A5064591435- Nerve injury and regeneration
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Neurogenesis and neuroplasticity mechanisms
- Spinal Cord Injury Research
- CRISPR and Genetic Engineering
- MicroRNA in disease regulation
- Extracellular vesicles in disease
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- Neuroendocrine regulation and behavior
- Nerve Injury and Rehabilitation
- Wound Healing and Treatments
- Genetics, Aging, and Longevity in Model Organisms
- Nuclear Receptors and Signaling
- Genetic Neurodegenerative Diseases
- Neuroscience of respiration and sleep
- Tendon Structure and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Heart Rate Variability and Autonomic Control
- RNA Research and Splicing
- Pluripotent Stem Cells Research
- Amyotrophic Lateral Sclerosis Research
- Ocular Disorders and Treatments
University of Bristol
2012-2023
Oxford BioMedica (United Kingdom)
2003-2006
Wellcome Library
2006
Biomedica (Czechia)
2005
Bristol Royal Infirmary
2000-2003
Following peripheral axon injury, dysregulation of non-coding microRNAs (miRs) occurs in dorsal root ganglia (DRG) sensory neurons. Here we show that DRG neuron cell bodies release extracellular vesicles, including exosomes containing miRs, upon activity. We demonstrate miR-21-5p is released the exosomal fraction cultured following capsaicin activation TRPV1 receptors. Pure neuron-derived by are readily phagocytosed macrophages which an increase expression promotes a pro-inflammatory...
Following injury, dorsal root ganglion (DRG) neurons undergo transcriptional changes so as to adopt phenotypic that promote cell survival and axonal regeneration. Here we used a microarray approach profile in population of small noncoding RNAs known microRNAs (miRNAs) the L4 L5 DRG following sciatic nerve transection. Results showed 20 miRNA transcripts displayed significant change expression levels, with 8 miRNAs being altered by more than 1.5-fold. Using quantitative reverse transcription...
Evidence suggests that the acquisition of recognition memory depends upon CREB-dependent long-lasting changes in synaptic plasticity perirhinal cortex.The CREB-responsive microRNA miR-132 has been shown to regulate transmission and we set out investigate a role for this its underlying mechanisms. To end mediated specific overexpression selectively rat cortex demonstrated impairment short-term memory. This functional deficit was associated with reduction both long-term depression...
We have developed a non-primate-based lentiviral vector based on the equine infectious anemia virus (EIAV) for efficient gene transfer to central and peripheral nervous systems. Previously we demonstrated that pseudotyping vectors with rabies glycoprotein confers retrograde axonal transport these vectors. In present study successfully produced high-titer EIAV pseudotyped envelope glycoproteins from Rhabdovirus vesicular stomatitis (VSV) serotypes (Indiana Chandipura strains); [various...
Cerebral Dopamine Neurotrophic Factor (CDNF) and Mesencephalic Astrocyte-derived factor (MANF) are members of a recently discovered family neurotrophic factors (NTFs). Here, we used intranigral or intrastriatal lentiviral vector-mediated expression to evaluate their efficacy at protecting dopaminergic function in the 6-OHDA model Parkinson's disease (PD). In contrast well-studied Glial-Derived (GDNF), no beneficial effects were demonstrated by striatal overexpression either protein....
Abstract Albuminuria affects millions of people, and is an independent risk factor for kidney failure, cardiovascular morbidity death. The key cell that prevents albuminuria the terminally differentiated glomerular podocyte. Here we report evolutionary importance enzyme Glycogen Synthase Kinase 3 (GSK3) maintaining podocyte function in mice equivalent nephrocyte Drosophila . Developmental deletion both GSK3 isoforms (α β) murine podocytes causes late neonatal death associated with massive...
In acute experiments, we demonstrated previously that nitric oxide (NO) donors exogenously applied to the nucleus tractus solitarii (NTS) depressed baroreceptor cardiac reflex. this study, determined a role for endogenous endothelial synthase (eNOS) activity in NTS chronically regulating reflex function conscious rats. A recombinant adenoviral vector directing expression of truncated form eNOS was microinjected bilaterally into inhibit activity. Arterial pressure monitored continuously using...
Spinal cord injury often results in permanent and devastating neurological deficits disability. This is due to the limited regenerative capacity of neurones central nervous system (CNS). We recently demonstrated that a transcription factor retinoic acid receptor beta2 (RARbeta2) promoted axonal regeneration adult sensory located peripherally. However, it not known if RARbeta2 can promote cortical CNS. Here, we demonstrate delivery via lentiviral vector dissociated significantly enhances...
Abstract Although viral vector‐mediated delivery of glial cell‐line derived neurotrophic factor (GDNF) to the brain has considerable potential as a neuroprotective strategy in Parkinson's disease (PD), its ability protect complex motor functions relevant human condition yet be established. In this study, we used an operant task that assesses selection, initiation and execution lateralized nose‐pokes Lister Hooded rats assess efficacy with which behaviours are protected against neurotoxic...
Following trauma of the adult brain or spinal cord injured axons central neurons fail to regenerate if intact display only limited anatomical plasticity through sprouting. Adult cortical forming corticospinal tract (CST) normally have low levels neuronal calcium sensor-1 (NCS1) protein. In primary cultured neurons, lentivector-induced overexpression NCS1 induces neurite sprouting associated with increased phospho-Akt levels. When PI3K/Akt signalling pathway was pharmacologically inhibited...
Background Gap junction communication has been shown in glial and neuronal cells it is thought they mediate inter- intra-cellular communication. Connexin 36 (Cx36) expressed extensively the developing brain, with levels peaking at P14 after which its fall expression becomes entirely neuronal. These other data have led to hypothesis that Cx36 may direct coupling neurogenesis during development. Methodology/Principal Findings To investigate function we used a neurosphere model of cell...
Safe hydrogel delivery requires stiffness-matching with host tissues to avoid iatrogenic damage and reduce inflammatory reactions. Hydrogel-encapsulated cell is a promising combinatorial approach spinal cord injury therapy, but lack of in vivo clinical stiffness measurements barrier their use clinics. We demonstrate that ultrasound elastography - non-invasive, clinically established tool can be used measure intraoperatively canines spontaneous injury. In line recent experimental reports, our...
Abstract The NO‐cGMP pathway has emerged as a neuroprotective signaling system involved in communication between neurons and glia. We have previously shown that axotomy or nerve growth factor (NGF)‐deprivation of dorsal root ganglion (DRG) leads to increased production NO at the same time an increase cGMP their satellite glia cells. Blockade its receptor, synthesizing enzyme soluble guanylate cyclase (sGC), results apoptosis now show co‐culture neonatal DRG with either Schwann cells...
<h2>Abstract</h2> In this study, we evaluated the possible use of lentiviral vectors in treatment neuropathic pain. We chose to administer GDNF-expressing because known beneficial effect trophic factor alleviation pain adult rodents. Lentiviral expressing either GDNF or control, green fluorescent protein β-galactosidase, were injected unilaterally into spinal dorsal horn 5 weeks before a nerve ligation was induced (or sham surgery for controls). observed that intraspinally administered...
Nutrient deprivation during ischemia leads to severe insult neurons causing widespread excitotoxic damage in specific brain regions such as the hippocampus. One possible strategy for preventing neurodegeneration is express therapeutic proteins protect against excitotoxicity. We investigated utility of equine infectious anemia virus (EIAV)-based vectors genetic tools delivery an vivo excitotoxicity model. The efficacy these at cellular loss target areas following was also assessed. EIAV...
Several matrix metalloproteinases (MMPs), including MMP-1, -3, and -9, mediate destruction during chronic inflammatory diseases such as arthritis atherosclerosis. MMP up-regulation by cytokines involves interactions between several transcription factors, activator protein-1 nuclear factor kappaB (NF-kappaB). The upstream regulatory pathways are less well understood. We investigated the role of isoforms protein kinase C (PKC) in basic fibroblast growth factor- interleukin-1alpha-mediated...
ABSTRACT Heart failure and hypertension are associated with increases in angiotensin II (ANG II) activity. One brain area where ANG effects may be particularly important these situations is the nucleus of solitary tract (NTS). Located dorsomedial medulla, NTS termination site baroreceptor afferents essential for mediating baroreflex. In hypertensive animals baroreflex impaired; this reversed by antagonizing AT 1 receptors NTS. Recently, we showed that depressant action mediated activation...
Due to the complexity of brain function and difficulty in monitoring alterations neuronal gene expression, potential lentiviral therapy vectors treat disorders CNS has been difficult fully assess. In this study, we have assessed utility a third-generation equine infectious anemia virus (EIAV) Brattleboro rat model diabetes insipidus, which mutation arginine vasopressin (AVP) results production nonfunctional mutant AVP precursor protein. Importantly, by using it is possible monitor success...
Vectors based on lentiviruses are opening up new approaches for the treatment of neurodegenerative diseases. Currently, equine infectious anaemia virus (EIAV) vector is one most attractive gene delivery systems with respect to neuronal tropism. The aim was validate EIAV-lentiviral vectors as a system neurotrophic factor genes in an animal model Parkinson's disease. EIAV carrying glial cell line-derived (GDNF) unilaterally injected into rat striatum and above substantia nigra (SN). One week...