A5078900856- Genomics and Chromatin Dynamics
- Neurotransmitter Receptor Influence on Behavior
- Pluripotent Stem Cells Research
- Neurogenesis and neuroplasticity mechanisms
- Memory and Neural Mechanisms
- RNA Research and Splicing
- Neuroendocrine regulation and behavior
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- CRISPR and Genetic Engineering
- Nerve injury and regeneration
- Cytokine Signaling Pathways and Interactions
- Developmental Biology and Gene Regulation
- Neuropeptides and Animal Physiology
- Neuroscience and Neuropharmacology Research
- Genetic Associations and Epidemiology
- Nuclear Receptors and Signaling
- interferon and immune responses
- Animal Genetics and Reproduction
- Genomic variations and chromosomal abnormalities
- Congenital heart defects research
- Virology and Viral Diseases
- Protein Kinase Regulation and GTPase Signaling
Innsbruck Medical University
2014-2024
Universität Innsbruck
2007-2024
Max Planck Society
2004
Max Planck Institute of Neurobiology
1999-2000
University of Florida
1995-1998
Florida College
1998
Veterinary Medical Teaching Hospital
1995
The three-dimensional (3D) structure of chromatin is intrinsically associated with gene regulation and cell function1-3. Methods based on conformation capture have mapped structures in neuronal systems such as vitro differentiated neurons, neurons isolated through fluorescence-activated sorting from cortical tissues pooled different animals dissociated whole hippocampi4-6. However, changes organization captured by imaging, the relocation Bdnf away nuclear periphery after activation7, are...
ABSTRACT Little is known how social interaction, if offered as an alternative to drug consumption, affects neural circuits involved in reinforcement and substance dependence. Conditioned place preference (CPP) for cocaine (15 mg/kg i.p.) or interaction minutes) stimulus was investigated male Sprague‐Dawley rats. Four episodes with a adult conspecific completely reversed CPP were even able prevent reacquisition of CPP. Social also CPP‐induced expression the immediate‐early gene zif268 nucleus...
The DNA-binding protein SATB2 is genetically linked to human intelligence. We studied its influence on the three-dimensional (3D) epigenome by mapping chromatin interactions and accessibility in control versus SATB2-deficient cortical neurons. find that affects looping between enhancers promoters of neuronal-activity-regulated genes, thus influencing their expression. It also alters A/B compartments, topologically associating domains, frequently interacting regions. Genes SATB2-dependent 3D...
Sex-determination mechanisms in birds and mammals evolved independently for more than 300 million years. Unlike mammals, sex determination operates through a ZZ/ZW chromosome system, which the female is heterogametic sex. However, molecular mechanism remains to be elucidated. Comparative gene mapping revealed that several genes on human 9 (HSA 9) have homologs chicken Z (GGA Z), indicating common ancestry of large parts GGA HSA 9. Based homology maps, we isolated Z-linked ortholog DMRT1, has...
SATB2 is a risk locus for schizophrenia and encodes DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 almost exclusively expressed in pyramidal neurons of two regions important memory formation, cerebral cortex CA1-hippocampal field. Here we show required key hippocampal functions since deletion from mouse forebrain prevents stabilization synaptic long-term potentiation markedly impairs fear object discrimination memory. At molecular level,...
ABSTRACT Rabies virus glycoprotein (RVG) is known to be the only factor that mediates rabies infection. The neurotrophin receptor (p75 NTR ), through its cysteine-rich domain 1, a specific for RVG and neutralizes infectivity, but role in infection has remained obscure. We used adult mouse dorsal root ganglion (DRG) neurons as model study of p75 RV primary neurons. show infects around 20% DRG neurons, which more than 80% are positive, have large diameters, capsaicin insensitive. Surprisingly,...
ORIGINAL RESEARCH article Front. Behav. Neurosci., 24 September 2012Sec. Motivation and Reward Volume 6 - 2012 | https://doi.org/10.3389/fnbeh.2012.00063
Protein-coding genes, guiding differentiation of ES cells into neural cells, have extensively been studied in the past. However, for class ncRNAs only involvement some specific microRNAs (miRNAs) has described. Thus, to characterize entire small non-coding RNA (ncRNA) transcriptome, involved mouse we generated three specialized ribonucleo-protein particle (RNP)-derived cDNA libraries, i.e. from pluripotent progenitors and differentiated respectively. By high-throughput sequencing...
SATB2 is associated with schizophrenia and an important transcription factor regulating neocortical organization circuitry. Rare mutations in cause a syndrome that includes developmental delay, mouse studies identify role for learning memory. Interacting partners BCL11B GATAD2A are also risk genes indicating other interacting or regulated by making contribution to cognition. We used data from Satb2 models generate three gene-sets contain either functionally related targeted at different...
The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms beneficial effect interaction, if offered as mutually exclusive choice to drugs abuse, are under-investigated. rat place preference conditioning (CPP) paradigm, four 15 min episodes with gender- and weight matched male early-adult conspecific inhibited cocaine-induced reinstatement cocaine CPP, model relapse. These protective effects were paralleled reduced...
Abstract Social interaction in an alternative context can be beneficial against drugs of abuse. Stress is known to a risk factor that exacerbate the effects addictive drugs. In this study, we investigated whether positive social are mediated through decrease stress levels. For purpose, rats were trained express cocaine or conditioned place preference (CPP). Behavioural, hormonal, and molecular markers evaluated. We found CPP decreased percentage incorrect transitions grooming corticosterone...
Spinocerebellar ataxia type 6 (SCA6) is an autosomal-dominant neurodegenerative disorder that caused by a CAG trinucleotide repeat expansion in the CACNA1A gene. As one of few bicistronic genes discovered human genome, encodes not only α1A subunit P/Q voltage-gated Ca2+ channel CaV2.1 but also α1ACT protein, 75 kDa transcription factor sharing sequence cytoplasmic C-terminal tail subunit. Isoforms both proteins contain polyglutamine (polyQ) domain expanded SCA6 patients. Although certain...
The induction of lineage-specific gene programs are strongly influenced by alterations in local chromatin architecture. However, key players that impact this genome reorganization remain largely unknown. Here, we report the removal special AT-rich binding protein 2 (SATB2), a nuclear known to bind matrix attachment regions, is event initiating myogenic differentiation. deletion myoblast SATB2 vitro initiates remodeling and accelerates differentiation, which dependent on caspase 7-mediated...
During CNS development, the nuclear protein SATB2 is expressed in superficial cortical layers and determines projection neuron identity. In adult CNS, pyramidal neurons of all a regulator synaptic plasticity long-term memory. Common variation locus confers risk schizophrenia, whereas rare, de novo structural single nucleotide variants cause severe intellectual disability absent or limited speech. To characterize differences molecular function developing vs neocortex, we isolated interactomes...
SATB2 is a schizophrenia risk gene and genetically associated with human intelligence. How it affects cognition at molecular level currently unknown. Here, we show that interactions between SATB2, chromosomal scaffolding protein, the inner nuclear membrane protein LEMD2 orchestrate response of pyramidal neurons to neuronal activation. Exposure novel environment in vivo causes changes shape CA1 hippocampal via SATB2-dependent mechanism. The activity-driven plasticity envelope requires not...
Sympathetic neurons can switch their neurotransmitter phenotype from noradrenergic to cholinergic on exposure neuropoietic cytokines in vitro and vivo . Here, we provide evidence that this transspecification is regulated by the chromatin architecture protein Satb2. Treatment with ciliary neurotrophic factor (CNTF) leukemia inhibitory rapidly strongly increases Satb2 transcript levels cultures of rat superior cervical ganglia neurons. Knockdown endogenous short interfering RNA prevents...
Although the p38 mitogen-activated protein kinases are active in many neuronal populations peripheral and central nervous systems, little is known about physiological functions of postmitotic neurons. We report that activity determines vitro vivo switch from noradrenergic to cholinergic neurotransmission occurs sympathetic neurons on exposure neuropoietic cytokines CNTF LIF. This transdifferentiation serves as a model for plastic mechanisms enable mature change some their without passing...
Neural crest-derived stem cells (NCSCs) from the embryonic peripheral nervous system (PNS) can be reprogrammed in neurosphere (NS) culture to rNCSCs that produce central (CNS) progeny, including myelinating oligodendrocytes. Using global gene expression analysis we now demonstrate completely lose their previous PNS characteristics and acquire identity of neural derived spinal cord. Reprogramming proceeds rapidly results a homogenous population Olig2-, Sox3-, Lex-positive CNS cells. Low-level...
We investigated if counterconditioning with dyadic (i.e., one-to-one) social interaction, a strong inhibitor of the subsequent reacquisition cocaine conditioned place preference (CPP), differentially modulates activity diverse brain regions oriented along mediolateral corridor reaching from interhemispheric sulcus to anterior commissure, i.e., nucleus vertical limb diagonal band, medial septal nucleus, major island Calleja, intermediate part lateral and accumbens shell core. also involvement...
We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported drugs of abuse abnormally activated p38, a member mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed investigate expression form p38 (pp38) accumbens shell and core rats expressing CPP 1 h, 2 h 24 after test. hypothesized will increase pp38 shell/core as compared CPP. Surprisingly,...
Dopaminergic neurons derived from pluripotent stem cells are among the best investigated products of in vitro cell differentiation owing to their potential use for neurorestorative therapy Parkinson's disease. However, classical protocols both mouse and human generate a limited percentage dopaminergic yield considerable cellular heterogeneity comprising numerous scarcely characterized populations. To improve midbrain neurons, we established extensive strictly quantitative gene expression...