A5084713188- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Multiple Sclerosis Research Studies
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Alzheimer's disease research and treatments
- Immune cells in cancer
- Neurobiology and Insect Physiology Research
- Immune Response and Inflammation
- Genetics and Neurodevelopmental Disorders
- Neural dynamics and brain function
- Physiological and biochemical adaptations
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- RNA Interference and Gene Delivery
- Mesenchymal stem cell research
- Ion channel regulation and function
- Tryptophan and brain disorders
- Neurological Disease Mechanisms and Treatments
- Ion Transport and Channel Regulation
- Signaling Pathways in Disease
- Endoplasmic Reticulum Stress and Disease
- Spinal Cord Injury Research
- Cytokine Signaling Pathways and Interactions
- Photoreceptor and optogenetics research
University of Edinburgh
2010-2025
MRC Centre for Regenerative Medicine
2010-2025
UK Dementia Research Institute
2021-2025
Brandeis University
2018-2024
Mott MacDonald (United Kingdom)
2021-2023
Amsterdam University Medical Centers
2022
Amsterdam UMC Location Vrije Universiteit Amsterdam
2022
National Institutes of Health
2022
Tufts University
2014-2016
Universidad Autónoma de Occidente
2012
Abstract The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical and astrocytes from closely related species, followed by RNA-seq in silico species separation. This approach uncovers wide programme of neuron-induced gene expression, involving Notch signalling, which drives maintains maturity neurotransmitter uptake function, conserved human development, disrupted neurodegeneration. Separately, hundreds...
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 Microglial activation plays central roles in neuroinflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18 kDa Translocator Protein (TSPO) is widely used for localising inflammation vivo, but its quantitative interpretation remains uncertain. We show that TSPO expression increases activated microglia mouse brain disease models does not change a non-human primate model or common human describe genetic divergence the gene promoter, consistent with...
Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in circuitry are associated with TBI, the precise mechanisms by which leads to epileptiform network activity unknown. Using controlled cortical impact (CCI) as model of we examined how excitability and glutamatergic signaling was altered following injury. We optically mapped glutamate using FRET-based biosensors, while simultaneously recording field potentials acute slices 2–4...
The pathological correlate of clinical disability and progression in multiple sclerosis is neuronal axonal loss; however, the underlying mechanisms are unknown. Abnormal phosphorylation tau a common feature some neurodegenerative disorders, such as Alzheimer's disease. We investigated presence hyperphosphorylation its relationship with loss chronic experimental autoimmune encephalomyelitis (CEAE) brain samples from patients secondary progressive sclerosis. report novel finding abnormal CEAE....
Tau protein in a hyperphosphorylated state makes up the intracellular inclusions of several neurodegenerative diseases, including Alzheimer's disease and cases frontotemporal dementia. Mutations cause familial forms dementia, establishing that dysfunction tau is sufficient to neurodegeneration Transgenic mice expressing human mutant neurons exhibit essential features tauopathies, abundant filaments composed tau. Here we show previously described mouse line transgenic for P301S exhibits an...
ABSTRACT The central nervous system hosts parenchymal macrophages, known as microglia, and non-parenchymal collectively termed border-associated macrophages (BAMs). Microglia, but not BAMs, were reported to be absent in mice lacking a conserved Csf1r enhancer: the fms-intronic regulatory element (FIRE). However, it is unknown whether FIRE deficiency also impacts BAM arrival and/or maintenance. Here, we show that ventricular of brain, including Kolmer's epiplexus are Csf1rΔFIRE/ΔFIRE mice....
Myelination is essential for central nervous system (CNS) formation, health, and function. Emerging evidence of oligodendrocyte heterogeneity in health disease divergent CNS gene expression profiles between mice humans supports the development experimentally tractable human myelination systems. Here, we developed iPSC-derived myelinating organoids ("myelinoids") quantitative tools to study from oligodendrogenesis through compact myelin formation myelinated axon organization. Using...
Bone morphogenetic proteins (BMPs) and their endogenous inhibitors, including noggin, chordin follistatin, have roles in pattern formation fate specification of neuronal glial cells during nervous system development. We examined influence on reactions the injured central (CNS). show that penetrating injuries to brain spinal cord resulted upregulation BMP-2/4, BMP-7, with latter being expressed almost exclusively by reactive astrocytes at injury site, we vitro produce noggin. As BMPs been...
The activity of neuronal circuits depends on the properties constituent neurons and their underlying synaptic intrinsic currents. We describe effects extreme changes in extracellular pH – from 5.5 to 10.4 two central pattern generating networks, stomatogastric cardiac ganglia crab, Cancer borealis. Given that physiological ion channels are known be sensitive within range tested, it is surprising these rhythms generally remained robust 6.1 8.8. sensitivity was highly variable between animals...
Resilience to environmental fluctuations is important for all animals. It common that animals encounter multiple stressful events at the same time, cumulative impacts of which are largely unknown. This study examines effects temperature and pH on nervous system crabs live in fluctuating environments Northern Atlantic Ocean. The ranges tolerance one perturbation, temperature, reduced under influence a second, pH.
The Fragile X Messenger Ribonucleoprotein (FMRP) is an RNA binding protein that regulates the translation of multiple mRNAs and expressed by neurons glia in mammalian brain. Loss FMRP leads to fragile syndrome (FXS), a common inherited form intellectual disability autism. While most research has been focusing on neuronal contribution FXS pathophysiology, role glia, particularly oligodendrocytes, largely unknown. individuals are characterized white matter changes, which imply impairments...
Multiple Sclerosis has two clinical phases reflecting distinct but inter-related pathological processes: focal inflammation drives the relapse-remitting stage and neurodegeneration represents principal substrate of secondary progression. In contrast to increasing number effective anti-inflammatory disease modifying treatments for disease, absence therapies progressive a major unmet need. This raises unanswered question whether elimination relapses will prevent subsequent progression if so...
Abstract Introduction Neuroinflammation, which contributes to neurodegeneration, is a consistent hallmark of dementia. Emerging evidence suggests that systemic inflammation also disease progression. Methods The ability systemically administered lipopolysaccharide (LPS ‐ 500 μg/kg) effect acute and chronic behavioural changes in C57BL/6 P301S tauopathy mice was assessed. Markers pathology were assessed the brain spinal cord. Results display regional microgliosis. Systemic LPS treatment...
Abstract Microglial activation plays central roles in neuro-inflammatory and neurodegenerative diseases. Positron emission tomography (PET) targeting 18kDa Translocator Protein (TSPO) is widely used for localising inflammation vivo , but its quantitative interpretation remains uncertain. We show that TSPO expression increases activated microglia mouse brain disease models does not change a non-human primate model or common neuroinflammatory human describe genetic divergence the gene...
Abstract Background Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly of the central nervous system (CNS). Improvements in biosafety viral are paramount lentiviral move into human clinical trials. This study investigates packaging relationship between transfer (vector) and Gag-Pol expression constructs HIV-1, HIV-2 SIV. Cross-packaged expressing GFP were assessed RNA packaging, vector titre their ability transduce rat primary glial...