A5016718532- Pain Mechanisms and Treatments
- Nerve injury and regeneration
- Adipose Tissue and Metabolism
- Botulinum Toxin and Related Neurological Disorders
- Mitochondrial Function and Pathology
- Biochemical effects in animals
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Metabolism, Diabetes, and Cancer
- Receptor Mechanisms and Signaling
- Rabies epidemiology and control
- Parkinson's Disease Mechanisms and Treatments
- Sirtuins and Resveratrol in Medicine
- Calpain Protease Function and Regulation
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Axon Guidance and Neuronal Signaling
- Signaling Pathways in Disease
- Photosynthetic Processes and Mechanisms
- Neurological Disorders and Treatments
- Diet and metabolism studies
- Alzheimer's disease research and treatments
- Endoplasmic Reticulum Stress and Disease
- Skin and Cellular Biology Research
- Ion channel regulation and function
St. Boniface Hospital
2015-2025
University of Manitoba
2015-2025
University of California, San Diego
2020
University Health Network
2020
Krembil Research Institute
2020
University of Toronto
2020
Norfolk General Hospital
2018
Manitoba Beekeepers' Association
2014
Research Institute of General Pathology and Pathophysiology, the Russian Academy of Medical Sciences
2014
La Jolla Alcohol Research
2014
Significance We provide new, exciting evidence for a previously unidentified signaling pathway that mechanistically links mitochondrial respiratory chain defects to necrosis and heart failure induced by the chemotherapy agent doxorubicin (DOX). specifically show DOX disrupts protein complexes between key proteins, including uncoupling 3 cytochrome c oxidase, resulting in abnormal respiration through mechanism contingent on Bcl-2-like 19kDa-interacting (Bnip3). Perhaps most compelling is our...
The onset of diabetic neuropathy, a complication diabetes mellitus, has been linked to poor glycemic control. We tested the hypothesis that mitogen-activated protein kinases (MAPK) form transducers for damaging effects high glucose. In cultures adult rat sensory neurons, glucose activated JNK and p38 MAPK but did not result in cell damage. However, oxidative stress ERK MAPKs resulted cellular dorsal root ganglia streptozotocin-induced rats (a model type I diabetes), were at 8 wk duration,...
Mitochondrial dysfunction occurs in sensory neurons and may contribute to distal axonopathy animal models of diabetic neuropathy. The adenosine monophosphate-activated protein kinase peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signalling axis senses the metabolic demands cells regulates mitochondrial function. Studies muscle, liver cardiac tissues have shown that activity PGC-1α is decreased under hyperglycaemia. In this study, we tested hypothesis deficits...
The formation of vertebrate neural circuitry is regulated in part by neurotrophic agents, such as nerve growth factor (NGF); however, the biochemical mechanisms involved neurite outgrowth have yet to be completely resolved. Phorbol ester tumor promoters are known influence extension neurites a variety neurodevelopmental systems, and protein kinase C, major phorbol receptor, has been implicated this process. In present study, sphingosine, specific pharmacological inhibitor was employed...
OBJECTIVE Reactive oxygen species (ROS) are pro-oxidant factors in distal neurodegeneration diabetes. We tested the hypothesis that sensory neurons exposed to type 1 diabetes would exhibit enhanced ROS and oxidative stress determined whether this was associated with abnormal axon outgrowth. RESEARCH DESIGN AND METHODS Lumbar dorsal root ganglia from normal or 3- 5-month streptozotocin (STZ)-diabetic rats were cultured 10 25–50 mmol/l glucose. Cell survival outgrowth assessed. analyzed using...
OBJECTIVE Impairments in mitochondrial function have been proposed to play a role the etiology of diabetic sensory neuropathy. We tested hypothesis that dysfunction axons neurons type 1 diabetes is due abnormal activity respiratory chain and an altered proteome. RESEARCH DESIGN AND METHODS Proteomic analysis using stable isotope labeling with amino acids cell culture (SILAC) determined expression proteins mitochondria from dorsal root ganglia (DRG) control, 22-week-old streptozotocin...
Impairments in mitochondrial physiology may play a role diabetic sensory neuropathy. We tested the hypothesis that dysfunction neurons is due to abnormal respiratory function.Rates of oxygen consumption were measured mitochondria from dorsal root ganglia (DRG) 12- to- 22-week streptozotocin (STZ)-induced rats, rats treated with insulin, and age-matched controls. Activities expression components complexes reactive species (ROS) analyzed.Rates coupled respiration pyruvate + malate (P M)...
Myocardial ischemia-reperfusion (I/R) injury increases the generation of oxidized phosphatidylcholines (OxPCs), which results in cell death. However, mechanism by OxPCs mediate death and cardiac dysfunction is largely unknown. The aim this study was to determine mechanisms OxPC triggers cardiomyocyte during reperfusion injury. Adult rat ventricular cardiomyocytes were treated with increasing concentrations various purified fragmented OxPCs. Cardiomyocyte viability, bioenergetic response,...
Introduction: Metformin is currently first line therapy for type 2 diabetes (T2D). The mechanism of action metformin involves activation AMP-activated protein kinase (AMPK) to enhance mitochondrial function (for example, biogenesis, refurbishment and dynamics) autophagy. Many neurodegenerative diseases the central peripheral nervous systems arise from metabolic failure toxic aggregation where activated AMPK could prove protective. Areas covered: authors review literature on treatment in...
In rodent models of diabetes, there are expression deficits in nerve growth factor (NGF) and mRNA for its high-affinity receptor, trkA, leading to decreased retrograde axonal transport NGF support NGF-dependent sensory neurons, with reduced their neuropeptides, substance P calcitonin gene-related peptide (CGRP). Treatment diabetic rats intensive insulin normalized these deficits, treatment exogenous caused dose-related increases, giving levels neuropeptides that were greater than those...
Mitochondrial dysfunction has been proposed as a mediator of neurodegeneration in diabetes complications. The aim this study was to determine whether deficits insulin-dependent neurotrophic support contributed depolarization the mitochondrial membrane sensory neurons streptozocin (STZ)-induced diabetic rats. Whole cell fluorescent video imaging using rhodamine 123 (R123) used monitor inner potential (Δψm). Treatment cultured dorsal root ganglia (DRG) from normal adult rats for up 1 day with...
Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat the streptozocin-induced rat--have been used to determine whether such a phenomenon is involved etiology symmetrical sensory polyneuropathy commonly associated with diabetes. There was two- threefold (P < 0.05) elevation lumbar dorsal root ganglia (DRG) rats that localized perikarya medium large neurons using...
Diabetic neuropathy is a major complication of diabetes that affects the sensory and autonomic nervous systems leads to significant morbidity impact on quality life patients. Mitochondrial stress has been proposed as mediator neurodegeneration in diabetes. This review briefly summarizes nature nerve dysfunction presents these findings context diabetes-induced degeneration mediated by alterations mitochondrial ultrastructure, physiology trafficking. Diabetes-induced calcium homeostasis...
OBJECTIVE—Peripheral neuropathy associated with type 2 diabetes (DPN) is not widely modeled. We describe unique features of DPN in diabetic Zucker fatty (ZDF) rats. RESEARCH DESIGN AND METHODS—We evaluated the structural, electrophysiological, behavioral, and molecular ZDF rats littermates over 4 months hyperglycemia. The status insulin signaling transduction molecules that might be interrupted selected survival-, stress-, pain-related was emphasized dorsal root ganglia (DRG) sensory...
Sensory neurons have the capacity to produce, release, and respond acetylcholine (ACh), but functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we reported that neurite outgrowth from were maintained under subsaturating neurotrophic factor conditions operates constraint is mediated by muscarinic receptor-dependent regulation mitochondrial function via AMPK. mice lacking ACh type 1 receptor (M1R) exhibited enhanced outgrowth,...
Diabetic sensorimotor polyneuropathy (DSPN) affects approximately half of diabetic patients leading to significant morbidity. There is impaired neurotrophic growth factor signaling, AMP-activated protein kinase (AMPK) activity and mitochondrial function in dorsal root ganglia (DRG) animal models type 1 2 diabetes. We hypothesized that sub-optimal insulin-like (IGF-1) signaling diabetes drives loss AMPK function, both contributing development DSPN. Age-matched control Sprague-Dawley rats...