologous recombination an Ires-Cre-recombinase bi-cistronic extension the endogenous gene when crossed with reporter mouse expressing Rosa26-LoxP (yellow fluorescent protein (YFP))...
Ionotropic glutamate receptor (GluR) expression and function is regulated through multiple pre- post-translational mechanisms. We find that limited proteolytic cleavage of GluR3 at two distinct sites generates stable short forms are glycosylated found in association with other full-length GluRs the mouse brain cultured primary neurons. A combination mutagenesis transfection into HEK293 cells revealed by a γ-secretase-like activity within membrane-localized re-entry loop or near...
The IfitmDel mouse lacks all five of the Ifitm genes via LoxP deletion. This animal breeds normally with no obvious defect in development. animals exhibit a steady and significantly enhanced weight gain relative to wild-type controls beginning about three months age under normal feeding conditions. increased corresponds elevated fat mass, tolerance tests they are hyporesponsive insulin but respond glucose. Both young (4 mo) older (12 mice have levels serum leptin suggesting leptin/leptin...
We reported (Twyman, R. E., Gahring, L. C., Speiss, J., and Rogers, S. W. (1995) Neuron 14, 755-762) that antibodies to a subregion of the glutamate receptor (GluR) subunit GluR3 termed GluR3B (amino acids 372-395), act as highly specific GluR agonists. In this study we produced additional rabbit anti-GluR3B-specific antibodies, ranked them according their ability function agonists characterized immunoreactivity using deletion alanine substitution mutagenesis. These anti-GluR3B bound subset...