A5101547186- Neuroscience and Neuropharmacology Research
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroendocrine regulation and behavior
- Retinal Development and Disorders
- Neuroscience and Neural Engineering
- Axon Guidance and Neuronal Signaling
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Adipose Tissue and Metabolism
- Memory and Neural Mechanisms
- Botulinum Toxin and Related Neurological Disorders
- Parkinson's Disease Mechanisms and Treatments
- Tryptophan and brain disorders
- MicroRNA in disease regulation
- Mitochondrial Function and Pathology
- Regulation of Appetite and Obesity
- Alzheimer's disease research and treatments
- Histone Deacetylase Inhibitors Research
- Biochemical effects in animals
- Extracellular vesicles in disease
- Neurogenesis and neuroplasticity mechanisms
- Molecular Communication and Nanonetworks
University of Louisville
2025
German Center for Neurodegenerative Diseases
2020-2023
Charité - Universitätsmedizin Berlin
2020-2023
European Neuroscience Institute Göttingen
2011-2019
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2018
Howard Hughes Medical Institute
2006-2013
University of Wisconsin–Madison
2005-2013
University of California, Berkeley
2003-2010
RELX Group (United Kingdom)
2006
The University of Texas Health Science Center at Houston
2006
How the widely used botulinum neurotoxin A (BoNT/A) recognizes and enters neurons is poorly understood. We found that BoNT/A by binding to synaptic vesicle protein SV2 (isoforms A, B, C). Fragments of harbor toxin interaction domain inhibited from neurons. SV2A SV2B knockout hippocampal was abolished restored expressing SV2A, SV2B, or SV2C. Reduction expression in PC12 Neuro-2a cells also entry BoNT/A, which could be isoforms. Finally, mice lacked an isoform (SV2B) displayed reduced...
Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer's disease (AD). Effective therapies these lacking. Here, we evaluated mouse models of age-associated memory impairment deposition to study transcriptome cell type–specific epigenome plasticity in the brain peripheral organs. We determined that aging pathology associated with inflammation impaired synaptic function hippocampal CA1 region result epigenetic-dependent alterations gene expression....
Forgetting is important. Without it, the relative importance of acquired memories in a changing environment lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes response stimulation. receptor internalization, long-term depression (LTD), decay potentiation (LTP) strength required calcium-sensing by Syt3 were abolished through knockout. In spatial memory tasks, mice which was knocked out learned...
Alpha-synuclein (aSyn) plays a crucial role in Parkinson's disease (PD) and other synucleinopathies, since it misfolds accumulates typical proteinaceous inclusions. While the function of aSyn is thought to be related vesicle binding trafficking, precise molecular mechanisms linking with synucleinopathies are still obscure. can spread prion-like manner between interconnected neurons, contributing propagation pathology progressive nature synucleinopathies. Here, we investigated interaction...
Synaptotagmin-I (syt-I) is required for rapid neurotransmitter release in mouse hippocampal neurons. However, contradictory results have been reported regarding evoked and spontaneous secretion from syt-I knock-out (KO) Here, we compared synaptic transmission two different neuron preparations: autaptic cultures which a single isolated cell innervates itself, dissociated mass individual cells are innervated by neighboring cells. In cultures, the total extent of release, size readily...
The synaptotagmins (syts) are a family of molecules that regulate membrane fusion. There 17 mammalian syt isoforms, most which expressed in the brain. However, little is known regarding subcellular location and function majority these syts neurons, largely due to lack isoform-specific antibodies. Here we generated pHluorin-syt constructs harboring luminal domain pH sensor, reports localization, organelles targeted, kinetics sites exocytosis endocytosis. Of interest, only syt-1 2 targeted...
Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone discussed as a novel approach treat dementia. The landscape shaped by chromatin writer eraser proteins, while readers link state cellular function. Chromatin emerged drug targets in cancer research but little known about manipulation adult brain. Here we tested effect JQ1-a small-molecule inhibitor BRD2, BRD3, BRD4 BRDT-on brain function...
1. An improved procedure for the isolation of neurosecretory granules from posterior lobe bovine pituitary gland is described. 2. Of total oxytocic and pressor activities present in original tissue 80% was sedimentable. 3. The were separated mitochondria by prolonged centrifugation a sucrose density gradient. During sedimentation period 5hr. moved progressively into denser regions gradient remained at top. 4. biological measured: activity 11·56±1·63 15·60±3·91 units/mg. protein. 5. A protein...
Delivery of neurotrophins and neuropeptides via long-range trafficking dense core vesicles (DCVs) from the cell soma to nerve terminals is essential for synapse modulation circuit function. But mechanism by which transiting DCVs are captured at specific sites unknown. Here, we discovered that Synaptotagmin-4 (Syt4) regulates capture spatial distribution in hippocampal neurons. We found highly mobile undergo translocation but switch directions only distal ends axons, revealing a circular...
TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, has been extensively studied in nociception of sensory neurons. However, the location function hippocampus debated. We found that expressed oriens-lacunosum-moleculare (OLM) interneurons hippocampus, promotes excitatory innervation. knockout mice have reduced glutamatergic innervation OLM When recruits more glutamatergic, but not GABAergic, terminals to neurons vitro. blocked, input dramatically reduced....
BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation, phenomenon that underlies learning memory. However, whether acts diffuse manner or targeted to specific neuronal subcompartments sites affect circuit function remains unknown. Here, using photoactivation syt-IV (a regulator exocytosis present on BDNF-containing vesicles) transfected rat hippocampal neurons, we discovered distinct subsets vesicles are axons versus dendrites not...
Dendritic spines compartmentalize information in the brain, and their morphological characteristics are thought to underly synaptic plasticity. Here we identify copine-6 as a novel modulator of dendritic spine morphology. We found that brain-derived neurotrophic factor (BDNF) - molecule essential for long-term potentiation strength upregulated recruited hippocampal neurons. Overexpression increased mushroom number decreased filopodia number, while knockdown had opposite effect dramatically...
Interactions between astrocytes and neurons rely on the release uptake of glial neuronal molecules. But whether astrocytic vesicles exist exocytose in a regulated or constitutive fashion is under debate. The majority studies have relied indirect methods astrocyte cultures that do not resemble stellate found vivo. Here, to investigate vesicle-associated proteins exocytosis specifically, we developed simple, fast, economical method for growing monocultures. This superior other monocultures...
Introduction: Recent studies have discovered that lung cancer subtypes possess distinct microbiome profiles within their tumor microenvironment. Additionally, the tumor-associated exhibits altered bacterial pathways, suggesting certain families are more capable of facilitating progression than others. We hypothesize there exists a crosstalk between adenocarcinoma (LUAD) cells and cells. Methods Materials: RNA sequencing (RNA-seq) was performed on LUAD cell lines to explore paracrine...
Neuroligins (NLGs) and Neurexins (NRXs) are important adhesion molecules that promote synapse formation. Multiple splice variants of NLG NRX exist, but their specific functions unclear. Here we report a surrogate postsynaptic cell expressing full-length NLG-1 triggers slow presynaptic differentiation in contacting axon. In contrast, version NLG-1, which lacks insert B (NLG-1ΔB), induces rapid differentiation, reaching the rate seen at native neuronal synapses. We show this acceleration is...