A5021492493- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Parkinson's Disease Mechanisms and Treatments
- Memory and Neural Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Medical Imaging Techniques and Applications
- Advanced MRI Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- Neurogenesis and neuroplasticity mechanisms
- Genetics and Neurodevelopmental Disorders
- RNA regulation and disease
- Nuclear Receptors and Signaling
- Endoplasmic Reticulum Stress and Disease
- Neurological disorders and treatments
- Mitochondrial Function and Pathology
- Herpesvirus Infections and Treatments
- Radiomics and Machine Learning in Medical Imaging
- CAR-T cell therapy research
- Autism Spectrum Disorder Research
- Advanced X-ray and CT Imaging
- Animal Virus Infections Studies
- Diet and metabolism studies
University of Cologne
2024
University of Wisconsin–Madison
2011-2023
University Hospital Heidelberg
2019
Heidelberg University
2019
William S. Middleton Memorial Veterans Hospital
2013
Academic Center for Dentistry Amsterdam
2012
University of Amsterdam
2012
Ruhr University Bochum
2009
University of Florida
2002-2008
University Hospital of Zurich
1998-2007
Recombinant adeno-associated virus 2 (rAAV2) has been shown to deliver genes neurons effectively in the brain, retina, and spinal cord. The characterization of new AAV serotypes revealed that they have different patterns transduction diverse tissues. We investigated tropism frequency central nervous system (CNS) three rAAV vector serotypes. vectors contained AAV2 terminal repeats flanking a green fluorescent protein expression cassette under control synthetic CBA promoter, AAV1, AAV2, or...
Recombinant adeno-associated viral vectors display efficient tropism for transduction of the dopamine neurons substantia nigra. Taking advantage this unique property recombinant vectors, we expressed wild-type and A53T mutated human α-synuclein in nigrostriatal adult rats up to 6 months. Cellular axonal pathology, including α-synuclein-positive cytoplasmic inclusions swollen, dystrophic neurites similar those seen brains from patients with Parkinson's disease, developed progressively over...
Several genes encoding proteins critical to the neuronal phenotype, such as brain type II sodium channel gene, are expressed high levels only in neurons. This cell specificity is due, part, long-term repression nonneural cells mediated by repressor protein REST/NRSF (RE1 silencing transcription factor/neural-restrictive factor). We show here that CoREST, a newly identified human protein, functions corepressor for REST. A single zinc finger motif REST required CoREST interaction. Mutations of...
We used a high-titer recombinant adeno-associated virus (rAAV) vector to express WT or mutant human α-synuclein in the substantia nigra of adult marmosets. The protein was expressed 90–95% all nigral dopamine neurons and distributed by anterograde transport throughout their axonal dendritic projections. transduced developed severe neuronal pathology, including α-synuclein-positive cytoplasmic inclusions granular deposits; swollen, dystrophic, fragmented neuritis; shrunken pyknotic, densely...
The therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) for Parkinson's disease is likely to depend on sustained delivery the appropriate amount target areas. Recombinant adeno-associated viral vectors (rAAVs) expressing GDNF may be a suitable system this purpose. aim study was define level that does not affect function normal dopamine (DA) neurons but provide anatomical and behavioral protection against an intrastriatal 6-hydroxydopamine (6-OHDA) lesion in common...
Epidemiological studies report that 80% of the population maintains antibodies (Ab) to wild-type (wt) adeno-associated virus type 2 (AAV2), with 30% expressing neutralizing Ab (NAb). The blood-brain barrier (BBB) provides limited immune privilege brain parenchyma, and response recombinant AAV (rAAV) administration in a naive animal is minimal. However, central nervous system transduction preimmunized animals remains unstudied. Vector may disrupt BBB sufficiently promote an previously...
Overexpression of human α-synuclein (α-syn) using recombinant adeno-associated viral (rAAV) vectors provides a novel tool to study neurodegenerative processes seen in Parkinson's disease and other synucleinopathies. We used pseudotyped rAAV2/5 vector express wild-type (wt) α-syn, A53T mutated or the green fluorescent protein (GFP) primate ventral midbrain. Twenty-four adult common marmosets (Callithrix jacchus) were followed with regular behavioural tests for 1 year after transduction. α-Syn...
Long Term Potentiation (LTP) is a leading candidate mechanism for learning and memory also thought to play role in the progression of seizures intractable epilepsy. Maintenance LTP requires RNA transcription, protein translation signaling through mammalian Target Rapamycin (mTOR) pathway. In peripheral tissue, energy sensor AMP-activated Protein Kinase (AMPK) negatively regulates mTOR cascade upon glycolytic inhibition cellular stress. We recently demonstrated that inhibitor...
Analysis software for medical image data tends to be expensive and usable only in a restricted environment. Therefore the aim of current project was implement flexible framework processing visualization which is portable among platforms open different formats including DICOM 3.0. The designed as set tools encapsulate specialized functionality. are full stand alone applications, but they also able present co-operating environment within images other information communicated real time....
Intrastriatal delivery of the tyrosine hydroxylase gene by viral vectors is being explored as a tool for local l -dopa in animals with lesions nigrostriatal pathway. The functional effects reported using this approach have been disappointing, probably because striatal levels attained too low. In present study, we defined critical threshold level -dopa, 1.5 pmol/mg tissue, that has to be reached induce any significant effects. Using new generation high-titer recombinant adeno-associated virus...
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability and leading known genetic cause autism. mental retardation protein (FMRP), which absent or expressed at substantially reduced levels in FXS, binds to controls postsynaptic translation amyloid β-protein precursor (AβPP) mRNA. Cleavage AβPP can produce β-amyloid (Aβ), a 39–43 amino acid peptide mis-expressed Alzheimer's disease (AD) Down (DS). Aβ over-expressed brain Fmr1KO mice, suggesting pathogenic role...
Abstract Oxidative metabolism and cerebral blood flow (CBF) are two of the most important measures in neuroimaging. However, results from concurrent imaging with high spatial temporal resolution have never been published. We used flavoprotein autofluorescence (AF) laser speckle (LSI) anaesthetized rat to map oxidative CBF response single vibrissa stimulation. Autofluorescence responses reflecting demonstrated a fast increase delay 0.1 s. The sign‐reversed contrast started rise 0.6 s reached...
Spinal cord injury (SCI) induces a progressive pathophysiology affecting cell survival and neurological integrity via complex evolving molecular cascades whose interrelationships are not fully understood. The present experiments were designed to: (1) determine potential functional interactions within transcriptional expression profiles obtained after clinically relevant SCI (2) test the consistency of transcript in two genetically immunologically diverse rat strains characterized by...