PubMed | Brain and Behavior Discovery Institute and, Tampere University of Technology, University of Helsinki, Brain And Behavior Discovery Institute And Skirov13@Gmailcom and 2 more.
Type: Journal Article | Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2017
Mitochondria play a variety of functional roles in cortical neurons, from metabolic support and neuroprotection to the release of cytokines that trigger apoptosis. In dendrites, mitochondrial structure is closely linked to their function, and fragmentation (fission) of the normally elongated mitochondria indicates loss of their function under pathological conditions, such as stroke and brain trauma. Using in vivo two-photon microscopy in mouse brain, we quantified mitochondrial fragmentation in a full spectrum of cortical injuries, ranging from severe to mild. Severe global ischemic injury was induced by bilateral common carotid artery occlusion, whereas severe focal stroke injury was induced by Rose Bengal photosensitization. The moderate and mild traumatic injury was inflicted by focal laser lesion and by mild photo-damage, respectively. Dendritic and mitochondrial structural changes were tracked longitudinally using transgenic mice expressing fluorescent proteins localized either in cytosol or in mitochondrial matrix. In response to severe injury, mitochondrial fragmentation developed in parallel with dendritic damage signified by dendritic beading. Reconstruction from serial section electron microscopy confirmed mitochondrial fragmentation. Unlike dendritic beading, fragmentation spread beyond the injury core in focal stroke and focal laser lesion models. In moderate and mild injury, mitochondrial fragmentation was reversible with full recovery of structural integrity after 1-2 weeks. The transient fragmentation observed in the mild photo-damage model was associated with changes in dendritic spine density without any signs of dendritic damage. Our findings indicate that alterations in neuronal mitochondria structure are very sensitive to the tissue damage and can be reversible in ischemic and traumatic injuries.During ischemic stroke or brain trauma, mitochondria can either protect neurons by supplying ATP and adsorbing excessive Ca
Neurotar | Date: 2014-04-02
A mobile platform arrangement 10, comprising a first platform 21, referred as a mobile platform and a second platform 11 referred as a support platform, is provided. Both platforms are realized as flat-bottomed members, wherein the support platform is preferably, but not exclusively, provided with sidewalls and wherein a diameter of the support platform 11 exceeds an outer diameter of the mobile platform 21 at least twice. The mobile platform 21 is advantageously positioned onto and/or within the support platform 11. The top surface of the support platform 11 is provided with a friction reducing surface structure 12. The mobile platform 21 is therefore adjusted to perform gliding motion along and/or over the friction reducing surface 12, wherein acceleration necessary for performing gliding motion is imposed to the mobile platform 21 by an external force, provided by movement of an experimental animal within the mobile platform 21. The mobile platform arrangement 10 in addition may comprise means for securing a conscious wake and able to move experimental animal, which means comprise a head adapter and mounting means for head adapter.
PubMed | Eli Lilly and Company, Noxxon Pharma and Neurotar
Type: Comparative Study | Journal: British journal of pharmacology | Year: 2015
Calcitonin gene-related peptide (CGRP) plays an important role in the pathology of migraine, and recent clinical trials suggest the inhibition of CGRP-mediated processes as a new therapeutic option in migraine. In this study, we describe the generation of NOX-L41, a CGRP-neutralizing mirror-image (L-)aptamer (Spiegelmer) and investigate its in vitro and in vivo function.A CGRP-binding Spiegelmer was identified by in vitro selection. Binding studies were performed using surface plasmon resonance (SPR), and the inhibitory activity was determined in cell-based assays. The pharmacokinetic profile comparing i.v. and s.c. dosing was analysed in rats. Intravital two-photon microscopy was employed to follow extravasation from meningeal vessels. Finally, in vivo efficacy was tested in a model of electrically evoked meningeal plasma protein extravasation (PPE) in rats.We identified NOX-L41, a novel CGRP-neutralizing Spiegelmer. SPR studies showed that NOX-L41 binds to human and rat/mouse CGRP with sub-nanomolar affinities and is highly selective against related peptides such as amylin. In vitro, NOX-L41 effectively inhibited CGRP-induced cAMP formation in SK-N-MC cells. In rats, NOX-L41 had a plasma half-life of 8 h. Pharmacodynamic studies showed that NOX-L41 extravasates from blood vessels in the dura mater and inhibits neurogenic meningeal PPE for at least 18 h after single dosing.This is the first description of the CGRP-neutralizing Spiegelmer NOX-L41. Preclinical studies confirmed a role for CGRP in neurogenic PPE and provided proof-of-concept for the potential use of this new drug candidate for the treatment or prevention of migraine.
Neurotar | Date: 2015-09-03
PubMed | Tampere University of Technology, University of Helsinki and Neurotar
Type: Evaluation Studies | Journal: Journal of microscopy | Year: 2016
The morphology of mitochondria can inform about their functional state and, thus, about cell vitality. For example, fragmentation of the mitochondrial network is associated with many diseases. Recent advances in neuronal imaging have enabled the observation of mitochondria in live brains for long periods of time, enabling the study of their dynamics in animal models of diseases. To aid these studies, we developed an automatic method, based on supervised learning, for quantifying the degree of mitochondrial fragmentation in tissue images acquired via two-photon microscopy from transgenic mice, which exclusively express Enhanced cyan fluorescent protein (ECFP) under Thy1 promoter, targeted to the mitochondrial matrix in subpopulations of neurons. We tested the method on images prior to and after cardiac arrest, and found it to be sensitive to significant changes in mitochondrial morphology because of the arrest. We conclude that the method is useful in detecting morphological abnormalities in mitochondria and, likely, in other subcellular structures as well.
Neurotar | Date: 2016-05-17
Optical inspection apparatus and devices, namely, medical imaging apparatus for small animals, in a research laboratory environment. Scientific and technological services, namely, scientific research and testing in the field of brain diseases; research in the field of brain diseases; design of imaging devices and apparatus for medical and diagnostic use in the field of brain research.
Neurotar | Date: 2014-08-15
PubMed | University of Eastern Finland, University of Helsinki and Neurotar
Type: | Journal: Journal of visualized experiments : JoVE | Year: 2014
It is widely acknowledged that the use of general anesthetics can undermine the relevance of electrophysiological or microscopical data obtained from a living animals brain. Moreover, the lengthy recovery from anesthesia limits the frequency of repeated recording/imaging episodes in longitudinal studies. Hence, new methods that would allow stable recordings from non-anesthetized behaving mice are expected to advance the fields of cellular and cognitive neurosciences. Existing solutions range from mere physical restraint to more sophisticated approaches, such as linear and spherical treadmills used in combination with computer-generated virtual reality. Here, a novel method is described where a head-fixed mouse can move around an air-lifted mobile homecage and explore its environment under stress-free conditions. This method allows researchers to perform behavioral tests (e.g., learning, habituation or novel object recognition) simultaneously with two-photon microscopic imaging and/or patch-clamp recordings, all combined in a single experiment. This video-article describes the use of the awake animal head fixation device (mobile homecage), demonstrates the procedures of animal habituation, and exemplifies a number of possible applications of the method.
News Article | April 12, 2016
Prior Scientific reports that its collaboration with Neurotar (Helsinki, Finland) has produced a seamlessly integrated solution for in vivo microscopic imaging in the brain of awake and moving rodents. The solution is based upon Prior’s ultra-stable and easily adjustable Z-Deck platform.. Neurotar’s Mobile HomeCage is an accessory device for microscopy and electrophysiology, which enables high precision tests in the brain of awake, head-fixed, but otherwise freely moving rodents. The unit eliminates the need for anaesthesia and thus preserves full physiological functioning of the brain. It provides a natural, tangible environment, which alleviates the stress experienced by rodents during experiments under standard head-fixation conditions. Stress reduction helps reduce the run-up time to the start of experiments and improves their reproducibility. The unit is compact – it fits into most imaging set-ups without the need for modifications. Last but not least, it allows combining state-of-the-art neurophysiological techniques (such as in vivo two-photon microscopy, optogenetics, intrinsic optical imaging and in vivo patch-clamp) with behavioral paradigms in a single experiment. Working closely with Neurotar, Prior have developed a fixing kit allowing seamless integration of the unit with the Z-Deck platform. The platform is an ultra-stable, height adjustable platform designed specifically for electrophysiology and microscopy applications in neuroscience, which is available with an integral motorized positioning stage, a manual positioning stage, or a fixed top plate. The platform is compatible with a wide range of microscopes. The new fixing kit allows neuroscientists to combine the benefits offered by the Mobile HomeCage with the stability, height adjustment and operational flexibility offered by the Z-Deck. Importantly, the fixing kit allows the loading of the mouse either on or off the stage followed by a quick and precise re-positioning of the unit onto the platform. This means that the delicate operation of mouse-loading does not need to be performed around the microscope system itself.