A5005548202- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Immune Response and Inflammation
- Multiple Sclerosis Research Studies
- Neurogenesis and neuroplasticity mechanisms
- Amyotrophic Lateral Sclerosis Research
- Single-cell and spatial transcriptomics
- RNA regulation and disease
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- MicroRNA in disease regulation
- Advanced biosensing and bioanalysis techniques
- Genetic Associations and Epidemiology
- Tryptophan and brain disorders
- Autophagy in Disease and Therapy
- Neuroscience and Neuropharmacology Research
- Infant Nutrition and Health
- Hereditary Neurological Disorders
- Vector-borne infectious diseases
- Cytokine Signaling Pathways and Interactions
- Neurogenetic and Muscular Disorders Research
- Heat shock proteins research
- Glaucoma and retinal disorders
- Neonatal and fetal brain pathology
- Nerve injury and regeneration
Amsterdam Neuroscience
2018-2024
Biomedical Primate Research Centre
2023-2024
Amsterdam UMC Location Vrije Universiteit Amsterdam
2017-2023
Amsterdam University Medical Centers
2018-2023
Netherlands Institute for Neuroscience
2021
University of Amsterdam
2021
Anna Needs Neuroblastoma Answers
2020
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...
Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration the central nervous system (CNS). The capacity microglia to clear tissue debris essential for maintaining restoring CNS homeostasis. This diminishes with age, age strongly associates MS disease progression, although underlying mechanisms are still largely elusive. Here, we demonstrate that recovery from murine model dependent on ability debris....
The 18 kDa translocator protein (TSPO) is increasingly used to study brain and spinal cord inflammation in degenerative diseases of the CNS such as multiple sclerosis. enhanced TSPO PET signal that arises during disease widely considered reflect activated pathogenic microglia, although quantitative neuropathological data support this interpretation have not been available. With increasing interest role chronic microglial activation sclerosis, characterising cellular neuropathology associated...
Abstract To monitor innate immune responses in the CNS, 18 kDa Translocator protein (TSPO) is a frequently used target for PET imaging. The frequent assumption that increased TSPO expression human CNS reflects pro‐inflammatory activation of microglia has been extrapolated from rodent studies. However, does not increase activated vitro. Studies multiple sclerosis (MS) lesions reveal restricted to microglia/macrophages, but also present homeostatic or reparative microglia. Here, we...
Abstract Microglia are the resident innate immune cells of central nervous system (CNS) parenchyma. To determine impact microglia on disease development and progression in neurodegenerative neuroinflammatory diseases, it is essential to distinguish from peripheral macrophages/monocytes, which eventually equally recruited. It has been suggested that transmembrane protein 119 (TMEM119) serves as a reliable marker discriminates blood‐derived macrophages human murine brain. Here, we investigated...
Abstract Multiple sclerosis (MS) is a disease of the central nervous system that characterized by inflammation and focal areas demyelination, ultimately resulting in axonal degradation neuronal loss. Several lines evidence point towards role for microglia other brain macrophages initiation progression, but exactly how lesion formation triggered currently unknown. Here, we early changes MS tissue through transcriptomic analysis normal appearing white matter (NAWM). We found NAWM was enriched...
Coronavirus disease 2019 (COVID-19) patients initially develop respiratory symptoms, but they may also suffer from neurological symptoms. People with long-lasting effects after acute infections severe syndrome coronavirus 2 (SARS-CoV-2), i.e., post-COVID or long COVID, experience a variety of manifestations. Although we do not fully understand how SARS-CoV-2 affects the brain, neuroinflammation likely plays role.
Abstract Targeting myeloid cells, especially microglia, for the treatment of neuroinflammatory diseases such as multiple sclerosis (MS), is underappreciated. Our in silico drug screening reveals topoisomerase 1 (TOP1) inhibitors promising candidates microglial modulation. We show that TOP1 highly expressed conditions, and inhibition using camptothecin (CPT) its FDA‐approved analog topotecan (TPT) reduces inflammatory responses microglia/macrophages ameliorates neuroinflammation vivo ....
Abstract The lack of understanding the cellular and molecular basis clinical genetic heterogeneity in progressive multiple sclerosis (MS) has hindered search for new effective therapies. Here, to address this gap, we analysed 632,000 single nuclei RNAseq profiles 156 brain tissue samples, comprising white matter (WM) lesions, normal appearing WM, grey (GM) lesions GM from 54 MS patients 26 controls. We observed expected changes overall neuronal glial numbers previously described within...
Abstract Human brain experimental models recapitulating age- and disease-related characteristics are lacking. There is urgent need for human-specific tools that model the complex molecular cellular interplay between different cell types to assess underlying disease mechanisms test therapies. Here we present an adapted ex vivo organotypic slice culture method using human post-mortem tissue cultured at air-liquid interface also study white matter. We assessed whether these slices recapitulate...
Aims Amyotrophic lateral sclerosis (ALS) is a chronic neurodegenerative disease characterized by progressive loss of motor neurons, muscle weakness, spasticity, paralysis and death usually within 2–5 years onset. Neuroinflammation hallmark ALS pathology activation glial cells, which respond upregulating small heat shock proteins (HSPBs), but the exact underlying pathological mechanisms are still largely unknown. Here, we investigated association between duration, lower neuron loss,...
Disability in multiple sclerosis (MS) is considered primarily a result of axonal loss. However, correlation with spinal cord cross-sectional area-a predictor disability-is poor, questioning the unique role We investigated degree synaptic loss postmortem cords (18 chronic MS, 8 healthy controls) using immunohistochemistry for synaptophysin and synapsin. Substantial (58-96%) synapses throughout was detected, along moderate (47%) anterior horn neurons, notably demyelinating MS lesions. conclude...
Optic neuritis, a primary clinical manifestation commonly observed in multiple sclerosis (MS), is major factor leading to permanent loss of vision. Despite decreased vision (optic neuritis), diplopia, and nystagmus, the immunopathology optic nerve MS unclear. Here, we have characterized pathology large cohort cases (n = 154), focusing on immune responses sub-cohort 30) control 6) cases. Immunohistochemistry was used characterize myeloid (HLA-DR, CD68, Iba1, TMEM119, P2RY12) adaptive cells...
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 Objective Despite progress in treating relapsing multiple sclerosis ( MS ), effective inhibition of nonrelapsing progressive is an urgent, unmet, clinical need. Animal models , such as experimental autoimmune encephalomyelitis EAE provide valuable tools to examine the mechanisms contributing disease and may be important for developing rational therapeutic approaches treatment . It has been suggested that myelin oligodendrocyte glycoprotein MOG ) peptide residues 35‐55 )‐induced...
Multiple sclerosis (MS) is a chronic neurodegenerative disease characterized by demyelination, inflammation and neurodegeneration throughout the central nervous system. Although spinal cord pathology an important factor contributing to progression, few studies have examined MS lesions in how they differ from brain lesions. In this study we compared white (WM) grey (GM) matter control tissues, focusing on small heat shock proteins (HSPB) HSP16.2. Western blotting was used examine protein...
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. For the first time, we show that TSPO gene protein expression increases activated microglia mouse brain disease models postmortem, does not change a non-human primate (Callithrix jacchus) model or common...