A5010299816- Gastrointestinal motility and disorders
- Pain Mechanisms and Treatments
- Diet and metabolism studies
- Gut microbiota and health
- Ion Channels and Receptors
- Biochemical effects in animals
- Dietary Effects on Health
- Pain Management and Placebo Effect
- Autophagy in Disease and Therapy
- Cannabis and Cannabinoid Research
- Neuroscience and Neuropharmacology Research
- Helicobacter pylori-related gastroenterology studies
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Botulinum Toxin and Related Neurological Disorders
- Vagus Nerve Stimulation Research
- Barrier Structure and Function Studies
- Stress Responses and Cortisol
- Ion channel regulation and function
- Color perception and design
- Enhanced Recovery After Surgery
- Genetics, Aging, and Longevity in Model Organisms
- Electrolyte and hormonal disorders
- Exercise and Physiological Responses
- Congenital gastrointestinal and neural anomalies
- Neurological and metabolic disorders
University of Michigan–Ann Arbor
2006-2022
Novem (Netherlands)
2008
GTx (United States)
2008
Michigan Medicine
2008
In-Q-Tel
2008
Ann Arbor Center for Independent Living
2006
University of Illinois Urbana-Champaign
2000
Diabetes mellitus is associated with one or more kinds of stimulus-evoked pain including hyperalgesia and allodynia. The mechanisms underlying painful diabetic neuropathy remain poorly understood. Previous studies demonstrate an important role vanilloid receptor 1 (VR1) in inflammation injury-induced pain. Here we investigated the function expression VR1 dorsal root ganglion (DRG) neurons isolated from streptozotocin-induced rats between 4 8 weeks after onset diabetes. DRG showed significant...
Voltage-gated sodium channel (Na v 1) β2 subunits modulate gating, assembly, and cell-surface expression in CNS neurons vitro vivo . increases sensory after nerve injury, development of mechanical allodynia the spared injury model is attenuated β2-null mice. Thus, we hypothesized that modulates electrical excitability dorsal root ganglion (DRG) We compared currents ( I Na ) small DRG from +/+ −/− mice to determine effects on tetrodotoxin-sensitive (TTX-S) tetrodotoxin-resistant (TTX-R) 1...
Chronic stress and elevated glucocorticoid hormone are associated with decreases in the intestinal epithelial tight junction protein claudin-1 (CLDN1). Human/rat CLDN1 promoters contain response elements (GREs) adjacent transcription repressor HES1 binding N-boxes. Notch signaling target expression was high receptor (NR3C1) low at crypt base pattern reversed apex. reduced overall rat colon NR3C1 that downregulation. Chromatin-immunoprecipitation experiments showed bind to promoter crypts....
Abstract Background Chronic psychological stress is associated with increased intestinal epithelial permeability and visceral hyperalgesia. Lubiprostone, an agonist for chloride channel‐2, promotes secretion accelerates restoration of injury‐induced barrier dysfunction. The mechanisms underlying how lubiprostone regulates colon function hyperalgesia in chronic remain unknown. Methods Male rats were subjected to water avoidance 10 consecutive days. Lubiprostone was administered daily during...
We examined the hypothesis that activation of apoptosis cascade occurs relatively early in diabetes mellitus affecting three distinct neuronal populations are involved regulating gut function: (i) dorsal root ganglion (DRG), (ii) vagus nodose and (iii) colon myenteric plexus. A validated streptozotocin-induced diabetic rat model age-matched healthy controls were studied. After 4-8 weeks animals anaesthetized, fixed situ relevant tissues removed. 1 month some treated with insulin for 2 to...
The etiology of diabetic neuropathy is multifactorial and not fully elucidated, although oxidative stress mitochondrial dysfunction are major factors. We reported previously that complement-inactivated sera from type 2 patients with induce apoptosis in cultured neuronal cells, possibly through an autoimmune immunoglobulin-mediated pathway. Recent evidence supports emerging role for autophagy a variety diseases. Here we report exposure human neuroblastoma SH-SY5Y cells to associated increased...
Abstract Chronic diabetic neuropathy is associated with peripheral demyelination and degeneration of nerve fibers. The mechanism(s) underlying neuronal injury in sensory remain poorly understood. Recently, we reported increased expression function transient receptor potential vanilloid 1 (TRPV1) large dorsal root ganglion (DRG) neurons neuropathy. In this study, examined the effects TRPV1 activation on cell pathways subpopulation streptozotocin‐induced rat model. Large DRG from (6–8 weeks)...
Chronic stress is associated with activation of the HPA axis, elevation in pro-inflammatory cytokines, decrease intestinal epithelial cell tight junction (TJ) proteins, and enhanced visceral pain. It unknown whether epigenetic regulatory pathways play a role chronic stress-induced barrier dysfunction hyperalgesia.Young adult male rats were subjected to water avoidance ± H3K9 methylation inhibitors or siRNAs. Visceral pain response was assessed. Differentiated Caco-2/BBE cells human colonoids...
A clearer understanding of the mechanisms underlying development and progression diabetic neuropathy is likely to indicate new directions for treatment this complication diabetes. In present study we investigated expression cannabinoid CB<sub>1</sub> receptors in models neuropathy. PC12 cells were differentiated into a neuronal phenotype with nerve growth factor (NGF) (50 ng/ml) varying concentrations glucose (5.5–50 mM). receptor was studied at mRNA level by reverse transcriptase-polymerase...
Stress is known to perturb the microbiome and exacerbate irritable bowel syndrome (IBS) associated symptoms. Characterizing structural functional changes in necessary understand how alterations affect biomolecular environment of gut IBS. Repeated water avoidance (WA) stress was used induce IBS-like symptoms rats. The colon-mucosa characterized 13 stressed control animals by 16S sequencing. In silico analysis domains microbial communities done inferring metagenomic profiles from data....
Abstract In humans, chronic psychological stress is associated with increased intestinal paracellular permeability and visceral hyperalgesia, which recapitulated in the intermittent water avoidance (WAS) rat model. However, it unknown whether enhanced pain are intrinsically linked correlate. Treatment of rats lubiprostone during WAS significantly reduced WAS-induced changes epithelial hyperalgesia a subpopulation rats. Lubiprostone also prevented decreases tight junction protein, occludin...
Chronic stress is commonly associated with enhanced abdominal pain (visceral hypersensitivity), but the cellular mechanisms underlying how chronic induces visceral hypersensitivity are poorly understood. In this study, we examined changes in gene expression colon epithelial cells from a rat model using RNA-sequencing to examine stress-induced transcriptome. Following stress, most significantly up-regulated genes included Atg16l1, Coq10b, Dcaf13, Nat2, Ptbp2, Rras2, Spink4 and down-regulated...
We reported previously that sera from patients with type 2 diabetes and neuropathy induce autophagy in human neuroblastoma (SH-SY5Y) cells. Here we report enriched immunoglobulin fractions a subpopulation of these colocalization Fas-activated death domain (FADD), component the receptor signaling pathway. These effects were replicated by treatment SY5Y cells Fas ligand, tumor necrosis factor alpha an agonist anti-Fas antibody. Preincubation soluble chimera (extracellular domain) markedly...