A5072144154- Neurogenesis and neuroplasticity mechanisms
- Nerve injury and regeneration
- Blood properties and coagulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Pluripotent Stem Cells Research
- Epigenetics and DNA Methylation
- Cell Adhesion Molecules Research
- MicroRNA in disease regulation
- Multiple Sclerosis Research Studies
- Skin and Cellular Biology Research
- Tissue Engineering and Regenerative Medicine
- RNA regulation and disease
- Cellular Mechanics and Interactions
- RNA Research and Splicing
- Alzheimer's disease research and treatments
- Microtubule and mitosis dynamics
- Immune cells in cancer
- Chromosomal and Genetic Variations
- Tendon Structure and Treatment
- Alkaloids: synthesis and pharmacology
- Bone health and treatments
- Protease and Inhibitor Mechanisms
- Nuclear Receptors and Signaling
- Transgenic Plants and Applications
- Extracellular vesicles in disease
University Medical Center Utrecht
2015-2020
Utrecht University
2015-2020
Netherlands Institute for Neuroscience
2011-2017
Heidelberg University
2017
University Hospital Heidelberg
2017
Amsterdam UMC Location Vrije Universiteit Amsterdam
2008-2015
Royal Netherlands Academy of Arts and Sciences
2011-2015
Royal Academy of Art
2014
Vrije Universiteit Amsterdam
1990-2013
Center for Neurosciences
2008-2011
Glioblastoma multiforme (GBM) is the most common primary brain tumor and without exception lethal. GBMs modify immune system, which contributes to aggressive nature of disease. Particularly, cells monocytic lineage, including monocytes, macrophages microglia, are affected. We investigated influence GBM-derived extracellular vesicles (EVs) on phenotype cells. Proteomic profiling showed GBM EVs be enriched with proteins functioning in matrix interaction leukocyte migration. appeared skew...
Remyelination following central nervous system demyelination is essential to prevent axon degeneration. However, remyelination ultimately fails in demyelinating diseases such as multiple sclerosis. This failure of likely mediated by many factors, including changes the extracellular signalling environment. Here, we examined expression matrix molecule fibronectin on injury and how this affects oligodendrocytes progenitors. In toxin-induced lesions undergoing efficient remyelination, was...
Vitamin D deficiency has been implicated as a risk factor for multiple sclerosis (MS), but how vitamin metabolism affects MS pathophysiology is not understood. We studied the expression of receptor (VDR) and related enzymes, including 1,25(OH)2D-24-hydroxylase (24-OHase; CYP24A1) 25(OH)D-1α-hydroxylase (CYP27B1), in CNS tissues 39 patients 20 controls primary human glial cells vitro. In control normal-appearing white matter (NAWM), nuclear VDR immunostaining was observed oligodendrocyte-like...
There are many indications that neurogenesis is impaired in Parkinson's disease, which might be due to a lack of dopamine the subventricular zone. An impairment may have negative consequences for development new therapeutic approaches as neural stem cells potential source endogenous repair. In this study, we examined zone 10 patients with disease and age- sex-matched controls proliferation cell numbers. We also included five cases incidental Lewy body showed pathology but no clinical...
Microglia are key players in the central nervous system health and disease. Much pioneering research on microglia function has been carried out vivo with use of genetic animal models. However, to fully understand role neurological psychiatric disorders, it is crucial study primary human from brain donors. We have developed a rapid procedure for isolation pure autopsy tissue using density gradient centrifugation followed by CD11b-specific cell selection. The protocol can be completed 4 h, an...
The basis of gender differences in the prevalence and clinical progression multiple sclerosis (MS) is not understood. Here, we identify gender-specific responses steroid synthesis signaling brains MS patients as possible contributors to these differences. We investigated gene expression changes pathways inflammatory cytokines lesions normal-appearing white matter (NAWM) male female (n=21) control NAWM (n=14) using quantitative polymerase chain reaction (25 lesions, 21 NAWM, 14 NAWM)...
Autoantibodies and complement opsonization have been implicated in the process of demyelination major human CNS demyelinating disease multiple sclerosis (MS), but scavenger receptors (SRs) may also play pathogenetic roles. We characterized SR mRNA protein expression postmortem brain tissue from 13 MS patients relation to active demyelination. CD68, chemokine (C-X-C motif) ligand 16 (CXCL16), class A macrophage SR(SR-AI/II), LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1),...
Glial Fibrillary Acidic Protein (GFAP) is the main intermediate filament in astrocytes and regulated by epigenetic mechanisms during development. We demonstrate that histone acetylation controls GFAP expression also mature astrocytes. Inhibition of deacetylases (HDACs) with Trichostatin-A or Sodium-butyrate reduced primary human astrocytoma cells. Since splicing occurs co-transcriptional, we investigated whether changes ratio between canonical isoform GFAPα alternative GFAPδ splice-variant....
Glial fibrillary acidic protein (GFAP) is the characteristic intermediate filament (IF) in astrocytes. Expression of its main isoforms, GFAPα and GFAPδ, varies astrocytes astrocytoma implying a potential regulatory role astrocyte physiology pathology. An IF-network dynamic structure has been functionally linked to cell motility, proliferation, morphology. There constant exchange IF-proteins with network. To study differences properties we performed fluorescence recovery after photobleaching...
Abstract Neural progenitor cells (NPCs) in the subventricular zone (SVZ) hold promise for future therapy neurodegenerative disorders, because stimulation of adult neurogenesis could potentially restore function degenerating neurons and glia. To obtain more knowledge on these NPCs, we developed a method to specifically isolate NPCs from postmortem human brains based expression specific neural stem/progenitor cell marker glial fibrillary acidic protein δ (GFAPδ). An extensive immunophenotyping...
An important neuropathological feature of neuroinflammatory processes that occur during e.g. Multiple Sclerosis (MS) is the formation an astroglial scar. Astroglial scar facilitated by interaction between astrocytes and extracellular matrix proteins (ECM) such as fibronectin. Since there evidence indicating glial scars strongly inhibit both axon growth (re)myelination in brain lesions, it to understand factors contribute ECM proteins. Tissue Transglutaminase (TG2) a multifunctional enzyme...
Glial fibrillary acidic protein (GFAP) is an intermediate filament expressed in astrocytes and neural stem cells. The GFAP gene alternatively spliced, expression of highly regulated during development, on brain damage, neurodegenerative diseases. GFAPα the canonical splice variant all GFAP-positive In human brain, spliced transcript GFAPδ marks specialized astrocyte populations, such as subpial neurogenic subventricular zone. We here show that shifting isoform ratio favor astrocytoma cells,...
It is currently accepted that the human brain has a limited neurogenic capacity and an impaired regenerative potential. We have previously shown existence of CD271-expressing neural stem cells (NSCs) in subventricular zone (SVZ) Parkinson's disease (PD) patients, which proliferate differentiate towards neurons glial vitro. To study molecular profile these NSCs detail, we performed RNA sequencing mass spectrometry on CD271+ isolated from post-mortem SVZ homogenates SVZ. were through magnetic...
The influence of mechanical stimulation by intermittent compressive force (ICF) physiologic magnitude on osteoclastic bone resorption was investigated in cultures fetal mouse cartilaginous long bones. Exposure to ICF resulted a significant decrease mineral resorption, as indicated the decreased release 45Ca and number osteoclasts diaphysis. Conditioned medium (CM) from ICF-exposed periosteum-free (ICF-CM), but not control (Co-CM), inhibited fresh bones cultured under conditions. Co-CM...
Kinesin family member 21b (kif21b) is one of the few multiple sclerosis (MS) risk genes with a presumed central nervous system function. Kif21b belongs to kinesin family, proteins involved in intracellular transport and organelles. We hypothesised that kif21b neurodegenerative component MS Alzheimer's (AD) disease. Post-mortem expression was assessed 50 MS, 58 age gender matched non-demented controls (NDC) AD. five-fold increased AD compared NDC aged below 62 years (p = 8*10-5), three-fold...
Gliomas are the most common primary brain tumors. Their highly invasive character and heterogeneity of active oncogenic pathways within single tumors complicate development curative therapies cause poor patient prognosis. Glioma cells express intermediate filament protein glial fibrillary acidic (GFAP), level its alternative splice variant GFAP-δ, relative to canonical GFAP-α, is higher in grade IV compared with lower-grade lower malignant glioma. In this study we show that a high GFAP-δ/α...
Abstract Multiple Sclerosis (MS) is a neuroinflammatory disease mainly affecting young adults. A major pathological hallmark of MS the presence demyelinated lesions in central nervous system. In active phase disease, astrocytes become activated, migrate and contribute to local tissue remodeling that ultimately can result an astroglial scar. This process facilitated by extracellular matrix proteins, including fibronectin. Tissue Transglutaminase (TG2) multifunctional enzyme with ubiquitous...
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist immunomodulatory agents aiming reduce rate relapses. However, these are usually insufficient treat disability. A promising perspective for future therapy regeneration lesions with replacement damaged oligodendrocytes or neurons. Therapies targeting enhancement endogenous remyelination, aim promote activation either...
Abstract During normal brain development, axons are myelinated by mature oligodendrocytes (OLGs). Under pathological, demyelinating conditions within the central nervous system (CNS), axonal remyelination is only partially successful because oligodendrocyte precursor cells (OPCs) largely remain in an undifferentiated state resulting a failure to generate myelinating OLGs. Tissue Transglutaminase (TG2) multifunctional enzyme, which amongst other functions, involved cell differentiation....