A5065549960- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Parkinson's Disease Mechanisms and Treatments
- Ion channel regulation and function
- Mitochondrial Function and Pathology
- Photoreceptor and optogenetics research
- Neurological disorders and treatments
- Immune cells in cancer
- RNA Research and Splicing
- S100 Proteins and Annexins
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Autoimmune Neurological Disorders and Treatments
- Prion Diseases and Protein Misfolding
- Memory and Neural Mechanisms
- Receptor Mechanisms and Signaling
- Neonatal and fetal brain pathology
- Lysosomal Storage Disorders Research
- Retinal Development and Disorders
- Adipose Tissue and Metabolism
- Advanced Fluorescence Microscopy Techniques
Munich Cluster for Systems Neurology
2017-2025
Ludwig-Maximilians-Universität München
2012-2025
Universität Innsbruck
2025
Innsbruck Medical University
2025
University of Cologne
2024
University Hospital Cologne
2023-2024
LMU Klinikum
2020-2022
Urologische Klinik München
2022
Max Planck Institute of Neurobiology
2011-2016
Max Planck Society
2011-2013
Abstract Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation wild-type (WT) neurons, we show that enters WT grafts, and this is accompanied by infiltration. Manipulation function reduced deposition within grafts. Furthermore, vivo imaging identified as carriers pathology previously tissue. Our data thus argue for a hitherto unexplored mechanism propagation.
The bone marrow in the skull is important for shaping immune responses brain and meninges, but its molecular makeup among bones relevance human diseases remain unclear. Here, we show that mouse has most distinct transcriptomic profile compared with other states of health injury, characterized by a late-stage neutrophil phenotype. In humans, proteome analysis reveals distinct, differentially expressed neutrophil-related pathways unique synaptic protein signature. 3D imaging demonstrates...
Numerous loss-of-function mutations in the progranulin ( GRN ) gene cause frontotemporal lobar degeneration with ubiquitin and TAR–DNA binding protein 43-positive inclusions by reduced production secretion of GRN. Consistent observation that has neurotrophic properties, pharmacological stimulation is a promising approach to rescue haploinsufficiency prevent disease progression. We therefore searched for compounds capable selectively increasing levels. Here, we demonstrate four independent...
Huntington's disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies human patients mouse HD models suggest that disturbances neuronal function neocortex play an important role onset progression. However, precise nature time course cortical alterations have remained elusive. Here, we use chronic vivo two-photon calcium imaging to longitudinally monitor activity identified single layer 2/3 primary motor cortex...
Abstract Gene mutations causing cytoplasmic mislocalization of the RNA-binding protein FUS lead to severe forms amyotrophic lateral sclerosis (ALS). Cytoplasmic accumulation is also observed in other diseases, with unknown consequences. Here, we show that drives behavioral abnormalities knock-in mice, including locomotor hyperactivity and alterations social interactions, absence widespread neuronal loss. Mechanistically, identified a progressive increase activity frontal cortex Fus mice...
Anti-NMDA receptor autoantibodies (NMDAR-Abs) in patients with NMDAR encephalitis cause severe disease symptoms resembling psychosis and cognitive dysfunction. After passive transfer of patients' cerebrospinal fluid or human monoclonal anti-GluN1-autoantibodies mice, we find a disrupted excitatory-inhibitory balance resulting from CA1 neuronal hypoexcitability, reduced AMPA (AMPAR) signaling, faster synaptic inhibition acute hippocampal slices. Functional alterations are also reflected...
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease, characterized by the death of upper (UMN) and lower motor neurons (LMN) in cortex, brainstem, spinal cord. Despite decades research, ALS remains incurable, challenging to diagnose, extremely rapid progression. A unifying feature sporadic familial forms cortical hyperexcitability, which precedes symptom onset, negatively correlates with survival, sufficient trigger neurodegeneration rodents. Using...
Excitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption and the storage long-term information, need to be plastic stable at same time. Here, we advanced in vivo STED nanoscopy superresolve distinct features (head size neck length/width) mouse neocortex for up 1 month. While LTP-dependent changes predict highly correlated modifications spine geometry, find both, uncorrelated dynamics, indicating multiple...
Alzheimer's disease (AD) is associated with aberrant neuronal activity, which believed to critically determine symptoms. How these activity alterations emerge, how stable they are over time, and whether cellular dynamics affected by the amyloid plaque pathology remains incompletely understood. We here repeatedly recorded from identified neurons in cortex of awake APPPS1 transgenic mice four weeks during early phase deposition using vivo two-photon calcium imaging. found that this stage...
Article22 April 2022Open Access Source DataTransparent process Astrogenesis in the murine dentate gyrus is a life-long and dynamic Julia Schneider orcid.org/0000-0002-2128-7392 Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany Contribution: Conceptualization, Data curation, Formal analysis, Validation, Investigation, Visualization, Writing - original draft, review & editing Search for more papers by this author Johannes Weigel Investigation...
Toxic proteinaceous deposits and alterations in excitability activity levels characterize vulnerable neuronal populations neurodegenerative diseases. Using vivo two-photon imaging behaving spinocerebellar ataxia type 1 (Sca1) mice, wherein Purkinje neurons (PNs) degenerate, we identify an inhibitory circuit element (molecular layer interneurons [MLINs]) that becomes prematurely hyperexcitable, compromising sensorimotor signals the cerebellum at early stages. Mutant MLINs express abnormally...
Alzheimer's disease (AD) is a protein conformational disorder characterized by two major neuropathological features: extracellular accumulations of amyloid-β peptides in the form plaques and intracellular tangles, consisting hyperphosphorylated tau proteins. Several morphological functional changes are associated with these lesions diseased brain, such as dendritic synaptic alterations, well microglial astroglial recruitment their activation. The availability transgenic mouse models that...
Amyloid-β (Aβ) plaque deposition plays a central role in the pathogenesis of Alzheimer's disease (AD). Post-mortem analysis development mouse models AD revealed that plaques are initially small, but then increase size and become more numerous with age. There is evidence can grow uniformly over time; however, complementary hypothesis small cluster together thereby forming larger plaques. To investigate latter hypothesis, we studied formation APPPS1 mice using vivo two-photon microscopy...
We present evidence, using biochemical and cellular approaches, that the kinase, CK2, negatively controls signaling via Gα s (or olf ) coupled to dopamine D1 adenosine A2A receptors. Pharmacological inhibition of CK2 or knockdown by RNAi lead elevated cAMP levels in receptor-activated neuroblastoma cells. Phosphorylation protein kinase A substrates were increased presence inhibitors mouse striatal slices. The effect receptor agonists on phosphorylation sites was potentiated upon inhibition....
Abstract Considerable fluctuations in cognitive performance and eventual dementia are an important characteristic of alpha-synucleinopathies, such as Parkinson’s disease Lewy Body linked to cortical dysfunction. The presence misfolded aggregated alpha-synuclein the cerebral cortex patients has been suggested play a crucial role this process. However, consequences a-synuclein accumulation on function networks at cellular resolution vivo largely unknown. Here, we induced robust pathology using...
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by the degeneration of cortical and spinal motor neurons. With no effective treatment available to date, patients face progressive paralysis eventually succumb due respiratory failure within only few years. Recent research has revealed multifaceted nature mechanisms cell types involved in neuron degeneration, thereby opening up new therapeutic avenues. Intriguingly, two key features present both ALS rodent models are...