A5044032139- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neuropharmacology Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Pluripotent Stem Cells Research
- Neonatal and fetal brain pathology
- MicroRNA in disease regulation
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Advanced Neuroimaging Techniques and Applications
- Anesthesia and Neurotoxicity Research
- Axon Guidance and Neuronal Signaling
- Mitochondrial Function and Pathology
- Epigenetics and DNA Methylation
- Circadian rhythm and melatonin
- RNA Research and Splicing
- Health and Medical Research Impacts
- Alzheimer's disease research and treatments
- Retinal Development and Disorders
- RNA regulation and disease
- Advanced MRI Techniques and Applications
- Photoreceptor and optogenetics research
- Neurological Disease Mechanisms and Treatments
- Adipose Tissue and Metabolism
- Cellular Mechanics and Interactions
- Immune cells in cancer
University of Cambridge
2015-2024
Wellcome/MRC Cambridge Stem Cell Institute
2015-2024
University of Iceland
2001-2024
Medical Research Council
2013-2023
FENS Kavli Network of Excellence
2015-2016
Bridge University
2009-2014
Wellcome Trust
2013
Stem Cell Institute
2011-2013
University College London
2005-2010
Stanford University
2005
Abstract Mutations in the cytosine‐5 RNA methyltransferase NSun2 cause microcephaly and other neurological abnormalities mice human. How post‐transcriptional methylation contributes to human disease is currently unknown. By comparing gene expression data with global methylomes patient fibroblasts NSun2‐deficient mice, we find that loss of increases angiogenin‐mediated endonucleolytic cleavage transfer RNAs ( tRNA ) leading an accumulation 5′ ‐derived small fragments. Accumulation fragments...
Oligodendrocyte progenitor cells (OPCs), which differentiate into myelinating oligodendrocytes during CNS development, are the main proliferative in adult brain. OPCs conventionally considered a homogeneous population, particularly with respect to their electrophysiological properties, but this has been debated. We show, by using single-cell recordings, that start out as population become functionally heterogeneous, varying both within and between brain regions age. These changes correlate...
Neuregulin switches oligodendrocytes between two modes of myelination: from a neuronal activity–independent mode to myelin-increasing, activity–dependent, mechanism that involves glutamate release and NMDA receptor activation.
Myelin regeneration can occur spontaneously in demyelinating diseases such as multiple sclerosis (MS). However, the underlying mechanisms and causes of its frequent failure remain incompletely understood. Here we show, using an in-vivo remyelination model, that demyelinated axons are electrically active generate de novo synapses with recruited oligodendrocyte progenitor cells (OPCs), which, early after lesion induction, sense neuronal activity by expressing AMPA...
Synapse loss correlates with cognitive decline in Alzheimer's disease (AD). Data from mouse models suggests microglia are important for synapse degeneration, but direct human evidence any glial involvement removal AD remains to be established. Here we observe astrocytes and brains contain greater amounts of synaptic protein compared non-disease controls, that proximity amyloid-β plaques the APOE4 risk gene exacerbate this effect. In culture, primary phagocytose patient-derived synapses more...
Abstract The role of remote astrocyte (AC) reaction to central or peripheral axonal insult is not clearly understood. Here we use a transgenic approach compare the direct influence normal with diminished AC reactivity on neuronal integrity and synapse recovery following extracranial facial nerve transection in mice. Our model allows straightforward interpretations AC–neuron signalling by reducing confounding effects imposed inflammatory cells. We show evidence that perineuronal reactive ACs...
Tauopathies, such as Alzheimer's disease, some cases of frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy, are characterized by aggregates the microtubule-associated protein tau, which linked to neuronal death disease development can be caused mutations in MAPT gene. Six tau isoforms present adult human brain they differ presence 3(3R) or 4(4R) C-terminal repeats. Only shortest 3R isoform is foetal brain. found affect binding microtubules 3R:4R ratio...
Adjusting the thickness and internodal length of myelin sheath is a mechanism for tuning conduction velocity axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) developing regulate formation around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10-positive oligodendrocytes, that endogenously released GABA, acting on GABAA receptors, greatly reduces number lineage cells. The decrease correlates with...
Abstract Light is extensively used to study cells in real time (live cell imaging), separate using fluorescence activated sorting (FACS) and control cellular functions with light sensitive proteins (Optogenetics). However, photo-sensitive molecules inside standard culture media generate toxic by-products that interfere viability when exposed light. Here we show primary from the rat central nervous system respond differently photo-toxicity, astrocytes microglia undergo morphological changes,...
In the central nervous system, electrical signals passing along nerve cells are speeded by called oligodendrocytes, which wrap with a fatty layer myelin. This is important for rapid information processing, and often lost in disease, causing mental or physical impairment multiple sclerosis, stroke, cerebral palsy spinal cord injury. The myelin speeds flow two ways, decreasing capacitance of cell increasing its membrane resistance, but little known about latter aspect function. By recording...
We have established and efficient system to specify NG2/PDGF-Ra/OLIG2+ oligodendrocyte precursor cells (OPCs) from human embryonic stem (hESCs) at low, physiological (3%) oxygen levels.This was achieved via both forebrain spinal cord origins, with up 98% of expressing NG2.Developmental insights reveal a critical role for fibroblast growth factor 2 (FGF-2) in OLIG2 induction ventral pathways.The OPCs mature vitro express O4 (46%) subsequently become galactocerebroside (GALC), O1, myelin basic...
Stem cell lines that faithfully maintain the regional identity and developmental potency of progenitors in human brain would create new opportunities neurobiology provide a resource for generating specialized neurons. However, to date, neural progenitor cultures derived from have either been short-lived or exhibit restricted, predominantly glial, differentiation capacity. Pluripotent stem cells are an alternative source, but ascertain definitively fidelity types generated solely <i>in...
The mediobasal hypothalamus (MBH; arcuate nucleus of the [ARH] and median eminence [ME]) is a key nutrient sensing site for production complex homeostatic feedback responses required maintenance energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation differentiation oligodendrocyte progenitors, leading to new oligodendrocytes in ME specifically. During this nutritional paradigm, perineuronal nets (PNNs), emerging regulators ARH metabolic functions,...
During brain anoxia or ischemia, a decrease in the level of ATP leads to sudden transmembrane ion gradients [anoxic depolarization (AD)]. This releases glutamate by reversing operation transporters, which triggers neuronal death. By whole-cell clamping CA1 pyramidal cells, we investigated energy stores that delay occurrence AD hippocampal slices when O 2 and glucose are removed. With glycolytic mitochondrial production blocked P12 slices, occurred ∼7 min at 33°C, reflecting time needed for...
Abstract Damage to oligodendrocytes caused by glutamate release contributes mental or physical handicap in periventricular leukomalacia, spinal cord injury, multiple sclerosis, and stroke, has been attributed activation of AMPA/kainate receptors. However, also activates unusual NMDA receptors oligodendrocytes, which can generate an ion influx even at the resting potential a physiological [Mg 2+ ]. Here, we show that clinically licensed receptor antagonist memantine blocks oligodendrocyte...