A5083175277- Neuroinflammation and Neurodegeneration Mechanisms
- Neurological Disease Mechanisms and Treatments
- Neuroscience and Neuropharmacology Research
- Neurogenesis and neuroplasticity mechanisms
- Neurological Disorders and Treatments
- Alzheimer's disease research and treatments
- Traumatic Brain Injury and Neurovascular Disturbances
- Biochemical effects in animals
- S100 Proteins and Annexins
- Genomics, phytochemicals, and oxidative stress
- Nerve injury and regeneration
- Anesthesia and Neurotoxicity Research
- Tryptophan and brain disorders
- Genetics, Aging, and Longevity in Model Organisms
- Telomeres, Telomerase, and Senescence
- Traumatic Brain Injury Research
- Redox biology and oxidative stress
- Ion channel regulation and function
- Effects of Radiation Exposure
- Vitamin C and Antioxidants Research
- Neuroendocrine regulation and behavior
- Cerebrovascular and Carotid Artery Diseases
- MicroRNA in disease regulation
- Pain Mechanisms and Treatments
- Nuclear Receptors and Signaling
University of Edinburgh
2009-2023
University of Glasgow
1999-2006
Wellcome Centre for Molecular Parasitology
2002-2004
Southern General Hospital
2002
Ontario Institute for Cancer Research
1967
University of Toronto
1967
Abstract Alzheimer’s disease (AD) alters astrocytes, but the effect of Aß and Tau pathology is poorly understood. TRAP-seq translatome analysis astrocytes in APP/PS1 ß-amyloidopathy MAPT P301S tauopathy mice revealed that only influenced expression AD risk genes, both pathologies precociously induced age-dependent changes, had distinct overlapping signatures found human post-mortem astrocytes. Both an astrocyte signature involving repression bioenergetic translation machinery, induction...
Abstract Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells – astrocytes mature myelin-forming oligodendrocytes a determinant remyelination. Using vivo/ ex vitro rodent models, unbiased RNA sequencing, functional manipulation, human brain lesion analyses, discover...
Oligodendrocytes are critical for the development of plasma membrane and cytoskeleton axon. In this paper, we show that fast axonal transport is also dependent on oligodendrocyte. Using a mouse model hereditary spastic paraplegia type 2 due to null mutation myelin Plp gene, find progressive impairment in retrograde anterograde transport. Increased levels motor protein subunits associated with accumulation membranous organelles distal nodal complexes. cell transplantation, categorically...
It is currently unclear whether the GluN2 subtype influences NMDA receptor (NMDAR) excitotoxicity. We report that toxicity of NMDAR-mediated Ca2+ influx differentially controlled by cytoplasmic C-terminal domains GluN2B (CTD2B) and GluN2A (CTD2A). Studying effects acute expression GluN2A/2B-based chimeric subunits with reciprocal exchanges their CTDs revealed CTD2B enhances NMDAR toxicity, compared to CTD2A. Furthermore, vulnerability forebrain neurons in vitro vivo NMDAR-dependent lowered...
Mild traumatic brain injury (TBI) accounts for up to 80% of clinical TBI and can result in cognitive impairment white matter damage that may develop persist over several years. Clinically relevant models mild investigation neurobiological changes the development therapeutic strategies are poorly developed. In this study we investigated temporal profile axonal somal contribute impairments a mouse model TBI. Neuronal perikaryal (hematoxylin eosin Fluoro-Jade C), myelin integrity (myelin basic...
Understanding household behavior and its macro consequences for society is pivotal climate change adaptation. Yet, traditional policy decision-support models nature–society systems oversimplify human behavior. Using original modeling ...Despite the growing calls to integrate realistic in sustainability science models, representative rational agent prevails. This especially problematic adaptation that relies on actions at various scales: from ...
Abstract The nuclear mineralocorticoid receptor (MR), a high‐affinity for glucocorticoids, is highly expressed in the hippocampus where it underpins cognitive, behavioural and neuroendocrine regulation. Increased neuronal MR expression occurs early response to cellular injury vivo vitro associated with enhanced survival. To determine whether increased might be causal protecting against ischaemic damage we generated forebrain‐specific MR‐overexpressing transgenic mouse (MR‐Tg) under control...
Prophylactic pharmacological activation of astrocytic gene expression driven by the transcription factor Nrf2 boosts antioxidant defences and protects against neuronal loss in ischemia other disease models. However, role mediating endogenous neuroprotective responses is less clear. We recently showed that activated mild oxidative stress both rodent human astrocytes. Moreover, brief exposure to ischemic conditions was found activate vivo vitro , this contribute preconditioning. Here we show...
Abstract The cellular composition of individual hemopoietic spleen colonies has been studied using techniques which tested primarily for cell function rather than morphology. Erythroblastic cells were recognized by their capacity to incorporate radioiron, granulocytic content peroxidase‐positive material, and stem ability form in irradiated hosts. It was found that, 14 days after the initiation colonies, distribution these types among very heterogeneous, but that most contained detectable...
Cerebral small vessel disease (SVD) is a major contributor to stroke, cognitive impairment and dementia with limited therapeutic interventions. There critical need provide mechanistic insight improve translation between pre-clinical research the clinic. A 2-day workshop was held which brought together experts from several disciplines in cerebrovascular disease, cardiovascular biology, highlight current advances these fields, explore synergies scope for development. These proceedings summary...
The brain’s white matter is highly vulnerable to reductions in cerebral blood flow via mechanisms that may involve elevated microgliosis and pro-inflammatory pathways. In the present study, effects of severe hypoperfusion were investigated on function inflammation. Male C57Bl/6J mice underwent bilateral common carotid artery stenosis was assessed at seven days with electrophysiology response evoked compound action potentials (CAPs) corpus callosum. peak latency CAPs axonal refractoriness...
Abstract Background Chronic cerebral hypoperfusion causes damage to the brain’s white matter underpinning vascular cognitive impairment. Inflammation and oxidative stress have been proposed as key pathophysiological mechanisms of which transcription factor Nrf2 is a master regulator. We hypothesised that pathology, microgliosis, blood-brain barrier breakdown behavioural deficits induced by chronic would be exacerbated in mice deficient Nrf2. Methods Mice (male heterozygote or homozygous for...
Chronic cerebral hypoperfusion, a sustained modest reduction in blood flow, is associated with damage to myelinated axons and cognitive decline ageing. Oligodendrocytes (the myelin producing cells) their precursor cells (OPCs) may be vulnerable the effects of hypoperfusion some forms injury OPCs have potential respond repair by increased proliferation differentiation. Using mouse model we characterised acute long term responses oligodendrocytes corpus callosum. Following 3 days numbers...
Mouse models have shown that cerebral hypoperfusion causes white matter disruption and memory impairment relevant to the study of vascular cognitive dementia. The associated mechanisms include inflammation oxidative stress are proposed drive myelinated axons within hypoperfused matter. aim this was determine if increased endogenous anti-oxidant anti-inflammatory signalling in astrocytes protective a model mild hypoperfusion. Transgenically altered mice overexpressing transcription factor...
Protection of both grey and white matter is important for improvement in stroke outcome. In the present study ability a competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) antagonist to protect axons, oligodendrocytes, neuronal perikarya, was examined rodent model transient focal cerebral ischemia. SPD 502 (8-methyl-5-(4-( -dimethylsulfamoyl)phenyl)-6,7,8,9-tetrahydro-1H-pyrrolo[3,2h]-isoquinoline-2,3-dione-3-o(4-hydroxybutyricacid-2-yl)oxime) administered as an...
AMPA receptor potentiators enhance receptor-mediated glutamatergic neurotransmission and may have therapeutic potential as cognitive enhancers or antidepressants. The anatomical basis for the action of is unknown. aim this study was to determine effects biarylpropylsulfonamide potentiator, LY404187 (0.05 5 mg/kg subcutaneously), upon cerebral glucose utilization c-fos expression using 14 C-2-deoxglucose autoradiography immunocytochemistry. (0.5 mg/kg) produced significant elevations in 28 52...