A5044498878- Neurogenesis and neuroplasticity mechanisms
- Hereditary Neurological Disorders
- Nerve injury and regeneration
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA regulation and disease
- MicroRNA in disease regulation
- Growth Hormone and Insulin-like Growth Factors
- Signaling Pathways in Disease
- Neurological diseases and metabolism
- Axon Guidance and Neuronal Signaling
- RNA modifications and cancer
- Neuroscience and Neuropharmacology Research
- Neurogenetic and Muscular Disorders Research
- Metabolism, Diabetes, and Cancer
- Glycosylation and Glycoproteins Research
- Peroxisome Proliferator-Activated Receptors
- Cellular Mechanics and Interactions
- Cerebral Palsy and Movement Disorders
- Metabolism and Genetic Disorders
- Apelin-related biomedical research
- Ubiquitin and proteasome pathways
- Extracellular vesicles in disease
- Alzheimer's disease research and treatments
- RNA Interference and Gene Delivery
Max Planck Institute for Multidisciplinary Sciences
2022-2025
Universitätsklinikum Gießen und Marburg
2025
Giessen School of Theology
2024
University of Göttingen
2024
Max Planck Institute of Experimental Medicine
2013-2022
Nanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103
2016-2018
Max Planck Society
2003-2014
Robert Koch Institute
2013
Goethe University Frankfurt
2013
Walter de Gruyter (Germany)
2013
We have investigated the developmental regulation of rat insulin-like growth factor I (IGF-I) receptor gene in various tissues using a sensitive and specific solution hybridization/RNase protection assay. For this purpose we characterized IGF-I cDNAs that were cloned from simian virus 40-transformed granulosa cell cDNA library. The clone used these studies encoded putative signal peptide first 53 amino acids alpha subunit was approximately 94% homologous to its human counterpart. expression...
The incidence of Alzheimer's disease (AD), the leading cause dementia, increases rapidly with age, but why age constitutes main risk factor is still poorly understood. Brain ageing affects oligodendrocytes and structural integrity myelin sheaths1, latter which associated secondary neuroinflammation2,3. As support axonal energy metabolism neuronal health4-7, we hypothesized that loss could be an upstream for amyloid-β (Aβ) deposition, central neuropathological hallmark AD. Here identify...
The myelin sheath is a multilamellar plasma membrane extension of highly specialized glial cells laid down in regularly spaced segments along axons. Recent studies indicate that metabolically active and capable communicating with the underlying axon. To be functionally connected to neuron, oligodendrocytes maintain non-compacted as cytoplasmic nanochannels. Here, we used high-pressure freezing for electron microscopy study these regions within close their native state. We identified...
The integrity of myelinated axons relies on homeostatic support from oligodendrocytes (OLs). To determine how OLs detect axonal spiking and rapid axon-OL metabolic coupling is regulated in the white matter, we studied activity-dependent calcium (Ca
SUMMARY Myelination facilitates the rapid conduction of action potentials along axons. In central nervous system (CNS), myelinated axons vary over 100-fold in diameter, with speed scaling linearly increasing diameter. Axon diameter and myelination are closely interlinked, axon exerting a strong influence on myelination. Conversely, myelinating Schwann cells peripheral can both positively negatively affect However, whether is regulated by CNS oligodendrocytes less clear. Here, we investigated...
Mice lacking the expression of proteolipid protein (PLP)/DM20 in oligodendrocytes provide a genuine model for spastic paraplegia (SPG-2). Their axons are well myelinated but exhibit impaired axonal transport and progressive degeneration, which is difficult to attribute absence single myelin protein. We hypothesized that secondary molecular changes PLP null contribute loss PLP/DM20-dependent neuroprotection more insight into glia-axonal interactions this disease model. By gel-based proteome...
Although known for almost 80 years, the physiological role of plasmalogens (PLs), major mammalian ether lipids (ELs), is still enigmatic. Humans that lack ELs suffer from rhizomelic chondrodysplasia punctata (RCDP), a peroxisomal disorder usually resulting in death early childhood. In order to learn more about functions ELs, we generated mouse model RCDP by targeted disruption dihydroxyacetonephosphate acyltransferase gene. The mutant mice revealed multiple abnormalities, such as male...
In its severe form, X-linked adrenoleukodystrophy (ALD) is a lethal neurologic disease of children, characterized by progressive cerebral demyelination and adrenal insufficiency. Associated with biochemical defect peroxisomal β-oxidation, very long-chain fatty acids (VLCFA) build up in tissues that have high turnover lipids, such as central nervous system (CNS) white matter, cortex, testis. Whether the abnormal accumulation VLCFA underlying cause or merely an associated marker unknown. ALD...
Peripheral nerve myelin facilitates rapid impulse conduction and normal motor sensory functions. Many aspects of biogenesis, glia–axonal interactions, homeostasis are poorly understood at the molecular level. We therefore hypothesized that only a fraction all relevant proteins has been identified so far. Combining gel-based gel-free proteomic approaches, we 545 in purified mouse sciatic myelin, including 36 previously known constituents. By mass spectrometric quantification, predominant P0,...
Abstract Most axons in the central nervous system (CNS) are surrounded by a multilayered myelin sheath that promotes fast, saltatory conduction of electrical impulses. By insulating axon, also shields axoplasm from extracellular milieu. In CNS, oligodendrocytes provide support for long‐term maintenance myelinated axons, independent sheath. Here, we use electron microscopy and morphometric analyses to examine evolution axonal oligodendroglial changes mice deficient 2′,3′‐cyclic nucleotide...
Neurons extend long axons that require maintenance and are susceptible to degeneration. Long-term integrity of depends on intrinsic mechanisms including axonal transport extrinsic support from adjacent glial cells. The provided by myelinating oligodendrocytes underlying only partly understood. Oligodendrocytes release extracellular vesicles (EVs) with properties exosomes, which upon delivery neurons improve neuronal viability in vitro. Here, we show oligodendroglial exosome secretion is...
Abstract Erythropoietin (EPO), named after its role in hematopoiesis, is also expressed mammalian brain. In clinical settings, recombinant EPO treatment has revealed a remarkable improvement of cognition, but underlying mechanisms have remained obscure. Here, we show with novel line reporter mice that cognitive challenge induces local/endogenous hypoxia hippocampal pyramidal neurons, hence enhancing expression and receptor (EPOR). High-dose administration, amplifying auto/paracrine EPO/EPOR...
Abstract The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment cholesterol in the membrane. However, it unknown how concentrate above level found nonmyelin membranes. Here, we demonstrate critical role for proteolipids accumulation. Mice lacking most abundant protein, proteolipid protein (PLP), are fully myelinated, but PLP‐deficient exhibits reduced content. We therefore hypothesized that “high...
The underlying cellular mechanisms of catatonia, an executive "psychomotor" syndrome that is observed across neuropsychiatric diseases, have remained obscure. In humans and mice, reduced expression the structural myelin protein CNP associated with catatonic signs in age-dependent manner, pointing to involvement myelin-producing oligodendrocytes. Here, we showed cause low-grade inflammation white matter tracts, which marks a final common pathway Cnp-deficient other mutant mice minor...
Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired myelin-related disorders and upon normal aging. However, molecular cause many pathological features, including frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that presence outfoldings correlates with a loss cytoskeletal septins myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels,...
Proteome and transcriptome analyses aim at comprehending the molecular profiles of brain, its cell-types subcellular compartments including myelin. Despite relevance peripheral nervous system for normal sensory motor capabilities, analogous approaches to nerves myelin have fallen behind evolving technical standards. Here we assess proteome by gel-free, label-free mass-spectrometry deep quantitative coverage. Integration with RNA-Sequencing-based developmental mRNA-abundance neuropathy...
Myelin membranes are dominated by lipids while the complexity of their protein composition has long been considered to be low. However, numerous additional myelin proteins have identified since. Here we revisit proteome biochemically purified from brains healthy c56Bl/6N-mice utilizing complementary proteomic approaches for deep qualitative and quantitative coverage. By gel-free, label-free mass spectrometry, most abundant PLP, MBP, CNP, MOG constitute 38, 30, 5, 1% total protein,...
Myelination of axons provides the structural basis for rapid saltatory impulse propagation along vertebrate fiber tracts, a well-established neurophysiological concept. However, myelinating oligodendrocytes and Schwann cells serve additional functions in neuronal energy metabolism that are remarkably similar to those axon-ensheathing glial unmyelinated invertebrates. Here we discuss myelin evolution physiological functions, beginning with role ensheathing glia preventing ephaptic coupling,...
Myelin, the electrically insulating sheath on axons, undergoes dynamic changes over time. However, it is composed of proteins with long lifetimes. This raises question how such a stable structure renewed. Here, we study integrity myelinated tracts after experimentally preventing formation new myelin in CNS adult mice, using an inducible Mbp null allele. Oligodendrocytes survive recombination, continue to express genes, but they fail maintain compacted sheaths. Using 3D electron microscopy...
Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know what extent the protein composition has remained similar. Here, we use quantitative proteomics analyze purified from human white matter and find that relative abundance of structural proteins PLP, MBP, CNP, SEPTIN8 correlates well with C57Bl/6N mice. Conversely, multiple other were identified exclusively or predominantly myelin....