LEF1 supports metastatic brain colonization by regulating glutathione metabolism and increasing ROS resistance in breast cancer.

More than half of all brain metastases show infiltrating rather than displacing growth at the macro-metastasis/organ parenchyma interface (MMPI), a finding associated with shorter survival. The lymphoid enhancer-binding factor-1 (LEF1) is an epithelial-mesenchymal transition (EMT) transcription factor that is commonly overexpressed in brain-colonizing cancer cells. Here, we overexpressed LEF1 in an in vivo breast cancer brain colonization model.

Strategies of locomotion composition.

This review aims to highlight the importance of saccades during locomotion as a strategy to reduce sensory information loss while the subject is moving. Acquiring sensory data from the environment during movement results in a temporal flow of information, as the sensory precept changes with the position of the observer. Accordingly, the movement pattern shapes the sensory flow.

SEAweb: the small RNA Expression Atlas web application.

We present the Small RNA Expression Atlas (SEAweb), a web application that allows for the interactive querying, visualization and analysis of known and novel small RNAs across 10 organisms. It contains sRNA and pathogen expression information for over 4200 published samples with standardized search terms and ontologies. In addition, SEAweb allows for the interactive visualization and re-analysis of 879 differential expression and 514 classification comparisons.

Mapping Cellular Microenvironments: Proximity Labeling and Complexome Profiling (Seventh Symposium of the Göttingen Proteomics Forum).

Mass spectrometry-based proteomics methods are finding increasing use in structural biology research. Beyond simple interaction networks, information about stable protein-protein complexes or spatially proximal proteins helps to elucidate the biological functions of proteins in a wider cellular context. To shed light on new developments in this field, the Göttingen Proteomics Forum organized a one-day symposium focused on complexome profiling and proximity labeling, two emerging technologies that are gaining significant attention in biomolecular research.

Enhanced Actin Dynamics: A Therapeutic Strategy for Axonal Regeneration?

Spinal cord injury causes permanent paralysis due to the inability of neurons in the central nervous system to regenerate transected axons. In this issue of Neuron, Tedeschi et al. (2019) report that axonal regrowth can be stimulated by actin-depolymerizing proteins, at least in mice.

Correction to: Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease.

The original article was published.

Turning to myelin turnover.

Neural plasticity in the adult central nervous system involves the adaptation of myelination, including the formation of novel myelin sheaths by adult-born oligodendrocytes. Yet, mature oligodendrocytes slowly but constantly turn over their pre-existing myelin sheaths, thereby establishing an equilibrium of replenishment and degradation that may also be subject to adaptation with consequences for nerve conduction velocity. In this short review we highlight selected approaches to the normal turnover of adult myelin in vivo, from injecting radioactive precursors of myelin constituents in the 1960s to current strategies involving isotope labeling and tamoxifen-induced gene targeting.

FIB-SEM of mouse nervous tissue: Fast and slow sample preparation.

Focused ion beam-scanning electron microscopy (FIB-SEM) has become a widely used technique in life sciences. To achieve the best data quality, sample preparation is important and has to be adapted to the specimen and the specific application. Here we illustrate three preparation procedures for mouse nervous tissue: First, the use of high-pressure freezing followed by direct imaging of vitrified tissue without any staining in the FIB-SEM under cryo-conditions as direct and fast procedure.

Cytosolic Trapping of a Mitochondrial Heat Shock Protein Is an Early Pathological Event in Synucleinopathies.

Alpha-synuclein (aSyn) accumulates in intracellular inclusions in synucleinopathies, but the molecular mechanisms leading to disease are unclear. We identify the 10 kDa heat shock protein (HSP10) as a mediator of aSyn-induced mitochondrial impairments in striatal synaptosomes. We find an age-associated increase in the cytosolic levels of HSP10, and a concomitant decrease in the mitochondrial levels, in aSyn transgenic mice.

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse.

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes.

In vivo STED microscopy: A roadmap to nanoscale imaging in the living mouse.

Superresolution microscopy techniques are now widely used, but their application in living animals remains a challenging task. The first superresolution imaging in a live vertebrate was demonstrated with STED microscopy in the visual cortex of an anaesthetized mouse. Here, we explain the requirements for a simple but robust in vivo STED microscope as well as the surgical preparation of the cranial window and the mounting of the mouse in detail.

Contrast enhancement for visualizing neuronal cytoarchitecture by propagation-based x-ray phase-contrast tomography.

Knowledge of the three-dimensional (3d) neuronal cytoarchitecture is an important factor in order to understand the connection between tissue structure and function or to visualize pathological changes in neurodegenerative diseases or tumor development. The gold standard in neuropathology is histology, a technique which provides insights into the cellular organization based on sectioning of the sample. Conventional histology, however, misses the complete 3d information as only individual two-dimensional slices through the object are available.

An Autaptic Culture System for Standardized Analyses of iPSC-Derived Human Neurons.

iPSC-derived human neurons are expected to revolutionize studies on brain diseases, but their functional heterogeneity still poses a problem. Key sources of heterogeneity are the different cell culture systems used. We show that an optimized autaptic culture system, with single neurons on astrocyte feeder islands, is well suited to culture, and we analyze human iPSC-derived neurons in a standardized, systematic, and reproducible manner.

Genetically induced brain inflammation by deletion transiently benefits from microglia depletion.

Reduced expression of 2'-3'-cyclic nucleotide 3'-phosphodiesterase () in humans and mice causes white matter inflammation and catatonic signs. These consequences are experimentally alleviated by microglia ablation colony-stimulating factor 1 receptor (CSF1R) inhibition using PLX5622. Here we address for the first time preclinical topics crucial for translation, most importantly ) the comparison of 2 long-term PLX5622 applications (prevention and treatment) 1 treatment alone, ) the correlation of catatonic signs and executive dysfunction, ) the phenotype of leftover microglia evading depletion, and ) the role of intercellular interactions for efficient CSF1R inhibition.

Myelinating Glia-Specific Deletion of Fbxo7 in Mice Triggers Axonal Degeneration in the Central Nervous System Together with Peripheral Neuropathy.

Myelination of axons facilitates the rapid propagation of electrical signals and the long-term integrity of axons. The ubiquitin-proteasome system is essential for proper protein homeostasis, which is particularly crucial for interactions of postmitotic cells. In our study, we examined how the E3 ubiquitin ligase FBXO7-SCF (SKP1, Cul1, F-box protein) expressed in myelinating cells affects the axon-myelin unit.

Myelin in the Central Nervous System: Structure, Function, and Pathology.

Oligodendrocytes generate multiple layers of myelin membrane around axons of the central nervous system to enable fast and efficient nerve conduction. Until recently, saltatory nerve conduction was considered the only purpose of myelin, but it is now clear that myelin has more functions. In fact, myelinating oligodendrocytes are embedded in a vast network of interconnected glial and neuronal cells, and increasing evidence supports an active role of oligodendrocytes within this assembly, for example, by providing metabolic support to neurons, by regulating ion and water homeostasis, and by adapting to activity-dependent neuronal signals.

Wide sensory filters underlie performance in memory-based discrimination and generalization.

The way animals respond to a stimulus depends largely on an internal comparison between the current sensation and the memory of previous stimuli and outcomes. We know little about the accuracy with which the physical properties of the stimuli influence this type of memory-based discriminative decisions. Research has focused largely on discriminations between stimuli presented in quick succession, where animals can make relative inferences (same or different; higher or lower) from trial to trial.

Publisher Correction: NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies.

Michael W. Sereda was incorrectly associated with the Department of Cellular Neurophysiology, Hanover Medical School, Carl-Neuberg-Str. 1, 30625 Hanover, Germany.

Biological Sample Preparation by High-pressure Freezing, Microwave-assisted Contrast Enhancement, and Minimal Resin Embedding for Volume Imaging.

The described sample preparation technique is designed to combine the best quality of ultrastructural preservation with the most suitable contrast for the imaging modality in a focused ion beam scanning electron microscope (FIB-SEM), which is used to obtain stacks of sequential images for 3D reconstruction and modelling. High-pressure freezing (HPF) allows close to native structural preservation, but the subsequent freeze substitution often does not provide sufficient contrast, especially for a bigger specimen, which is needed for high-quality imaging in the SEM required for 3D reconstruction. Therefore, in this protocol, after the freeze substitution, additional contrasting steps are carried out at room temperature.

An emerging role of dysfunctional axon-oligodendrocyte coupling in neurodegenerative diseases.

Myelin is made by highly specialized glial cells and enables fast axonal impulse propagation. Recent studies show that oligodendrocytes in the central nervous system are, in addition to myelination, required for the integrity and survival of axons, independent of the presence or absence of myelin itself. The underlying mechanism of this support is given by glycolytic oligodendrocytes which provide axons with energy-rich metabolites.

NRG1 type I dependent autoparacrine stimulation of Schwann cells in onion bulbs of peripheral neuropathies.

In contrast to acute peripheral nerve injury, the molecular response of Schwann cells in chronic neuropathies remains poorly understood. Onion bulb structures are a pathological hallmark of demyelinating neuropathies, but the nature of these formations is unknown. Here, we show that Schwann cells induce the expression of Neuregulin-1 type I (NRG1-I), a paracrine growth factor, in various chronic demyelinating diseases.