TY - JOUR AB - Extracting biological information from awake and unrestrained mice is imperative to in vivo basic and pre-clinical research. Accordingly, imaging methods which preclude invasiveness, anesthesia, and/or physical restraint enable more physiologically relevant biological data extraction by eliminating these extrinsic confounders. In this article, we discuss the recent development of shortwave infrared (SWIR) fluorescent imaging to visualize peripheral organs in freely-behaving mice, as well as propose potential applications of this imaging modality in the neurosciences. AU - Arus, B.A. AU - Cosco, E. AU - Yiu, J. AU - Balba, I. AU - Bischof, T.S. AU - Sletten, E.M.* AU - Bruns, O.T. C1 - 67850 C2 - 54328 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Shortwave infrared fluorescence imaging of peripheral organs in awake and freely moving mice. JO - Front. Neurosci. VL - 17 PB - Frontiers Media Sa PY - 2023 SN - 1662-453X ER - TY - JOUR AB - BackgroundRecent studies have found that troponin T parallels the structural and functional decay of peripheral nerves at the level of the lower limbs in patients with type 2 diabetes (T2D). The aim of this study was to determine whether this finding can also be reproduced at the level of the upper limbs.MethodsTen patients with fasting glucose levels >100 mg/dl (five with prediabetes and five with T2D) underwent magnetic resonance neurography of the right upper arm comprising T2-weighted and diffusion weighted sequences. The fractional anisotropy (FA), an indicator for the structural integrity of peripheral nerves, was calculated in an automated approach for the median, ulnar, and radial nerve. All participants underwent additional clinical, serological, and electrophysiological assessments.ResultsHigh sensitivity Troponin T (hsTNT) and HbA1c were negatively correlated with the average FA of the median, ulnar and radial nerve (r = -0.84; p = 0.002 and r = -0.68; p = 0.032). Both FA and hsTNT further showed correlations with items of the Michigan Hand Outcome Questionnaire (r = -0.76; p = 0.010 and r = 0.87; p = 0.001, respectively). A negative correlation was found for hsTNT and HbA1c with the total Purdue Pegboard Test Score (r = -0.87; p = 0.001 and r = -0.68; p = 0.031).ConclusionThis study is the first to find that hsTNT and HbA1c are associated with functional and structural parameters of the nerves at the level of the upper limbs in patients with impaired glucose tolerance and T2D. Our results support the hypothesis that hyperglycemia-related microangiopathy, represented by elevated hsTNT levels, is a contributor to nerve damage in diabetic polyneuropathy. AU - Jende, J.M.E.* AU - Kender, Z.* AU - Morgenstern, J.* AU - Renn, P.* AU - Mooshage, C.* AU - Juerchott, A.* AU - Kopf, S.* AU - Nawroth, P.P. AU - Bendszus, M.* AU - Kurz, F.T.* C1 - 64296 C2 - 52056 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Fractional anisotropy and troponin T parallel structural nerve damage at the upper extremities in a group of patients with prediabetes and type 2 diabetes - a study using 3T magnetic resonance neurography. JO - Front. Neurosci. VL - 15 PB - Frontiers Media Sa PY - 2022 SN - 1662-453X ER - TY - JOUR AB - Objective: It is controversially discussed in how far smoking contributes to diabetic polyneuropathy (DPN) in type 2 diabetes (T2D). Diffusion-weighted magnetic resonance neurography (MRN) at 3 Tesla has been shown to provide objective values for structural nerve integrity in patients with T2D. The aim of this study was to investigate the contribution of cigarette smoking on structural nerve integrity in T2D. Methods: This cross-sectional prospective cohort study investigated the structural integrity of the sciatic nerve in 10 smokers, 40 never-smokers, and 20 ex-smokers with T2D and 10 healthy control subjects, using diffusion tensor imaging MRN at 3 Tesla and semi-automated nerve fiber tracking. Results were correlated with clinical, electrophysiological, and serological data. Results: The sciatic nerve's fractional anisotropy (FA), a parameter for structural nerve integrity, was significantly lower in smokers with T2D when compared to controls (p = 0.002) and never-smokers (p = 0.015), and lower in ex-smokers when compared to controls (p = 0.015). In addition, sciatic nerve radial diffusivity, a marker of myelin damage, was increased in smokers versus controls and never-smokers (p = 0.048, p = 0.049, respectively). Furthermore, FA in T2D patients was negatively correlated with clinical and electrophysiological markers of DPN. FA also showed negative correlations with the pulse wave velocity, a marker of arterial stiffness and associated microangiopathy, in controls (r = -0.70; p = 0.037), never-smokers (r = -0.45; p = 0.004), ex-smokers (r = -0.55; p = 0.009), and a similar trend in smokers (r = -0.63; p = 0.076). Negative correlations were found between FA and skin auto-fluorescence, a marker of tissue advanced glycation end product accumulation and therefore long-term glycemic stress in T2D, in never-smokers (r = -0.39; p = 0.020) and smokers (r = -0.84; p = 0.004), but not in ex-smokers (r = -0.07; p = 0.765). Conclusion: The findings indicate that smoking contributes to sciatic nerve damage in T2D, potentially worsening DPN due to glycemic stress and less microangiopathy-associated myelin damage in active smokers, while angiopathic effects predominate in ex-smokers. To stop smoking may therefore pose a promising preventive measure to slow the progression of DPN in T2D. AU - Jende, J.M.E.* AU - Mooshage, C.* AU - Kender, Z.* AU - Kopf, S.* AU - Groener, J.B.* AU - Heiland, S.* AU - Juerchott, A.* AU - Nawroth, P.P. AU - Bendszus, M.* AU - Kurz, F.T.* C1 - 64518 C2 - 52247 TI - Magnetic resonance neurography reveals smoking-associated decrease in sciatic nerve structural integrity in Type 2 diabetes. JO - Front. Neurosci. VL - 15 PY - 2022 SN - 1662-453X ER - TY - JOUR AB - A prominent goal of neuroscience is to improve our understanding of how brain structure and activity interact to produce perception, emotion, behavior, and cognition. The brain's network activity is inherently organized in distinct spatiotemporal patterns that span scales from nanometer-sized synapses to meter-long nerve fibers and millisecond intervals between electrical signals to decades of memory storage. There is currently no single imaging method that alone can provide all the relevant information, but intelligent combinations of complementary techniques can be effective. Here, we thus present the latest advances in biomedical and biological engineering on photoacoustic neuroimaging in the context of complementary imaging techniques. A particular focus is placed on recent advances in whole-brain photoacoustic imaging in rodent models and its influential role in bridging the gap between fluorescence microscopy and more non-invasive techniques such as magnetic resonance imaging (MRI). We consider current strategies to address persistent challenges, particularly in developing molecular contrast agents, and conclude with an overview of potential future directions for photoacoustic neuroimaging to provide deeper insights into healthy and pathological brain processes. AU - Bodea, S.V. AU - Westmeyer, G.G. C1 - 62421 C2 - 50841 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Photoacoustic neuroimaging - Perspectives on a maturing imaging technique and its applications in neuroscience. JO - Front. Neurosci. VL - 15 PB - Frontiers Media Sa PY - 2021 SN - 1662-453X ER - TY - JOUR AB - Background: Nerve damage in diabetic neuropathy (DN) is assumed to begin in the distal legs with a subsequent progression to hands and arms at later stages. In contrast, recent studies have found that lower limb nerve lesions in DN predominate at the proximal sciatic nerve and that, in the upper limb, nerve functions can be impaired at early stages of DN. Materials and Methods: In this prospective, single-center cross-sectional study, participants underwent diffusion-weighted 3 Tesla magnetic resonance neurography in order to calculate the sciatic nerve’s fractional anisotropy (FA), a surrogate parameter for structural nerve integrity. Results were correlated with clinical and electrophysiological assessments of the lower limb and an examination of hand function derived from the Purdue Pegboard Test. Results: Overall, 71 patients with diabetes, 11 patients with prediabetes and 25 age-matched control subjects took part in this study. In patients with diabetes, the sciatic nerve’s FA showed positive correlations with tibial and peroneal nerve conduction velocities (r = 0.62; p < 0.001 and r = 0.56; p < 0.001, respectively), and tibial and peroneal nerve compound motor action potentials (r = 0.62; p < 0.001 and r = 0.63; p < 0.001, respectively). Moreover, the sciatic nerve’s FA was correlated with the Pegboard Test results in patients with diabetes (r = 0.52; p < 0.001), prediabetes (r = 0.76; p < 0.001) and in controls (r = 0.79; p = 0.007). Conclusion: This study is the first to show that the sciatic nerve’s FA is a surrogate marker for functional and electrophysiological parameters of both upper and lower limbs in patients with diabetes and prediabetes, suggesting that nerve damage in these patients is not restricted to the level of the symptomatic limbs but rather affects the entire peripheral nervous system. AU - Jende, J.M.E.* AU - Kender, Z.* AU - Mooshage, C.* AU - Groener, J.B.* AU - Alvarez-Ramos, L.* AU - Kollmer, J.* AU - Juerchott, A.* AU - Hahn, A.* AU - Heiland, S.* AU - Nawroth, P.P. AU - Bendszus, M.* AU - Kopf, S.* AU - Kurz, F.T.* C1 - 61663 C2 - 50373 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Diffusion tensor imaging of the sciatic nerve as a surrogate marker for nerve functionality of the upper and lower limb in patients with diabetes and prediabetes. JO - Front. Neurosci. VL - 15 PB - Frontiers Media Sa PY - 2021 SN - 1662-453X ER - TY - JOUR AB - Selenium (Se) is known to contribute to several vital physiological functions in mammals: antioxidant defense, fertility, thyroid hormone metabolism, and immune response. Growing evidence indicates the crucial role of Se and Se-containing selenoproteins in the brain and brain function. As for the other essential trace elements, dietary Se needs to reach effective concentrations in the central nervous system (CNS) to exert its functions. To do so, Se-species have to cross the blood–brain barrier (BBB) and/or blood–cerebrospinal fluid barrier (BCB) of the choroid plexus. The main interface between the general circulation of the body and the CNS is the BBB. Endothelial cells of brain capillaries forming the so-called tight junctions are the primary anatomic units of the BBB, mainly responsible for barrier function. The current review focuses on Se transport to the brain, primarily including selenoprotein P/low-density lipoprotein receptor-related protein 8 (LRP8, also known as apolipoprotein E receptor-2) dependent pathway, and supplementary transport routes of Se into the brain via low molecular weight Se-species. Additionally, the potential role of Se and selenoproteins in the BBB, BCB, and neurovascular unit (NVU) is discussed. Finally, the perspectives regarding investigating the role of Se and selenoproteins in the gut-brain axis are outlined. AU - Solovyev, N.* AU - Drobyshev, E.* AU - Blume, B. AU - Michalke, B. C1 - 61406 C2 - 50144 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Selenium at the neural barriers: A review. JO - Front. Neurosci. VL - 15 PB - Frontiers Media Sa PY - 2021 SN - 1662-453X ER - TY - JOUR AB - Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus.In vivoimaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 +/- 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 +/- 21.86 vs 170.1 +/- 49.22;p= 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r= -0.43; 95%CI = -0.66 to -0.14;p= 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r= -0.40; 95%CI = -0.57 to -0.19;p= 0.006), and LDL cholesterol (r= -0.33; 95%CI = -0.51 to -0.11;p= 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r= 0.80; 95%CI = 0.46 to 0.93;p= 0.005). DRG SI was positively correlated with HbA1c levels (r= 0.30; 95%CI = 0.09 to 0.50;p= 0.03) and the triglyceride/HDL ratio (r= 0.40; 95%CI = 0.19 to 0.57;p= 0.007). In this firstin vivostudy, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN. AU - Jende, J.M.E.* AU - Kender, Z.* AU - Rother, C.* AU - Alvarez-Ramos, L.* AU - Groener, J.B.* AU - Pham, M.* AU - Morgenstern, J.* AU - Oikonomou, D.* AU - Hahn, A.* AU - Juerchott, A.* AU - Kollmer, J.* AU - Heiland, S.* AU - Kopf, S.* AU - Nawroth, P.P. AU - Bendszus, M.* AU - Kurz, F.T.* C1 - 60294 C2 - 49372 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Diabetic polyneuropathy is associated with pathomorphological changes in human dorsal root ganglia: A study using 3T MR neurography. JO - Front. Neurosci. VL - 14 PB - Frontiers Media Sa PY - 2020 SN - 1662-453X ER - TY - JOUR AB - Sensory stimulation is an attractive paradigm for studying brain activity using various optical-, ultrasound- and MRI-based functional neuroimaging methods. Optoacoustics has been recently suggested as a powerful new tool for scalable mapping of multiple hemodynamic parameters with rich contrast and previously unachievable spatio-temporal resolution. Yet, its utility for studying the processing of peripheral inputs at the whole brain level has so far not been quantified. We employed volumetric multi-spectral optoacoustic tomography (vMSOT) to non-invasively monitor the HbO, HbR, and HbT dynamics across the mouse somatosensory cortex evoked by electrical paw stimuli. We show that elevated contralateral activation is preserved in the HbO map (invisible to MRI) under isoflurane anesthesia. Brain activation is shown to be predominantly confined to the somatosensory cortex, with strongest activation in the hindpaw region of the contralateral sensorimotor cortex. Furthermore, vMSOT detected the presence of an initial dip in the contralateral hindpaw region in the delta HbO channel. Sensorimotor cortical activity was identified over all other regions in HbT and HbO but not in HbR. Pearson's correlation mapping enabled localizing the response to the sensorimotor cortex further highlighting the ability of vMSOT to bridge over imaging performance deficiencies of other functional neuroimaging modalities. AU - Mc Larney, B. AU - Hutter, M.A. AU - Degtyaruk, O. AU - Dean-Ben, X.L. AU - Razansky, D. C1 - 59437 C2 - 48812 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Monitoring of stimulus evoked murine somatosensory cortex. hemodynamic activity with volumetric multi-. spectral optoacoustic. tomography. JO - Front. Neurosci. VL - 14 PB - Frontiers Media Sa PY - 2020 SN - 1662-453X ER - TY - JOUR AB - Introduction: Tactile stimulation during a placebo treatment could enhance its credibility and thereby boost positive treatment expectations and the placebo effect. This experimental study aimed to investigate the interplay between tactile stimulation, expectation, and treatment credibility for the placebo effect in nausea. Methods: Ninety healthy participants were exposed to a 20-min vection stimulus on two separate days and were randomly allocated to one of three groups on the second day after the baseline period: Placebo transcutaneous electrical nerve stimulation (TENS) with tactile stimulation (n = 30), placebo TENS without tactile stimulation (n = 30), or no intervention (n = 30). Placebo TENS was performed for 20 min at a dummy acupuncture point on both forearms. Expected and perceived nausea severity and further symptoms of motion sickness were assessed at baseline and during the evaluation period. At the end of the experiment, participants in the placebo groups guessed whether they had received active or placebo treatment. Results: Expected nausea decreased significantly more in the placebo groups as compared to the no treatment control group (interaction day × group, F = 6.60, p = 0.003, partial η2 = 0.20), with equal reductions in the two placebo groups (p = 1.0). Reduced expectation went along with a significant placebo effect on nausea (interaction day × group, F = 22.2, p < 0.001, partial η2 = 0.35) with no difference between the two placebo groups (p = 1.0). Twenty-three out of 29 participants in the tactile placebo group (79%) but only 14 out of 30 participants (47%) in the non-tactile placebo group believed that they had received the active intervention (p = 0.015). Bang’s blinding index (BI) indicated random guessing in the non-tactile placebo group (BI = 0; 95% CI, −0.35 to 0.35) and non-random guessing in the direction of an “opposite guess” in the tactile placebo group (BI = −0.52; 95% CI, −0.81 to −0.22). Conclusion: Tactile stimulation during placebo TENS did not further enhance positive treatment expectations and the placebo effect in nausea but increased the credibility of the intervention. Further trials should investigate the interaction between perceived treatment assignment, expectation, and the placebo effect during the course of a trial. AU - Aichner, S.* AU - Haile, A.* AU - Hoffmann, V.* AU - Olliges, E.* AU - Tschöp, M.H. AU - Meissner, K.* C1 - 57527 C2 - 47831 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - The role of tactile stimulation for expectation, perceived treatment assignment and the placebo effect in an experimental nausea paradigm. JO - Front. Neurosci. VL - 13 PB - Frontiers Media Sa PY - 2019 SN - 1662-453X ER - TY - JOUR AB - Background: The amount of fat in ingested food dictates specific activation patterns in the brain, particularly in homeostatic and reward-related areas. Taste-specific brain activation changes have also been shown and the sensitivity to the oral perception of fat is associated with differential eating behavior and physiological parameters. The association between oral fat sensitivity and neuronal network functions has, however, not yet been defined. Objective: We aimed to investigate the association between fat-dependent neuronal functional connectivity patterns and oral fat sensitivity. Design: To investigate the underlying changes in network dynamics caused by fat intake, we measured resting-state functional connectivity in 11 normal-weight male participants before and after a high- vs. a low-fat meal on two separate study days. Oral fat sensitivity was also measured on both days. We used a high-resolution functional magnetic resonance imaging (MRI) sequence to measure any connectivity changes in networks with the seed in the brainstem (nucleus tractus solitarii, NTS), in homeostatic (hypothalamus) and in reward regions (ventral and dorsal striatum). Seed-based functional connectivity (FC) maps were analyzed using factorial analyses and correlation analyses with oral fat sensitivity were also performed. Results: Regardless of fat content, FC between NTS and reward and gustatory areas was lower after ingestion. Oral fat sensitivity was positively correlated with FC between homeostatic regions and limbic areas in the high-fat condition, but negatively correlated with FC between the dorsal striatum and somatosensory regions in the low-fat condition. Conclusion: Our results show the interaction of oral fat sensitivity with the network based neuronal processing of high- vs. low-fat meals. Variations in neuronal connectivity network patterns might therefore be a possible moderator of the association of oral fat sensitivity and eating behavior. AU - Frank-Podlech, S. AU - Heinze, J.M. AU - Machann, J. AU - Scheffler, K.* AU - Camps, G.* AU - Fritsche, A. AU - Rosenberger, M.* AU - Hinrichs, J.* AU - Veit, R. AU - Preissl, H. C1 - 56627 C2 - 47118 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Functional connectivity within the gustatory network is altered by fat content and oral fat sensitivity - A pilot study. JO - Front. Neurosci. VL - 13 IS - JUL PB - Frontiers Media Sa PY - 2019 SN - 1662-453X ER - TY - JOUR AB - Real-time visualization of large-scale neural dynamics in whole mammalian brains is hindered with existing neuroimaging methods having limited capacity when it comes to imaging large tissue volumes at high speeds. Optoacoustic imaging has been shown to be capable of real-time three-dimensional imaging of multiple cerebral hemodynamic parameters in rodents. However, optoacoustic imaging of calcium activity deep within the mammalian brain is hampered by strong blood absorption in the visible light spectrum as well as a lack of activity labels excitable in the near-infrared window. We have developed and validated an isolated whole mouse brain preparation labeled with genetically encoded calcium indicator GCaMP6f, which can closely resemble in vivo conditions. An optoacoustic imaging system coupled to a superfusion system was further designed and used for rapid volumetric monitoring of stimulus-evoked calcium dynamics in the brain. These new imaging setup and isolated preparation's protocols and characteristics are described here in detail. Our new technique captures calcium fluxes as true three-dimensional information across the entire brain with temporal resolution of 10 ms and spatial resolution of 150 μm, thus enabling large-scale neural recording at penetration depths and spatio-temporal resolution scales not covered with any existing neuroimaging techniques. AU - Gottschalk, S. AU - Degtyaruk, O. AU - Mc Larney, B. AU - Rebling, J. AU - Dean-Ben, X.L. AU - Shoham, S.* AU - Razansky, D. C1 - 56008 C2 - 46703 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Isolated murine brain model for large-scale optoacoustic calcium imaging. JO - Front. Neurosci. VL - 13 PB - Frontiers Media Sa PY - 2019 SN - 1662-453X ER - TY - JOUR AB - These are exciting times for research on adult hippocampal neurogenesis (AHN). Debate and controversy regarding the existence of generation of new neurons in the adult, and even diseased human brain flourishes as articles against and in favor accumulate. Adult neurogenesis in the human brain is a phenomenon that does not share the qualities of quantum mechanics. The scientific community should agree that human AHN exists or does not, but not both at the same time. In this commentary, we discuss the latest research articles about hAHN and what their findings imply for the neurogenesis field. AU - Petrik, D. AU - Encinas, J.M.* C1 - 56867 C2 - 47397 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - Perspective: Of mice and men - How widespread is adult neurogenesis? JO - Front. Neurosci. VL - 13 PB - Frontiers Media Sa PY - 2019 SN - 1662-453X ER - TY - JOUR AB - Magnetic resonance imaging (MRI) provides a unique tool for in vivo visualization and tracking of stem cells in the brain. This is of particular importance when assessing safety of experimental cell treatments in the preclinical or clinical setup. Yet, specific imaging requires an efficient and non-perturbing cellular magnetic labeling which precludes adverse effects of the tag, e.g., the impact of iron-oxide-nanoparticles on the critical differentiation and integration processes of the respective stem cell population investigated. In this study we investigated the effects of very small superparamagnetic iron oxide particle (VSOP) labeling on viability, stemness, and neuronal differentiation potential of primary human adult neural stem cells (haNSCs). Cytoplasmic VSOP incorporation massively reduced the transverse relaxation time T2, an important parameter determining MR contrast. Cells retained cytoplasmic label for at least a month, indicating stable incorporation, a necessity for long-term imaging. Using a clinical 3T MRI, 1 x 10(3) haNSCs were visualized upon injection in a gel phantom, but detection limit was much lower (5 x 10(4) cells) in layer phantoms and using an imaging protocol feasible in a clinical scenario. Transcriptional analysis and fluorescence immunocytochemistry did not reveal a detrimental impact of VSOP labeling on important parameters of cellular physiology with cellular viability, stemness and neuronal differentiation potential remaining unaffected. This represents a pivotal prerequisite with respect to clinical application of this method. AU - Stroh, A.* AU - Kressel, J. AU - Coras, R.* AU - Dreyer, A.Y.* AU - Fröhlich, W.* AU - Förschler, A.* AU - Lobsien, D.* AU - Blümcke, I.* AU - Zoubaa, S.* AU - Schlegel, J.* AU - Zimmer, C.* AU - Boltze, J.* C1 - 57248 C2 - 47662 CY - Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland TI - A safe and effective magnetic labeling protocol for MRI-based tracking of human adult neural stem cells. JO - Front. Neurosci. VL - 13 PB - Frontiers Media Sa PY - 2019 SN - 1662-453X ER - TY - JOUR AB - Although nerve cell death is the hallmark of many neurological diseases, the processes underlying this death are still poorly defined. However, there is a general consensus that neuronal cell death predominantly proceeds by regulated processes. Almost 30 years ago, a cell death pathway eventually named oxytosis was described in neuronal cells that involved glutathione depletion, reactive oxygen species production, lipoxygenase activation, and calcium influx. More recently, a cell death pathway that involved many of the same steps was described in tumor cells and termed ferroptosis due to a dependence on iron. Since then there has been a great deal of discussion in the literature about whether these are two distinct pathways or cell type- and insult-dependent variations on the same pathway. In this review, we compare and contrast in detail the commonalities and distinctions between the two pathways concluding that the molecular pathways involved in the regulation of ferroptosis and oxytosis are highly similar if not identical. Thus, we suggest that oxytosis and ferroptosis should be regarded as two names for the same cell death pathway. In addition, we describe the potential physiological relevance of oxytosis/ferroptosis in multiple neurological diseases. AU - Lewerenz, J.* AU - Ates, G.* AU - Methner, A.* AU - Conrad, M. AU - Maher, P.A.* C1 - 53468 C2 - 44871 TI - Oxytosis/ferroptosis-(Re-) emerging roles for oxidative stress-dependent non-apoptotic cell death in diseases of the central nervous system. . JO - Front. Neurosci. VL - 12 PY - 2018 SN - 1662-453X ER - TY - JOUR AB - The pristine formation of complex organs depends on sharp temporal and spatial control of gene expression. Therefore, epigenetic mechanisms have been frequently attributed a central role in controlling cell fate determination. A prime example for this is the first discovered and still most studied epigenetic mark, DNA methylation, and the development of the most complex mammalian organ, the brain. Recently, the field of epigenetics has advanced significantly: new DNA modifications were discovered, epigenomic profiling became widely accessible, and methods for targeted epigenomic manipulation have been developed. Thus, it is time to challenge established models of epigenetic gene regulation. Here, we review the current state of knowledge about DNA modifications, their epigenomic distribution, and their regulatory role. We will summarize the evidence suggesting they possess crucial roles in neurogenesis and discuss whether this likely includes lineage choice regulation or rather effects on differentiation. Finally, we will attempt an outlook on how questions, which remain unresolved, could be answered soon. AU - Stricker, S.H. AU - Götz, M. C1 - 52953 C2 - 44672 CY - Lausanne TI - DNA-methylation: Master or slave of neural fate decisions? JO - Front. Neurosci. VL - 12 PB - Frontiers Media Sa PY - 2018 SN - 1662-453X ER - TY - JOUR AB - Circadian rhythms are widely known to govern human health and disease, but specific pathogenic mechanisms linking circadian disruption to metabolic diseases are just beginning to come to light. This is thanks in part to the development and application of various "omics"-based tools in biology and medicine. Current high-throughput technologies allow for the simultaneous monitoring of multiple dynamic cellular events over time, ranging from gene expression to metabolite abundance and sub-cellular localization. These fundamental temporal and spatial perspectives have allowed for a more comprehensive understanding of how various dynamic cellular events and biochemical processes are related in health and disease. With advances in technology, metabolomics has become a more routine "omics" approach for studying metabolism, and "circadian metabolomics" (i.e., studying the 24-h metabolome) has recently been undertaken by several groups. To date, circadian metabolomes have been reported for human serum, saliva, breath, and urine, as well as tissues from several species under specific disease or mutagenesis conditions. Importantly, these studies have consistently revealed that 24-h rhythms are prevalent in almost every tissue and metabolic pathway. Furthermore, these circadian rhythms in tissue metabolism are ultimately linked to and directed by internal 24-h biological clocks. In this review, we will attempt to put these data-rich circadian metabolomics experiments into perspective to find out what they can tell us about metabolic health and disease, and what additional biomarker potential they may reveal. AU - Dyar, K.A. AU - Eckel-Mahan, K.L.* C1 - 51603 C2 - 43348 CY - Lausanne TI - Circadian metabolomics in time and space. JO - Front. Neurosci. VL - 11 PB - Frontiers Media Sa PY - 2017 SN - 1662-453X ER - TY - JOUR AB - Peripheral insulin acts on the brain to regulate metabolic functions, in particular decreasing food intake and body weight. This concept has been supported by studies in humans relying on the intranasal route of administration, a method that permits the direct permeation of insulin into the CNS without substantial absorption into the blood stream. We investigated if intranasal insulin administration before nocturnal sleep, a period of reduced metabolic activity and largely absent external stimulation, affects food intake and energy turnover on the subsequent morning. Healthy participants who were either young (16 men and 16 women; mean age ± SEM, 23.68 ± 0.40 years, mean BMI ± SEM, 22.83 ± 0.33 kg/m(2)) or elderly (10 men, 9 women; 70.79 ± 0.81 years, 25.27 ± 0.60 kg/m(2)) were intranasally administered intranasal insulin (160 IU) or placebo before a night of regular sleep that was polysomnographically recorded. Blood was repeatedly sampled for the determination of circulating glucose, insulin, leptin and total ghrelin. In the morning, energy expenditure was assessed via indirect calorimetry and subjects were offered a large standardized breakfast buffet from which they could eat ad libitum. Insulin compared to placebo reduced breakfast size by around 110 kcal (1,054.43 ± 50.91 vs. 1,162.36 ± 64.69 kcal, p = 0.0095), in particular decreasing carbohydrate intake (502.70 ± 25.97 vs. 589.82 ± 35.03 kcal, p = 0.0080). This effect was not dependent on sex or age (all p > 0.11). Sleep architecture, blood glucose and hormonal parameters as well as energy expenditure were not or only marginally affected. Results show that intranasal insulin administered to healthy young and elderly humans before sleep exerts a delayed inhibitory effect on energy intake that is not compensated for by changes in energy expenditure. While the exact underlying mechanisms cannot be derived from our data, findings indicate a long-lasting catabolic effect of central nervous insulin delivery that extends across sleep and might be of particular relevance for potential therapeutic applications. AU - Santiago, J.C. AU - Hallschmid, M. C1 - 50640 C2 - 42535 CY - Lausanne TI - Central nervous insulin administration before nocturnal sleep decreases breakfast intake in healthy young and elderly subjects. JO - Front. Neurosci. VL - 11 PB - Frontiers Media Sa PY - 2017 SN - 1662-453X ER - TY - JOUR AB - During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development. AU - Johansson, P.A. C1 - 42746 C2 - 35276 TI - The choroid plexuses and their impact on developmental neurogenesis. JO - Front. Neurosci. VL - 8 PY - 2014 SN - 1662-453X ER - TY - JOUR AB - Careful examination of relevant literature shows that many of the most cherished concepts of the blood-brain barrier are incorrect. These include an almost mythological belief in its immaturity that is unfortunately often equated with absence or at least leakiness in the embryo and fetus. The original concept of a blood-brain barrier is often attributed to Ehrlich; however, he did not accept that permeability of cerebral vessels was different from other organs. Goldmann is often credited with the first experiments showing dye (trypan blue) exclusion from the brain when injected systemically, but not when injected directly into it. Rarely cited are earlier experiments of Bouffard and of Franke who showed methylene blue and trypan red stained all tissues except the brain. The term "blood-brain barrier" "Blut-Hirnschranke" is often attributed to Lewandowsky, but it does not appear in his papers. The first person to use this term seems to be Stern in the early 1920s. Studies in embryos by Stern and colleagues, Weed and Wislocki showed results similar to those in adult animals. These were well-conducted experiments made a century ago, thus the persistence of a belief in barrier immaturity is puzzling. As discussed in this review, evidence for this belief, is of poor experimental quality, often misinterpreted and often not properly cited. The functional state of blood-brain barrier mechanisms in the fetus is an important biological phenomenon with implications for normal brain development. It is also important for clinicians to have proper evidence on which to advise pregnant women who may need to take medications for serious medical conditions. Beliefs in immaturity of the blood-brain barrier have held the field back for decades. Their history illustrates the importance of taking account of all the evidence and assessing its quality, rather than selecting papers that supports a preconceived notion or intuitive belief. This review attempts to right the wrongs. Based on careful translation of original papers, some published a century ago, as well as providing discussion of studies claiming to show barrier immaturity, we hope that readers will have evidence on which to base their own conclusions. AU - Saunders, N.R.* AU - Dreifuss, J.* AU - Dziegielewska, K.M.* AU - Johansson, P.A. AU - Habgood, M.D.* AU - Møllgård, K.* AU - Bauer, H.* C1 - 43064 C2 - 35997 TI - The rights and wrongs of blood-brain barrier permeability studies: A walk through 100 years of history. JO - Front. Neurosci. VL - 8 PY - 2014 SN - 1662-453X ER -