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Grienberger C.,TU Munich | Grienberger C.,Howard Hughes Medical Institute | Chen X.,TU Munich | Chen X.,Chongqing Medical University | And 2 more authors.
Trends in Neurosciences | Year: 2015

Dendrites are the predominant entry site for excitatory synaptic potentials in most types of central neurons. There is increasing evidence that dendrites are not just passive transmitting devices but play active roles in synaptic integration through linear and non-linear mechanisms. Frequently, excitatory synapses are formed on dendritic spines. In addition to relaying incoming electrical signals, spines can play important roles in modifying these signals through complex biochemical processes and, thereby, determine learning and memory formation. Here, we review recent advances in our understanding of the function of spines and dendrites in central mammalian neurons in vivo by focusing particularly on insights obtained from Ca2+ imaging studies. © 2014 Elsevier Ltd.

Edbauer D.,German Center for Neurodegenerative Diseases | Edbauer D.,Synergy Systems | Edbauer D.,Ludwig Maximilians University of Munich | Haass C.,German Center for Neurodegenerative Diseases | And 2 more authors.
Current Opinion in Neurobiology | Year: 2016

Expansion of a GGGGCC repeat in C9orf72 causes amyotrophic lateral sclerosis, frontotemporal dementia, or a combination of both. Bidirectional repeat transcripts sequester RNA-binding proteins into nuclear RNA foci. The repeat is translated into dipeptide repeat (DPR) proteins that are crucial for repeat-induced toxicity. DPRs inhibit the proteasome and sequester other proteins. These changes are accompanied by widespread brain atrophy and subclinical cognitive impairment before disease onset. Both repeat RNA and DPRs impair nucleocytoplasmic transport and promote TDP-43 mislocalization and aggregation. Thus, repeat RNA and DPRs may gradually trigger TDP-43 pathology and subsequent region-specific neurodegeneration in a cascade similar to amyloid-β peptide in Alzheimer's disease. The key components of the C9orf72 cascade are promising therapeutic targets in different disease stages. © 2015 The Authors.

Jung C.K.E.,German Center for Neurodegenerative Diseases | Jung C.K.E.,Ludwig Maximilians University of Munich | Herms J.,German Center for Neurodegenerative Diseases | Herms J.,Ludwig Maximilians University of Munich | Herms J.,Synergy Systems
Cerebral Cortex | Year: 2014

Sensory experience alters neuronal circuits, which is believed to form the basis for learning and memory. On a microscopic level, structural changes of the neuronal network are prominently observable as experience-dependent addition and removal of cortical dendritic spines. By environmental enrichment, we here applied broad sensory stimulation to mice and followed the consequences to dendritic spines in the somatosensory cortex utilizing in vivo microscopy. Additionally to apical dendrites of layer V neurons, which are typically analyzed in in vivo imaging experiments, we investigated basal dendrites of layer II/III neurons and describe for the first time experience-dependent alterations on this population of dendrites. On both classes of cortical dendrites, enriched environment- induced substantial changes determined by increases in density and turnover of dendritic spines. Previously established spines were lost after enriched stimulation. A fraction of experience- induced gained spines survived for weeks, which might therefore be functionally integrated into the neuronal network. Furthermore, we observed an increased density of spines that appeared only transiently. Together, we speculate that the cognitive benefits seen in environmental-enriched animals might be a consequence of both, a higher connectivity of the neuronal network due to more established synapses and an enhanced flexibility due to more transient spines. © The Author 2012. Published by Oxford University Press. All rights reserved.

Dimou L.,Ludwig Maximilians University of Munich | Dimou L.,Institute for Stem Cell Research | Dimou L.,Synergy Systems | Gotz M.,Ludwig Maximilians University of Munich | And 2 more authors.
Physiological Reviews | Year: 2014

The diverse functions of glial cells prompt the question to which extent specific subtypes may be devoted to a specific function. We discuss this by reviewing one of the most recently discovered roles of glial cells, their function as neural stem cells (NSCs) and progenitor cells. First we give an overview of glial stem and progenitor cells during development; these are the radial glial cells that act as NSCs and other glial progenitors, highlighting the distinction between the lineage of cells in vivo and their potential when exposed to a different environment, e.g., in vitro. We then proceed to the adult stage and discuss the glial cells that continue to act as NSCs across vertebrates and others that are more lineage-restricted, such as the adult NG2-glia, the most frequent progenitor type in the adult mammalian brain, that remain within the oligodendrocyte lineage. Upon certain injury conditions, a distinct subset of quiescent astrocytes reactivates proliferation and a larger potential, clearly demonstrating the concept of heterogeneity with distinct subtypes of, e.g., astrocytes or NG2-glia performing rather different roles after brain injury. These new insights not only highlight the importance of glial cells for brain repair but also their great potential in various aspects of regeneration. © 2014 the American Physiological Society.

Agency: European Commission | Branch: FP7 | Program: BSG-SME | Phase: SME-2011-1 | Award Amount: 1.36M | Year: 2012

Lighting accounts for 30% of all electricity usage in offices, homes, transport systems and retail. It is expected to be revolutionised by the widespread introduction of LED solid state technology. However, LED technology has some major problems to overcome on the delivered efficiency of multi-LED lights, cost, and the quality of the light colour produced. HERCULES will produce solutions for LED lighting for a range of applications. It will build on a successfully demonstrated concept that combines the light from different LED sources to produce near perfect colour rendition at colour temperatures as low as 2500K. HERCULES will provide the normal benefits of LED lighting high electrical energy to light conversion efficiency (reducing energy consumption), instant start-up and efficient dimmability, but will also allow tuneable colour rendering for applications such as food retailing. It is essential that light sources produce high quality colour rendition, which has proved critical to the health and productivity of workers. High efficiency LEDs have very poor colour rendering and current approaches use multiple phosphors on each LED to generate a poor typically blue rich approximation to natural light. These phosphors can seriously reduce the efficiency of the LED, so more LEDs are required to achieve the light ouput. In a compact light source this has the effect of increasing the temperature of the LEDs, which has a very negative feedback as their efficiency decreases rapidly with temperature. The HERCULES solution will overcome this serious limitation. The key developments in this project will be: Characterisation and selection of suitable high efficiency LEDs Novel electronic driver design Optical design for several form factors, especially to de-image LEDs Low cost injection moulding tool making technique for optical finish Precision injection moulding of optical elements Novel luminaire design for indoor/outdoor/specialist applications

Klein R.,Max Planck Institute of Neurobiology | Klein R.,Synergy Systems | Kania A.,Institute Of Recherches Cliniques Of Montreal Ircm | Kania A.,University of Montréal | Kania A.,McGill University
Current Opinion in Neurobiology | Year: 2014

Ephrin ligands and their Eph receptors hold our attention since their link to axon guidance almost twenty years ago. Since then, they have been shown to be critical for short distance cell-cell interactions in the nervous system. The interest in their function has not abated, leading to ever-more sophisticated studies generating as many surprising answers about their function as new questions. We discuss recent insights into their functions in the developing nervous system, including neuronal progenitor sorting, stochastic cell migration, guidance of neuronal growth cones, topographic map formation, as well as synaptic plasticity. © 2014 Elsevier Ltd.

Winklhofer K.F.,Ruhr University Bochum | Winklhofer K.F.,Synergy Systems
Trends in Cell Biology | Year: 2014

Parkin is an E3 ubiquitin ligase associated with autosomal-recessive Parkinsonism. Moreover, parkin inactivation has been found in sporadic Parkinson's disease (PD), suggesting a wider pathogenic impact than initially predicted. Beyond its role in PD, parkin has also been implicated in innate immune responses. Since its discovery, mounting evidence indicates that parkin can mediate degradative as well as nondegradative ubiquitination. Here we review recent insights into the structure of parkin, the mechanism of its E3 ligase activity, and its functional versatility in an attempt to merge controversial aspects into a more comprehensive picture of this multifaceted E3 ubiquitin ligase. © 2014 Elsevier Ltd.

Hipp M.S.,Max Planck Institute of Biochemistry | Hipp M.S.,Synergy Systems | Park S.-H.,Max Planck Institute of Biochemistry | Park S.-H.,Synergy Systems | And 2 more authors.
Trends in Cell Biology | Year: 2014

Cells possess an extensive network of components to safeguard proteome integrity and maintain protein homeostasis (proteostasis). When this proteostasis network (PN) declines in performance, as may be the case during aging, newly synthesized proteins are no longer able to fold efficiently and metastable proteins lose their functionally active conformations, particularly under conditions of cell stress. Apart from loss-of-function effects, a critical consequence of PN deficiency is the accumulation of cytotoxic protein aggregates, which are also associated with many age-dependent neurodegenerative diseases and other medical disorders. Here we discuss recent evidence that the chronic production of aberrantly folded and aggregated proteins in these diseases is harmful by overtaxing PN capacity, setting in motion a vicious cycle of increasing proteome imbalance that eventually leads to PN collapse and cell death. © 2014 Elsevier Ltd.

Wardlaw J.M.,University of Edinburgh | Smith C.,University of Edinburgh | Dichgans M.,Ludwig Maximilians University of Munich | Dichgans M.,German Center for Neurodegenerative Diseases | Dichgans M.,Synergy Systems
The Lancet Neurology | Year: 2013

The term cerebral small vessel disease (SVD) describes a range of neuroimaging, pathological, and associated clinical features. Clinical features range from none, to discrete focal neurological symptoms (eg, stroke), to insidious global neurological dysfunction and dementia. The burden on public health is substantial. The pathogenesis of SVD is largely unknown. Although the pathological processes leading to the arteriolar disease are associated with vascular risk factors and are believed to result from an intrinsic cerebral arteriolar occlusive disease, little is known about how these processes result in brain disease, how SVD lesions contribute to neurological or cognitive symptoms, and the association with risk factors. Pathology often shows end-stage disease, which makes identification of the earliest stages difficult. Neuroimaging provides considerable insights; although the small vessels are not easily seen themselves, the effects of their malfunction on the brain can be tracked with detailed brain imaging. We discuss potential mechanisms, detectable with neuroimaging, that might better fit the available evidence and provide testable hypotheses for future study. © 2013 Elsevier Ltd.

Hemmer B.,TU Munich | Hemmer B.,Synergy Systems | Kerschensteiner M.,Ludwig Maximilians University of Munich | Kerschensteiner M.,Synergy Systems | And 2 more authors.
The Lancet Neurology | Year: 2015

Multiple sclerosis is a chronic disease of the CNS that leads to substantial disability in most patients. The early phase is characterised by relapses and the later phase by progressive disability. Results from immunological, genetic, and histopathological studies and treatment trials have shown that the immune system plays a key part in the disease course. Findings from animal models and immunological studies of patients with multiple sclerosis suggest a change in the involvement of the immune system during disease initiation and progression. These findings suggest that a peripheral immune response targeting the CNS drives the disease process during the early phase, whereas immune reactions within the CNS dominate the progressive phase. These concepts for the differential involvement of immune responses in the early and progressive phase of this disease have important implications for future research in the pathogenesis and treatment of multiple sclerosis. © 2015 Elsevier Ltd.

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