A5036624743- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Stress Responses and Cortisol
- Genetics and Neurodevelopmental Disorders
- Down syndrome and intellectual disability research
- Neuroendocrine regulation and behavior
- Receptor Mechanisms and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Tryptophan and brain disorders
- RNA Research and Splicing
- MicroRNA in disease regulation
- Immune cells in cancer
- Immune Response and Inflammation
- Neurotransmitter Receptor Influence on Behavior
- Frailty in Older Adults
- Lysosomal Storage Disorders Research
- Cell Adhesion Molecules Research
- Circular RNAs in diseases
- Ion channel regulation and function
- Pharmacological Effects and Assays
- Autism Spectrum Disorder Research
- Cellular transport and secretion
- Anesthesia and Neurotoxicity Research
KU Leuven
2016-2025
University of Liverpool
2023
VIB-KU Leuven Center for Brain & Disease Research
2012-2021
Vlaams Instituut voor Biotechnologie
2006-2011
Oklahoma Medical Research Foundation
2011
Novartis (Switzerland)
2006
University of Bristol
2006
University of Houston
2002-2005
Texas Children's Hospital
2004
Baylor College of Medicine
2004
The brain is a site of relative immune privilege. Although CD4 T cells have been reported in the central nervous system, their presence healthy remains controversial, and function largely unknown. We used combination imaging, single cell, surgical approaches to identify CD69+ cell population both mouse human brain, distinct from circulating cells. brain-resident was derived through situ differentiation activated circulatory shaped by self-antigen peripheral microbiome. Single-cell sequencing...
Microglia, the mononuclear phagocytes of central nervous system (CNS), are important for maintenance CNS homeostasis, but also critically contribute to pathology. Here we demonstrate that nuclear factor kappa B (NF-κB) regulatory protein A20 is crucial in regulating microglia activation during homeostasis and In mice, deletion increases microglial cell number affects regulation neuronal synaptic function. Administration a sublethal dose lipopolysaccharide induces massive activation,...
Neural stem cells residing in the hippocampal neurogenic niche sustain lifelong neurogenesis adult brain. Adult (AHN) is functionally linked to mnemonic and cognitive plasticity humans rodents. In Alzheimer's disease (AD), process of generating new neurons at impeded, yet mechanisms involved are unknown. Here we identify miR-132, one most consistently downregulated microRNAs AD, as a potent regulator AHN, exerting cell-autonomous proneurogenic effects neural their progeny. Using distinct AD...
The ability of immune-modulating biologics to prevent and reverse pathology has transformed recent clinical practice. Full utility in the neuroinflammation space, however, requires identification both effective targets for local immune modulation a delivery system capable crossing blood-brain barrier. characterization small population regulatory T (Treg) cells resident brain presents one such potential therapeutic target. Here, we identified interleukin 2 (IL-2) levels as limiting factor...
Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal healthy brain, their involvement hyperactivity AD is unknown. We show increased FC human cingulate cortex several years before amyloid deposition. find same disruption AppNL-F mice. Crucially, these disruptions are accompanied by decreased astrocyte calcium signaling. Recovery astrocytic...
Uptake of l -glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Three (VGLUT1–VGLUT3) are expressed in the mammalian CNS, with partial overlapping expression patterns, and VGLUT2 most abundantly paralog thalamus, midbrain, brainstem. Previous studies have shown that VGLUT1 necessary for glutamatergic transmission hippocampus, but role excitatory unexplored neurons vivo . We examined electrophysiological behavioral consequences loss either one or both...
Copy-number variants of the CYFIP1 gene in humans have been linked to autism spectrum disorders (ASD) and schizophrenia (SCZ), two neuropsychiatric characterized by defects brain connectivity. Here, we show that plays an important role functional connectivity callosal functions. We find Cyfip1-heterozygous mice reduced white matter architecture, similar phenotypes found patients with ASD, SCZ other disorders. Cyfip1-deficient also present decreased myelination axons, altered presynaptic...
Tau is a major driver of neurodegeneration and implicated in over 20 diseases. Tauopathies are characterized by synaptic loss neuroinflammation, but it unclear if these pathological events causally linked. binds to Synaptogyrin-3 on vesicles. Here, we interfered with this function determine the role pathogenic at pre-synaptic terminals. We show that heterozygous knockout synaptogyrin-3 benign mice strongly rescues mutant Tau-induced defects long-term plasticity working memory. It also...
Metabotropic glutamate receptor 7 (mGluR7), a with distinct brain distribution and putative role in anxiety, emotional responding, spatial working memory, could be an interesting therapeutic target for fear anxiety disorders. mGluR7-deficient (mGluR7-/-) mice showed essentially normal performance tests neuromotor exploratory activity passive avoidance learning but prominent anxiolytic behavior two tests. They delayed curve during the acquisition of hidden-platform water maze, three...
The clinical effects of treatment withn β-adrenoceptor (β-AR) agonists and antagonists in heart failure vary with duration therapy, as do the β-AR asthma. Therefore, we hypothesized that chronic “β-blockers” asthma may differ from those observed acutely. We tested this hypothesis an antigen (ovalbumin)-driven murine model Airway resistance responses ( R aw ) to muscarinic agonist methacholine were measured by using forced oscillation technique. In comparison nontreated asthmatic mice, that:...
Vesicular glutamate transporters 1 and 2 (VGLUT1, VGLUT2) show largely complementary distribution in the mature rodent brain tend to segregate synapses with different physiological properties. In hippocampus, VGLUT1 is dominate subtype adult animals, whereas VGLUT2 transiently expressed during early postnatal development. We generated characterized knockout mice order examine functional contribution of this transporter hippocampal synaptic plasticity hippocampus-dependent spatial learning....
Loss of GPR3 reduced amyloid plaque burden and improved cognition in four mouse models Alzheimer’s disease, suggesting that may be a potential therapeutic target.
Germline mutations in SPRED1 , a negative regulator of Ras, have been described neurofibromatosis type 1 (NF1)-like syndrome (NFLS) that included learning difficulties some affected individuals. NFLS belongs to the group phenotypically overlapping neuro-cardio-facial-cutaneous syndromes are all caused by germ line genes Ras/mitogen-activated protein kinase extracellular signal-regulated (ERK) pathway and present with degree or mental retardation. We investigated hippocampus-dependent memory...
Abstract Intracerebral injection of the excitotoxic, endogenous tryptophan metabolite, quinolinic acid (QA), constitutes a chemical model neurodegenerative brain disease. Complementary techniques were combined to examine consequences QA into medial prefrontal cortex (mPFC) C57BL6 mice. In accordance with NMDAR-mediated synapto- and neurotoxic action QA, we found an initial increase in excitability augmentation hippocampal long-term potentiation, converting within two weeks reduction...
Necroptosis is a regulated form of cell death that has been observed in Alzheimer’s disease (AD) along with the classical pathological hallmark lesions amyloid plaques and Tau neurofibrillary tangles. To understand neurodegenerative process AD, we studied role necroptosis mouse models primary neurons. Using immunohistochemistry, demonstrated activated necroptosis-related proteins transgenic mice developing pathology neurons from precursor protein (APP)–Tau double treated phosphorylated seeds...