A5007880093- Pain Mechanisms and Treatments
- Nerve injury and regeneration
- Neuropeptides and Animal Physiology
- Ion Channels and Receptors
- Cannabis and Cannabinoid Research
- Neuroscience of respiration and sleep
- Mitochondrial Function and Pathology
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Gastrointestinal motility and disorders
- Eicosanoids and Hypertension Pharmacology
- Asthma and respiratory diseases
- Neuroscience and Neuropharmacology Research
- Fatty Acid Research and Health
- Receptor Mechanisms and Signaling
- Respiratory and Cough-Related Research
- Genetic Neurodegenerative Diseases
- Stress Responses and Cortisol
- Signaling Pathways in Disease
- MicroRNA in disease regulation
- Botulinum Toxin and Related Neurological Disorders
- Neuroendocrine regulation and behavior
- Hereditary Neurological Disorders
- Restless Legs Syndrome Research
- Cancer-related molecular mechanisms research
Queen Mary University of London
2008-2021
Universidad de Londres
2007
St Thomas' Hospital
1995-1996
University of Rochester
1988-1990
Several lines of evidence suggest that neurotrophin administration may be some therapeutic benefit in the treatment peripheral neuropathy. However, a third sensory neurons do not express receptors for neurotrophins. These are small diameter and can identified by binding lectin IB4 expression enzyme thiamine monophosphatase (TMP). Here we show these receptor components glial-derived neurotrophic factor (GDNF) signaling (RET, GFRα-1, GFRα-2). In lumbar dorsal root ganglia, virtually all...
Blood–brain barrier (BBB) dysfunction is a hallmark of neurological conditions such as multiple sclerosis (MS) and stroke. However, the molecular mechanisms underlying neurovascular during BBB breakdown remain elusive. MicroRNAs (miRNAs) have recently emerged key regulators pathogenic responses, although their role in central nervous system (CNS) microvascular disorders largely unknown. We identified miR-155 critical miRNA neuroinflammation at BBB. expressed unit individuals with MS mice...
An extensive protein–protein interaction network has been identified between proteins implicated in inherited ataxias. The protein sacsin, which is mutated the early-onset neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix-Saguenay, a node this interactome. Here, we have established neuronal expression sacsin and functionally characterized domains 4579 amino acid protein. Sacsin most highly expressed large neurons, particularly within brain motor systems, including...
Retinoic acid receptors (RARs), retinoid X (RXRs), and peroxisome proliferator-activated (PPARs) are transcription factors involved in many cellular processes, such as learning memory. RAR RXR mRNA levels decrease with ageing, the decreases can be reversed by retinoic treatment, which also alleviates age-related memory deficits. The omega-3 fatty acids eicosapentaenoic (EPA) docosahexaenoic (DHA) have neuroprotective effects aged brain endogenous ligands of PPAR. We investigated whether...
Glial cell line-derived neurotrophic factor (GDNF) has potent trophic effects on adult sensory neurons after nerve injury and is one of a family proteins that includes neurturin, persephin, artemin. Sensitivity to these factors conferred by receptor complex consisting ligand binding domain (GFRα1–GFRα4) signal transducing RET. We have investigated the normal expression GDNF components within response injury. In rats, RET GFRα1 were expressed in subpopulation both small- large-diameter...
Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic states. Endocannabinoids (ECs) are present in the cord, and inhibit nociceptive processing; levels ECs may be altered by which modulate turnover endocannabinoids vitro. Here, we investigate effect minocycline, an inhibitor activated microglia, on anandamide 2-arachidonoylglycerol (2-AG), related compound N-palmitoylethanolamine (PEA), cord. Selective nerve ligation (SNL) rats resulted mechanical...
Chronic neuropathic pain affects millions of individuals worldwide, is typically long-lasting, and remains poorly treated with existing therapies. Neuropathic arising from peripheral nerve lesions known to be dependent on the emergence spontaneous evoked hyperexcitability in damaged nerves. Here, we report that potassium channel subunit Kv9.1 expressed myelinated sensory neurons, but absent small unmyelinated neurons. expression was strongly rapidly downregulated following axotomy, a time...
NaV1.9 regulates normal colonic afferent mechanosensation and is required for hypersensitivity to noxious inflammatory mediators those derived from bowel disease tissues. Chronic visceral pain affects millions of individuals worldwide remains poorly understood, with current therapeutic options constrained by gastrointestinal adverse effects. Visceral strongly associated inflammation distension the gut. Here we report that voltage-gated sodium channel subtype expressed in half gut-projecting...
Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) emerged anti-inflammatory molecule by inhibiting activity various cell types, but its effect BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a...
Docosahexaenoic acid (DHA) is an ω-3 polyunsaturated fatty that essential in brain development and has structural signaling roles. Acute DHA administration neuroprotective promotes functional recovery animal models of adult spinal cord injury (SCI). However, the mechanisms underlying this have not been fully characterized. Here we investigated effects acute intravenous bolus delivered after SCI characterized DHA-induced neuroplasticity within injured cord. We found robust sprouting uninjured...
Activation of visceral nociceptors by inflammatory mediators contributes to hypersensitivity and abdominal pain associated with many gastrointestinal disorders. Purine pyrimidine nucleotides (e.g., ATP UTP) are strongly implicated in this process following their release from epithelial cells during mechanical stimulation the gut, immune inflammation. Actions mediated through both ionotropic P2X receptors metabotropic P2Y receptors. receptor activation causes excitation afferents; however,...
Abstract Activating transcription factor‐3 (ATF3) is a member of the ATF/CREB factor superfamily and induced in dorsal root ganglion (DRG) cells after nerve injury. In order to study regulation ATF3, we have examined effect growth (NGF) glial cell line‐derived neurotrophic (GDNF) on ATF3 expression. untreated rats, sciatic transection immunoreactivity 82% L4 DRG at 14 days axotomy. Intrathecal delivery NGF or GDNF for 2 weeks commencing immediately injury reduced expression 35 23% cells,...
Peripheral nerve injuries caused by trauma are associated with increased sensory neuron excitability and debilitating chronic pain symptoms. Axotomy-induced alterations in the function of ion channels thought to largely underlie pathophysiology these phenotypes. Here, we characterise mRNA distribution Kv2 family members rat dorsal root ganglia (DRG) describe a link between modulation excitability. Kv2.1 Kv2.2 were amply expressed cells all sizes, being particularly abundant medium-large...
The neurodegenerative disease autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is caused by loss function sacsin, a modular protein that required for normal mitochondrial network organization. To further understand cellular consequences we performed microarray analyses in sacsin knockdown cells and ARSACS patient fibroblasts. This identified altered transcript levels oxidative phosphorylation stress genes. These changes gene networks were validated quantitative reverse...
Neuronal pentraxin II (NPTX2) is the most highly upregulated gene in Parkinsonian substantia nigra based on our whole genome expression profiling results. We show here that it a novel component of Lewy bodies and neurites sporadic Parkinson's disease (PD). NPTX2 also known as neuronal activity-regulated protein (Narp), which secreted involved long-term plasticity. Narp further regulates AMPA receptors have been found to mediate selective non-apoptotic cell death dopaminergic neurons....
Endocannabinoids and some phytocannabinoids bind to CB1 CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) the orphan G protein fifty-five (GPR55). Studies using C57BL/10 C57BL/6 (Cnr2tm1Zim) knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies Biozzi ABH often failed show any treatment either agonism or antagonism on inhibition T cell autoimmunity....
Abstract Calcitonin gene‐related peptide (CGRP) is expressed at high levels in roughly 50% of spinal sensory neurons and plays a role peripheral vasodilation as well nociceptive signalling the cord. Spinal motoneurons express low CGRP; motoneuronal CGRP thought to be involved end‐plate plasticity have trophic effects on target muscle cells. As both receptors for glial cell line‐derived neurotrophic factor (GDNF) we sought determine whether was regulated by GDNF. Rats were treated...
Abstract In this study, we have investigated the effects of artemin (ARTN), one glial cell line‐derived neurotrophic factor (GDNF) family factors, on C‐fibres following nerve injury in adult rat. GDNF receptor alpha (GFRα) 3, ligand binding domain ARTN receptor, is expressed 34% dorsal root ganglion (DRG) cells, predominantly peptidergic population and a proportion isolectin B4 (IB4)‐binding population. Interestingly, only 30% GFRα3‐expressing DRG cells co‐expressed RET (the signal...
<i>Background:</i> We previously found many transient receptor potential vanilloid subtype 1 (TRPV1) axons in the tracheal smooth muscle and epithelium of guinea pig airway. One report indicates that number TRPV1 is significantly increased patients with cough variant asthma. <i>Aim:</i> To determine whether distribution airways altered pigs an allergic phenotype. <i>Methods:</i> Ten were assigned to 2 groups a double-blind study. Five animals sensitized...
C-fiber sensory neurons comprise nociceptors and smaller populations of cells detecting innocuous thermal light tactile stimuli. Markers identify subpopulations these cells, aiding our understanding their physiological roles. The transient receptor potential vanilloid 1 (TRPV1) cation channel is characteristic polymodal sensitive to noxious heat, irritant vanilloids, protons. By using immunohistochemistry, in situ hybridization, retrograde tracing, we anatomically characterize a small...