A5084886058- Neuroinflammation and Neurodegeneration Mechanisms
- Adenosine and Purinergic Signaling
- Immune cells in cancer
- Barrier Structure and Function Studies
- Neurological Disease Mechanisms and Treatments
- Immune Response and Inflammation
- Stress Responses and Cortisol
- Neuroscience and Neuropharmacology Research
- Pain Mechanisms and Treatments
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Lipid metabolism and disorders
- Acute Ischemic Stroke Management
- Atherosclerosis and Cardiovascular Diseases
- Lipoproteins and Cardiovascular Health
- Nuclear Receptors and Signaling
- Inflammasome and immune disorders
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Vagus Nerve Stimulation Research
- Apelin-related biomedical research
- Heme Oxygenase-1 and Carbon Monoxide
- Pain Management and Treatment
- Antioxidant Activity and Oxidative Stress
- Diet and metabolism studies
- Heat shock proteins research
HUN-REN Institute of Experimental Medicine
2016-2025
Hungarian Academy of Sciences
2012-2019
Institute of Biochemistry
2012-2018
HUN-REN Szegedi Biológiai Kutatóközpont
2012-2018
University of Szeged
2015
Microglia are the main immune cells in brain and have roles homeostasis neurological diseases. Mechanisms underlying microglia-neuron communication remain elusive. Here, we identified an interaction site between neuronal cell bodies microglial processes mouse human brain. Somatic junctions a specialized nanoarchitecture optimized for purinergic signaling. Activity of mitochondria was linked with junction formation, which induced rapidly response to activation blocked by inhibition P2Y12...
Microglia are the main immune cells of brain and contribute to common diseases. However, it is unclear how microglia influence neuronal activity survival in injured vivo. Here we develop a precisely controlled model injury induced by cerebral ischaemia combined with fast vivo two-photon calcium imaging selective microglial manipulation. We show that elimination leads striking, 60% increase infarct size, which reversed repopulation. Microglia-mediated protection includes reduction excitotoxic...
Intestinal microbiota are critical for health with changes associated diverse human diseases. Research suggests that altered intestinal can profoundly affect brain function. However, whether altering function directly affects the is unknown. Since it currently unclear how injury induces clinical complications such as infections or paralytic ileus, key contributors to prolonged hospitalization and death post-stroke, we tested in mice hypothesis damage induced microbiota. Experimental stroke...
Inflammation that contributes to acute cerebrovascular disease is driven by the proinflammatory cytokine interleukin-1 and known exacerbate resulting injury. The activity of regulated multimolecular protein complexes called inflammasomes. There are multiple potential inflammasomes activated in diverse diseases, yet nature involved brain injury currently unknown. Here, using a rodent model stroke, we show NLRC4 (NLR family, CARD domain containing 4) AIM2 (absent melanoma 2) contribute We also...
Microglia, the main immunocompetent cells of brain, regulate neuronal function, but their contribution to cerebral blood flow (CBF) regulation has remained elusive. Here, we identify microglia as important modulators CBF both under physiological conditions and during hypoperfusion. Microglia establish direct, dynamic purinergic contacts with in neurovascular unit that shape mice humans. Surprisingly, absence or blockade microglial P2Y12 receptor (P2Y12R) substantially impairs coupling mice,...
Neurotropic herpesviruses can establish lifelong infection in humans and contribute to severe diseases including encephalitis neurodegeneration. However, the mechanisms through which brain's immune system recognizes controls viral infections propagating across synaptically linked neuronal circuits have remained unclear. Using a well-established model of alphaherpesvirus that reaches brain exclusively via retrograde transsynaptic spread from periphery, vivo two-photon imaging combined with...
Neuroimmune interactions may contribute to severe pain and regional inflammatory autonomic signs in complex syndrome (CRPS), a posttraumatic disorder. Here, we investigated peripheral central immune mechanisms translational passive transfer trauma mouse model of CRPS. Small plantar skin-muscle incision was performed female C57BL/6 mice treated daily with purified serum immunoglobulin G (IgG) from patients longstanding CRPS or healthy volunteers followed by assessment paw edema, hyperalgesia,...
Hsp27 belongs to the small heat shock protein family, which are ATP-independent chaperones. The most important function of is based on its ability bind non-native proteins and inhibit aggregation incorrectly folded maintaining them in a refolding-competent state. Additionally, it has anti-apoptotic antioxidant activities. To study effect memory synaptic functions, amyloid-β (Aβ) accumulation, neurodegeneration, we generated transgenic mice overexpressing human crossed with APPswe/PS1dE9...
Advanced cancer causes necrosis and releases damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs activate neutrophils, including generation of neutrophil extracellular traps (NETs), which are injurious, thrombogenic, implicated in metastasis. We hypothesised that mitochondrial DNA (mtDNA) ascites from patients with epithelial ovarian (EOC) would correlate worse outcomes.Banked supernatants newly diagnosed advanced EOC were analysed for mtDNA, elastase, activation healthy donor...
The cytokine interleukin-1 (IL-1) is a key contributor to neuroinflammation and brain injury, yet mechanisms by which IL-1 triggers neuronal injury remain unknown. Here we induced conditional deletion of IL-1R1 in endothelial cells, neurons blood cells assess site-specific actions model cerebral ischaemia mice. Tamoxifen treatment floxed (fl/fl) mice crossed with expressing tamoxifen-inducible Cre-recombinase under the Slco1c1 promoter resulted endothelium-specific significant decrease...
The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, main inflammatory cells brain, has remained unclear date. Therefore, we generated a novel transgenic mouse line which microglial was deleted. We show that shapes both baseline and reactive microglia morphology, process recruitment site injury, adaptation changes cellular volume cell-autonomous manner via regulating membrane conductance. In addition, deficiency results...
Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome the acute phase after experimental models. However, clinical trials testing this approach failed to show efficacy patients chronic 3 mo stroke. Here, we identify potential mechanistic reason phenomenon detecting T...
Chronic stress causes several pain conditions including fibromyalgia. Its pathophysiological mechanisms are unknown, and the therapy is unresolved. Since involvement of interleukin-1 (IL-1) has been described in inflammatory but no data available regarding stress-induced pain, we studied its role a chronic restraint (CRS) mouse model. Female male C57Bl/6J wild-type (WT) IL-1αβ-deficient (knock-out: IL-1 KO) mice were exposed to 6 h immobilization/day for 4 weeks. Mechanonociception, cold...
Abstract Acute brain slices represent a workhorse model for studying the central nervous system (CNS) from nanoscale events to complex circuits. While slice preparation inherently involves tissue damage, it is unclear how microglia, main immune cells and damage sensors of CNS react this injury shape neuronal activity ex vivo. To end, we investigated microglial phenotypes contribution network organization functioning in acute slices. We reveal time-dependent phenotype changes influenced by...
Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading poor outcome. Interleukin-1 (IL-1) an important regulator of post-stroke inflammation, blocking its actions beneficial in pre-clinical models safe the clinical setting. However, distinct roles two major IL-1 receptor type 1 agonists, IL-1α IL-1β, specific role ischemic remain largely unknown. Here we show that IL-1β have different spatio-temporal expression profiles after experimental stroke, with...
The purinergic receptor P2Y12 (P2Y12R) is a well-recognized target for anti-thrombotic agents. This also expressed in microglia, the main immune cells of brain, where it modulates microglial activation states and inflammatory responses. To investigate P2Y12R-mediated actions central nervous system (CNS), developing novel brain-penetrant ligands further vitro studies on brain tissues are essential. A radiolabeled, easily accessible tool compound would significantly advance such drug discovery...
Abstract Glucose is a major fuel for the central nervous system and hypoglycemia significant homeostatic stressor, which elicits counterregulatory reactions. Hypothalamic metabolic- stress-related neurons initiate these actions, however recruitment of glia in control such adaptive circuit remain unknown. Groups fed- fasted-, vehicle-injected, fasted + insulin-injected male mice were compared this study. Bolus insulin administration to resulted hypoglycemia, increased...
The apolipoprotein B-100 (ApoB-100) transgenic mouse line is a model of human atherosclerosis. Latest findings suggest the importance ApoB-100 in development neurodegenerative diseases and microvascular/perivascular localization protein was demonstrated cerebral cortex mice. aim study to characterize cultured brain endothelial cells, pericytes glial cells from wild-type mice effect oxidized low-density lipoprotein (oxLDL) on these cells.Morphology isolated brains wild type characterized by...
Objective- Circulating complement factors are activated by tissue damage and contribute to acute brain injury. The deposition of MBL (mannose-binding lectin), one the initiators lectin pathway, on cerebral endothelium ischemia is a major pathogenic event leading molecular mechanisms through which influences outcome after not understood yet. Approach Results- Here we show that MBL-deficient (MBL-/-) mice subjected display better flow recovery less plasma extravasation in than wild-type mice,...
Abstract A wide variety of systemic pathologies, including infectious and autoimmune diseases, are accompanied by joint pain or inflammation, often mediated circulating immune complexes (ICs). How such stimuli access joints trigger inflammation is unclear. Whole-mount synovial imaging revealed PV1 + fenestrated capillaries at the periphery synovium in lining–sublining interface. Circulating ICs extravasated from these capillaries, nociceptor neurons three distinct macrophage subsets formed a...
Inflammation that develops in the brain and peripheral organs after stroke contributes profoundly to poor outcome of patients. However, mechanisms through which inflammation impacts on injury overall are improperly understood, part because earliest inflammatory events not revealed by current imaging tools. Here, we show single-photon emission computed tomography (NanoSPECT/CT Plus) allows visualization blood barrier (BBB) experimental well before changes can be detected with magnetic...
Selective elimination of microglia from the brain was shown to dysregulate neuronal Ca 2+ signaling and reduce incidence spreading depolarization (SD) during cerebral ischemia. However, mechanisms through which interfere with SD remained unexplored. Here, we identify as essential modulators induction evolution in physiologically intact vivo. Confocal- super-resolution microscopy revealed that a series SDs induced rapid morphological changes microglia, facilitated microglial process...
Aims ApoB-100 is the major protein component of cholesterol- and triglyceride-rich LDL VLDL lipoproteins in serum. Previously, we generated partially described transgenic mice overexpressing human protein. Here, further characterize this strain order to reveal a possible link between hypeprlipidemia neurodegeneration. Methods Results We analyzed serum cerebral lipid profiles, tau phosphorylation patterns, amyloid plaque-formation, neuronal apoptosis synaptic plasticity young (3 month old),...