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Koch J.C.,University of Gottingen | Lingor P.,University of Gottingen | Lingor P.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain
Experimental Eye Research | Year: 2016

Different pathological conditions including glaucoma, optic neuritis, hereditary optic atrophy and traumatic injury lead to a degeneration of retinal ganglion cell axons in the optic nerve. Besides this clinical relevance, several experimental models employ the optic nerve as a model system to examine general mechanisms of axonal degeneration in the central nervous system.Several experimental studies have demonstrated that an activation of autophagy is a prominent feature of axonal degeneration in the optic nerve independent of the underlying pathological condition. However, the function of autophagy in axonal degeneration remains still unclear. Inhibition of autophagy was found to attenuate axonal degeneration within the first hours after optic nerve lesion. Other studies focusing on survival of retinal ganglion cells at later postlesional time points report contradicting results, where both inhibition and induction of autophagy were beneficial for survival, depending on the model system or examination time. Therefore, a more precise understanding of the role and the kinetics of autophagy in axonal degeneration is mandatory to develop new therapies for diseases of the optic nerve.Here, we review the literature on the pathophysiological role of autophagy in axonal degeneration in the optic nerve and discuss its implications for future therapeutic approaches in diseases of the eye and the central nervous system involving axonal degeneration. © 2015 Elsevier Ltd. Source


Wilts B.D.,University of Gottingen | Schaap I.A.T.,University of Gottingen | Schaap I.A.T.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | Schmidt C.F.,University of Gottingen
Biophysical Journal | Year: 2015

Cowpea chlorotic mottle virus (CCMV) forms highly elastic icosahedral protein capsids that undergo a characteristic swelling transition when the pH is raised from 5 to 7. Here, we performed nano-indentation experiments using an atomic force microscope to track capsid swelling and measure the shells' Young's modulus at the same time. When we chelated Ca2+ ions and raised the pH, we observed a gradual swelling of the RNA-filled capsids accompanied by a softening of the shell. Control experiments with empty wild-type virus and a salt-stable mutant revealed that the softening was not strictly coupled to the swelling of the protein shells. Our data suggest that a pH increase and Ca2+ chelation lead primarily to a loosening of contacts within the protein shell, resulting in a softening of the capsid. This appears to render the shell metastable and make swelling possible when repulsive forces among the capsid proteins become large enough, which is known to be followed by capsid disassembly at even higher pH. Thus, softening and swelling are likely to play a role during inoculation. © 2015 Biophysical Society. Source


Snaidero N.,Max Planck Institute for Experimental Medicine | Snaidero N.,University of Gottingen | Mobius W.,Max Planck Institute for Experimental Medicine | Mobius W.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | And 12 more authors.
Cell | Year: 2014

Central nervous system myelin is a multilayered membrane sheath generated by oligodendrocytes for rapid impulse propagation. However, the underlying mechanisms of myelin wrapping have remained unclear. Using an integrative approach of live imaging, electron microscopy, and genetics, we show that new myelin membranes are incorporated adjacent to the axon at the innermost tongue. Simultaneously, newly formed layers extend laterally, ultimately leading to the formation of a set of closely apposed paranodal loops. An elaborated system of cytoplasmic channels within the growing myelin sheath enables membrane trafficking to the leading edge. Most of these channels close with ongoing development but can be reopened in adults by experimentally raising phosphatidylinositol-(3,4,5)-triphosphate levels, which reinitiates myelin growth. Our model can explain assembly of myelin as a multilayered structure, abnormal myelin outfoldings in neurological disease, and plasticity of myelin biogenesis observed in adult life. PaperFlick © 2014 Elsevier Inc. Source


Balasubramanian G.,Max Planck Institute for Biophysical Chemistry | Balasubramanian G.,Center for Nanoscale Microscopy and Molecular Physiology of the Brain | Lazariev A.,Max Planck Institute for Biophysical Chemistry | Arumugam S.R.,Max Planck Institute for Biophysical Chemistry | Duan D.-W.,Max Planck Institute for Biophysical Chemistry
Current Opinion in Chemical Biology | Year: 2014

Nitrogen-Vacancy (NV) color center in diamond is a flourishing research area that, in recent years, has displayed remarkable progress. The system offers great potential for realizing futuristic applications in nanoscience, benefiting a range of fields from bioimaging to quantum-sensing. The ability to image single NV color centers in a nanodiamond and manipulate NV electron spin optically under ambient condition is the main driving force behind developments in nanoscale sensing and novel imaging techniques. In this article we discuss current status on the applications of fluorescent nanodiamonds (FND) for optical super resolution nanoscopy, magneto-optical (spin-assisted) sub-wavelength localization and imaging. We present emerging applications such as single molecule spin imaging, nanoscale imaging of biomagnetic fields, sensing molecular fluctuations and temperatures in live cellular environments. We summarize other current advances and future prospects of NV diamond for imaging and sensing pertaining to bio-medical applications. © 2014 Elsevier Ltd. Source


Cabral-Calderin Y.,University of Gottingen | Cabral-Calderin Y.,Leibniz Institute for Primate Research | Schmidt-Samoa C.,University of Gottingen | Wilke M.,University of Gottingen | And 2 more authors.
Journal of Cognitive Neuroscience | Year: 2015

When our brain is confronted with ambiguous visual stimuli, perception spontaneously alternates between different possible interpretations although the physical stimulus remains the same. Both alpha (8–12 Hz) and gamma (>30 Hz) oscillations have been reported to correlate with such spontaneous perceptual reversals. However, whether these oscillations play a causal role in triggering perceptual switches remains unknown. To address this question, we applied transcranial alternating current stimulation (tACS) over the posterior cortex of healthy human participants to boost alpha and gamma oscillations. At the same time, participants were reporting their percepts of an ambiguous structure-from-motion stimulus. We found that tACS in the gamma band (60 Hz) increased the number of spontaneous perceptual reversals, whereas no significant effect was found for tACS in alpha (10 Hz) and higher gamma (80 Hz) frequencies. Our results suggest a mechanistic role of gamma but not alpha oscillations in the resolution of perceptual ambiguity. © 2015 Massachusetts Institute of Technology. Source

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