A5008892103- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- RNA regulation and disease
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- RNA and protein synthesis mechanisms
- Hereditary Neurological Disorders
- Neurogenesis and neuroplasticity mechanisms
- CRISPR and Genetic Engineering
- Cannabis and Cannabinoid Research
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced MRI Techniques and Applications
- Neurogenetic and Muscular Disorders Research
- Neurological diseases and metabolism
- Biochemical effects in animals
- Genetics and Neurodevelopmental Disorders
- CAR-T cell therapy research
- Stress Responses and Cortisol
- Hearing, Cochlea, Tinnitus, Genetics
- RNA modifications and cancer
- Microfluidic and Bio-sensing Technologies
Boehringer Ingelheim (Germany)
2022-2025
Boehringer Ingelheim (Australia)
2025
Takeda (Austria)
2020-2025
UNSW Sydney
2015-2024
Neuroscience Research Australia
2016
University Medical Center of the Johannes Gutenberg University Mainz
2010-2015
Johannes Gutenberg University Mainz
2007-2015
University of Auckland
2003-2014
Max Planck Institute of Experimental Medicine
2001-2013
Heidelberg University
1997-2007
Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two membrane proteolipids, PLP DM20, were shown be essential for integrity of myelinated axons. In absence PLP-DM20, mice assembled compact sheaths but subsequently developed widespread swellings degeneration, associated predominantly with small-caliber nerve fibers. Similar absent dysmyelinated shiverer mice, which lack basic protein (MBP), recurred MBP*PLP double mutants. Thus, fiber was probably...
Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also long-term survival of axons. Degeneration axons occurs in several human myelin diseases, however the molecular mechanisms axon-glia communication maintaining axon integrity poorly understood. Here, we describe signal-mediated transfer exosomes from to neurons. These endosome-derived vesicles secreted by carry specific protein RNA cargo. We show that activity-dependent release...
Axonal degeneration contributes to clinical disability in the acquired demyelinating disease multiple sclerosis. occurs during acute attacks, associated with inflammation, and chronic progressive phase of which inflammation is not prominent. To explore importance interactions between oligodendrocytes axons CNS, we analysed brains rodents humans a null mutation gene encoding major CNS myelin protein, proteolipid protein (PLP1, previously PLP). Histological analyses Plp1 mice autopsy material...
Learning to inhibit drug seeking can be an important strategy for inhibiting relapse, and this modeled by extinguishing in response a drug-paired context. Rats were either extinguished or withdrawn without extinction training (abstinence) from cocaine self-administration, measurements of postsynaptic density proteins the core shell subcompartments nucleus accumbens compared with yoked-saline controls. Only rats had elevations PSD-95, Homer1b/c, Narp core, whereas no measured altered...
We report the characterization of a new rapid-onset model Huntington's disease (HD) generated by adeno-associated virus (AAV) vector–mediated gene transfer N-terminal huntingtin (htt) constructs into rat striatum. Expression exon 1 mutant htt containing 70 CAG repeats rapidly led to neuropathological features associated with HD. In addition, we novel data relating neuronal transduction AAV vectors that modulated phenotype observed in this model. Quantitative reverse transcriptase–polymerase...
Abstract Neuronal excitotoxicity induced by aberrant excitation of glutamatergic receptors contributes to brain damage in stroke. Here we show that tau-deficient (tau −/− ) mice are profoundly protected from excitotoxic and neurological deficits following experimental stroke, using a middle cerebral artery occlusion with reperfusion model. Mechanistically, this protection is due site-specific inhibition glutamate-induced Ras/ERK-mediated toxicity accumulation Ras-inhibiting SynGAP1, which...
The glutamate receptor-associated protein Homer2 regulates alcohol-induced neuroplasticity within the nucleus accumbens (NAC), but precise intracellular signaling cascades involved are not known. This study examined role for NAC metabotropic receptor (mGluR)-Homer2-phosphatidylinositol 3-kinase (PI3K) in regulating excessive alcohol consumption context of scheduled high (SHAC) model binge drinking. Repeated bouts drinking ( approximately 1.5 g/kg per 30 min) elevated Homer2a/b expression and...
Neurotrophin gene delivery, achieved by “close-field” electroporation of mesenchymal cells adjacent to the cochlear implant, improved hearing in deafened guinea pigs.
In recent years recombinant adeno-associated viral vectors (AAV) have become increasingly valuable for in vivo studies animals, and are also currently being tested human clinical trials. Wild-type AAV is a non-pathogenic member of the parvoviridae family inherently replication-deficient. The broad transduction profile, low immune response as well strong persistent transgene expression achieved with these has made them popular versatile tool vitro gene delivery. rAAVs can be easily cheaply...
Cannabinoid type 1 (CB1) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system beneficial for treatment obesity related metabolic diseases. The hypothalamus plays critical role in regulating energy balance by modulating both food intake expenditure. Although CB1 signaling has been implicated modulation these mechanisms, complete understanding its still lacking. Here we combined genetic approach with use adeno-associated viral...
Recombinant adeno-associated virus (AAV) vectors are versatile tools for gene transfer to the central nervous system (CNS) and proof-of-concept studies in adult rodents have shown that use of cell type-specific promoters is sufficient target AAV-mediated transgene expression glia. However, neurological disorders caused by glial pathology usually an early onset. Therefore, modelling treatment these conditions require expanding concept targeted promoter selectivity delivery immature CNS. Here,...
Mutations of the proteolipid protein (Plp) gene cause a generalized central nervous system (CNS) myelin deficit in Pelizaeus-Merzbacher disease man and various tremor syndromes animal models. X-linked spastic paraplegia is also due to Plp mutations but has different clinical profile more restricted pathology involving specific tracts regions. We have shown previously that PLP overexpression mice homozygous for transgene results premature arrest CNS myelination death. Here, we demonstrate...
Alcohol increases the expression of Group 1 metabotropic glutamate receptors (mGluRs) and their associated scaffolding protein Homer2 stimulates phosphatidylinositol 3-kinase (PI3K) within nucleus accumbens (NAC). Moreover, functional studies suggest that NAC mGluR/Homer2/PI3K signaling may be a potential target for pharmacotherapeutic intervention in alcoholism.Immunoblotting was conducted to examine effects alcohol consumption under drinking-in-the-dark (DID) procedures on mGluR-associated...
Release of conventional neurotransmitters is mainly controlled by calcium (Ca 2+ ) influx via high-voltage-activated (HVA), Ca v 2, channels (“N-, P/Q-, or R-types”) that are opened action potentials. Regulation transmission subthreshold depolarizations does occur, but there little evidence low-voltage-activated, 3 (“T-type”), take part. GABA release from cortical perisomatic-targeting interneurons affects numerous physiological processes, and yet its underlying control mechanisms not fully...