Patients with brain tumors suffer from intense psychosocial distress. Although the prevalence of depressive symptoms in patients with brain tumors is high, the pharmacological antidepressant treatment of those patients is not well defined and results from clinical trials are largely missing. In this review, we describe the current standard of evidence and clinical guidelines for the pharmacological treatment of depression in brain tumor patients.
View Article and Find Full Text PDFComprehensive analysis of tissue cell type composition using microscopic techniques has primarily been confined to ex vivo approaches. Here, we introduce NuCLear (Nucleus-instructed tissue composition using deep learning), an approach combining in vivo two-photon imaging of histone 2B-eGFP-labeled cell nuclei with subsequent deep learning-based identification of cell types from structural features of the respective cell nuclei. Using NuCLear, we were able to classify almost all cells per imaging volume in the secondary motor cortex of the mouse brain (0.
View Article and Find Full Text PDFWe established a low background, Cre-dependent version of the inducible Tet-On system for fast, cell type-specific transgene expression Coexpression of a constitutive, Cre-dependent fluorescent marker selectively allowed single-cell analyses before and after inducible, Tet-dependent transgene expression. Here, we used this method for precise, acute manipulation of neuronal activity in the living brain. The goal was to study neuronal network homeostasis at cellular resolution.
View Article and Find Full Text PDFBackground: Brain tumors represent a disease that causes both physical and psychological distress for those affected. The pharmacological treatment of depressive symptoms in particular has not been sufficiently researched in these patients. Depression can severely affect the quality of life and has an impact on the course of the disease.
View Article and Find Full Text PDFBackground: A subacute manifestation of muscle weakness in temporal association with a diarrheal intestinal infection is always suspicious of Guillain-Barré syndrome (GBS). GBS is characterized as an acute inflammatory polyneuroradiculopathy, mediated by cross-reacting autoantibodies and typically triggered by various infections, vaccinations or other causes. Hyponatremia can be associated with GBS and is usually seen in more severe cases.
View Article and Find Full Text PDFAlcohol intoxication at early ages is a risk factor for the development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope-labeled mice combined with quantitative mass spectrometry to screen more than 2,000 hippocampal proteins, of which 72 changed synaptic abundance up to twofold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and ankyrin-G.
View Article and Find Full Text PDFVisualization and analysis of axonal organelle transport has been mostly conducted in vitro, using primary neuronal cell cultures, although more recently, intravital organelle imaging has been established in model organisms such as drosophila, zebrafish, and mouse. In this chapter, we describe a method to visualize axonal transport of cellular organelles such as dense core vesicles or mitochondria in the living mouse brain in order to study organelle transport in its native environment. We achieve this goal by injecting adeno-associated viruses expressing fluorescently tagged marker proteins into thalamic nuclei of mice, thereby transducing neurons that project to the surface of the brain.
View Article and Find Full Text PDFMagnetic resonance imaging (MRI) of the brain combined with voxel-based morphometry (VBM) revealed changes in gray matter volume (GMV) in various disorders. However, the cellular basis of GMV changes has remained largely unclear. We correlated changes in GMV with cellular metrics by imaging mice with MRI and two-photon in vivo microscopy at three time points within 12 weeks, taking advantage of age-dependent changes in brain structure.
View Article and Find Full Text PDFA network of communicating tumour cells that is connected by tumour microtubes mediates the progression of incurable gliomas. Moreover, neuronal activity can foster malignant behaviour of glioma cells by non-synaptic paracrine and autocrine mechanisms. Here we report a direct communication channel between neurons and glioma cells in different disease models and human tumours: functional bona fide chemical synapses between presynaptic neurons and postsynaptic glioma cells.
View Article and Find Full Text PDFKey Points: Despite their immense physiological and pathophysiological importance, we know very little about the biology of dense core vesicle (DCV) trafficking in the intact mammalian brain. DCVs are transported at similar average speeds in the anaesthetized and awake mouse brain compared to neurons in culture, yet maximal speed and pausing fraction of transport were higher. Microtubule plus (+)-end extension imaging visualized microtubular growth at 0.
View Article and Find Full Text PDFNeuronal intracellular Cl concentration ([Cl]) influences a wide range of processes such as neuronal inhibition, membrane potential dynamics, intracellular pH (pH) or cell volume. Up to date, neuronal [Cl] has predominantly been studied in model systems of reduced complexity. Here, we implemented the genetically encoded ratiometric Cl indicator Superclomeleon (SCLM) to estimate the steady-state [Cl] in cortical neurons from anesthetized and awake mice using 2-photon microscopy.
View Article and Find Full Text PDFThe lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) has been identified as a receptor for enterovirus 71 uptake and mannose-6-phosphate-independent lysosomal trafficking of the acid hydrolase β-glucocerebrosidase. Here we show that LIMP-2 undergoes proteolytic cleavage mediated by lysosomal cysteine proteases. Heterologous expression and in vitro studies suggest that cathepsin-F is mainly responsible for the lysosomal processing of wild-type LIMP-2.
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