A5038795824- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Alzheimer's disease research and treatments
- Phagocytosis and Immune Regulation
- Neurological Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- Neurogenesis and neuroplasticity mechanisms
- Immune Response and Inflammation
- Neuroscience and Neuropharmacology Research
- Immune responses and vaccinations
- Barrier Structure and Function Studies
- Olfactory and Sensory Function Studies
- Adenosine and Purinergic Signaling
- Neonatal and fetal brain pathology
- Gut microbiota and health
- Autophagy in Disease and Therapy
- Inflammation biomarkers and pathways
- S100 Proteins and Annexins
- Single-cell and spatial transcriptomics
- Erythrocyte Function and Pathophysiology
- Histone Deacetylase Inhibitors Research
- Neonatal Health and Biochemistry
- Prion Diseases and Protein Misfolding
- Nerve injury and regeneration
- Cholinesterase and Neurodegenerative Diseases
Hertie Institute for Clinical Brain Research
2015-2024
University of Tübingen
2015-2024
German Center for Neurodegenerative Diseases
2015-2024
Munich Cluster for Systems Neurology
2024
Ludwig-Maximilians-Universität München
2024
University of Cambridge
2007-2014
Abstract Alzheimer’s disease is the most common form of dementia in western world, however there no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating intestinal microbiota a number brain disorders, its impact on not known. To end we sequenced bacterial 16S rRNA from fecal samples Aβ precursor protein (APP) transgenic mouse model found remarkable shift gut as compared to non-transgenic wild-type mice. Subsequently generated...
Abstract It is well-known that dead and dying neurons are quickly removed through phagocytosis by the brain’s macrophages, microglia. Therefore, neuronal loss during brain inflammation has always been assumed to be due of subsequent their apoptotic or necrotic death. However, we report in this article under inflammatory conditions primary rat cultures glia, actively induces Specifically, two bacterial ligands, lipoteichoic acid LPS (agonists glial TLR2 TLR4, respectively), stimulated...
Significance Brain ischemia is a major cause of death and disability worldwide, but the cellular mechanisms delayed neuronal loss brain atrophy after cerebral are poorly understood thus currently untreatable. Surprisingly, we find that ischemia, macrophages phagocytose viable functional neurons, causing motor dysfunction. Our data show impairment can be prevented by blocking specific phagocytic pathways, therefore highlight new therapeutic targets for stroke dementia.
Significance Status epilepticus is a frequent neurological emergency. These unabated seizures reduce quality of life, promote the development epilepsy, and can cause death. Activation microglia, brain’s resident immune cells, an invariable feature seizure activity. However, involvement blood-borne cells in inflammatory reaction after remains unresolved. Here we identify blood cell not normally encountered healthy brain, called monocyte, which invades brain tissue contributes to inflammation....
Summary Microglia cells are essential for brain homeostasis and have roles in neurodegenerative diseases. Aging is the main risk factor most diseases, age‐related changes microglia may contribute to susceptibility of aging dysfunction neurodegeneration. We analyzed morphology dynamic behavior neocortical their physiological environment young adult (3‐month‐old), (11‐ 12‐month‐old), aged (26‐ 27‐month‐old) C57BL/6J‐Iba1‐ eGFP mice using vivo 2‐photon microscopy. Results show that surveying...
Alzheimer disease is characterized by neuronal loss and brain plaques of extracellular amyloid β (Aβ), but the means which Aβ may induce not entirely clear. Although high concentrations (μm) can direct toxicity to neurons, we find that low concentration (nm) through a microglia-mediated mechanism. In mixed neuronal-glial cultures from rat cerebellum, 250 nm Aβ1–42 (added as monomers, oligomers or fibers) induced about 30% neurons between 2 3 days. This occurred without any increase in...
Milk-fat globule EGF factor-8 (MFG-E8, SED1, lactadherin) is known to mediate the phagocytic removal of apoptotic cells by bridging phosphatidylserine (PS)-exposing and vitronectin receptor (VR) on phagocytes. However, we show here that MFG-E8 can phagocytosis viable neurons during neuroinflammation induced lipopolysaccharide (LPS), thereby causing neuronal death. In vitro , inflammatory loss independent pathways, inhibited blocking PS/MFG-E8/VR pathway (by adding PS antibodies, annexin V,...
Microglial phagocytosis of dead or dying neurons can be beneficial by preventing the release damaging and/or pro-inflammatory intracellular components. However, there is now evidence that under certain conditions, such as inflammation, microglia also phagocytose viable neurons, thus executing their death. Such phagocytic cell death may result from exposure phosphatidylserine (PS) other eat-me signals on otherwise a physiological activation sub-toxic insult, and neuronal activated microglia....
Microglia activated through Toll‐like receptor (TLR)‐2 or ‐4 can cause neuronal death by phagocytosing otherwise‐viable neurons—a form of cell called “phagoptosis.” UDP release from neurons has been shown to provoke microglial phagocytosis via P2Y 6 receptors, but whether inhibition this process affects survival is unknown. We tested here signaling could prevent in inflammatory conditions, and induce phagoptosis stressed viable neurons. find that delayed loss mixed neuronal/glial cultures...
Abstract Aggregates of medin amyloid (a fragment the protein MFG-E8, also known as lactadherin) are found in vasculature almost all humans over 50 years age 1,2 , making it most common currently known. We recently reported that aggregates blood vessels ageing wild-type mice, causing cerebrovascular dysfunction 3 . Here we demonstrate amyloid-β precursor (APP) transgenic mice and patients with Alzheimer’s disease co-localizes vascular deposits, deficiency reduces deposition by half. Moreover,...
Immune cells of myeloid lineage are encountered in the Alzheimer’s disease (AD) brain, where they cluster around amyloid-β plaques. However, assigning functional roles to cell subtypes has been problematic, and potential for peripheral alleviate AD pathology remains unclear. Therefore, we asked whether replacement brain-resident with monocytes alters amyloid deposition two mouse models cerebral β-amyloidosis (APP23 APPPS1). Interestingly, early after repopulation, infiltrating neither...
Rotenone, a common pesticide and inhibitor of mitochondrial complex I, induces microglial activation loss dopaminergic neurons in models Parkinson's disease. However, the mechanisms rotenone neurotoxicity are still poorly defined. Here, we used primary neuronal/glial cultures prepared from rat cerebella to investigate contribution microglia neuronal cell death induced by low concentrations rotenone. Rotenone at 2.5 nm over several days without increasing numbers necrotic or apoptotic...
Sepsis-associated encephalopathy (SAE) represents diverse cerebral dysfunctions in response to pathogen-induced systemic inflammation. Peripheral exposure lipopolysaccharide (LPS), a component of the gram-negative bacterial cell wall, has been extensively used model Our previous studies suggested that LPS led hippocampal neuron death and synaptic destruction vivo. However, underlying roles activated microglia these neuronal changes remained unclear. Here, from two different strains...
Microglial research has been constrained by a rolling series of dichotomies such as "resting versus activated" or "M1 M2". This Manichean perspective good bad microglia is in sharp contrast with the wide repertoire microglial functions, exerted from development to aging and diseases, brought light recent years. New designations continuously arising attempt describe different states transcriptomics other readouts may thus easily lead misleading, although unintentional, coupling categories...