Genetic Mutation Accelerates CTE Pathology

Phosphorylated tau pS422 immunoreactive profiles in the cortex of P301Smice after repetitive mild TBI. Image courtesy of Dr. Leyan Xu.

Phosphorylated tau pS422 immunoreactive profiles (dark brown) in the cortex of P301S mice after repetitive mild TBI. Image courtesy of Dr. Leyan Xu, Department of Pathology, Johns Hopkins University.

Over the course of a football game or a boxing match, athletes may experience a series of mild concussions. Some of these athletes develop a condition known as chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by the build-up of abnormal tau protein that eventually leads to dementia. But not every athlete develops CTE after repetitive mild traumatic brain injury, and scientists think genetic factors are involved.

In a recent study, researchers at the Johns Hopkins University School of Medicine found that the density of abnormal tau protein increased exponentially in mice that had a genetic mutation thought to cause neurodegenerative diseases. Their findings contrast with previous studies of mice without genetic mutation, where abnormal tau protein build-up did not occur. This evidence leads the scientists to infer that genetic factors play a role in the onset of CTE.

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Researchers cited MBF systems in 13 papers during the week of 2/1/2016

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Benskey, M., Sandoval, I. M., & Manfredsson, F. P. (2016). Continuous Collection of AAV from Producer Cell Media Significantly Increases Total Viral Yield. Human Gene Therapy Methods. doi: 10.1089/hgtb.2015.117.

Chan, E. C., Van Wijngaarden, P., Chan, E., Ngo, D., Wang, J.-h., Peshavariya, H. M., . . . Liu, G.-S. (2016). NADPH oxidase 2 plays a role in experimental corneal neovascularisation. [10.1042/CS20150103]. Clinical Science.

Coimbra, J. P., Kaswera-Kyamakya, C., Gilissen, E., Manger, P. R., & Collin, S. P. (2016). The Topographic Organization of Retinal Ganglion Cell Density and Spatial Resolving Power in an Unusual Arboreal and Slow-Moving Strepsirhine Primate, the Potto (Perodicticus potto). Brain, Behavior and Evolution.

Filice, F., Vörckel, K. J., Sungur, A. Ö., Wöhr, M., & Schwaller, B. (2016). Reduction in parvalbumin expression not loss of the parvalbumin-expressing GABA interneuron subpopulation in genetic parvalbumin and shank mouse models of autism. Molecular Brain, 9(1), 1-17. doi: 10.1186/s13041-016-0192-8.

Hall, J. M., & Savage, L. M. (2016). Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior. Experimental Neurology. doi: http://dx.doi.org/10.1016/j.expneurol.2016.01.018.

Hassouna, I., Ott, C., Wustefeld, L., Offen, N., Neher, R. A., Mitkovski, M., . . . Ehrenreich, H. (2016). Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus. Molecular Psychiatry. doi: 10.1038/mp.2015.212.http://dx.doi.org/10.1038/mp.2015.212

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Researchers cited MBF systems in 18 papers during the week of 1/25/2016

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Hackett, A. R., Lee, D.-H., Dawood, A., Rodriguez, M., Funk, L., Tsoulfas, P., & Lee, J. K. (2016). STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury. Neurobiology of Disease. doi: http://dx.doi.org/10.1016/j.nbd.2016.01.017.

Karuppagounder, S. S., Xiong, Y., Lee, Y., Lawless, M. C., Kim, D., Nordquist, E., . . . Dawson, V. L. (2016). LRRK2 G2019S Transgenic Mice Display Increased Susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Mediated Neurotoxicity. Journal of Chemical Neuroanatomy. doi:http://dx.doi.org/10.1016/j.jchemneu.2016.01.007.

Mustafa, S., Martin, H. L., Burkly, L., Costa, A., Martins, M. L., Schwaninger, M., & Teismann, P. (2016). The role of TWEAK/Fn14 signaling in the MPTP-model of Parkinson’s disease. Neuroscience. doi:http://dx.doi.org/10.1016/j.neuroscience.2016.01.034.

Spencer, B., Potkar, R., Metcalf, J., Thrin, I., Adame, A., Rockenstein, E., & Masliah, E. (2016). Systemic Central Nervous System (CNS)-targeted Delivery of Neuropeptide Y (NPY) Reduces Neurodegeneration and Increases Neural Precursor Cell Proliferation in a Mouse Model of Alzheimer Disease. Journal of Biological Chemistry, 291(4), 1905-1920. doi: 10.1074/jbc.M115.678185.

Vistoropsky-Katz, Y., Heiblum, R., Smorodinsky, N.-I., & Barnea, A. (2016). Active immunization against vasoactive intestinal polypeptide decreases neuronal recruitmetnt and inhibits reproduction in zebra finches. Journal of Comparative Neurology, n/a-n/a. doi: 10.1002/cne.23971.

Neurolucida:

Borrett, S., & Hughes, L. (2016). Reporting methods for processing and analysis of data from serial block face scanning electron microscopy. Journal of Microscopy, n/a-n/a. doi: 10.1111/jmi.12377.

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Researchers cited MBF systems in 16 papers during the week of 1/18/2016

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Bradshaw, S. E., Agster, K. L., Waterhouse, B. D., & McGaughy, J. A. (2016). Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats. Brain Research. doi: http://dx.doi.org/10.1016/j.brainres.2016.01.001.

Chen, G.-H., Teitz-Tennenbaum, S., Neal, L. M., Murdock, B. J., Malachowski, A. N., Dils, A. J., . . . Osterholzer, J. J. (2016). Local GM-CSF–Dependent Differentiation and Activation of Pulmonary Dendritic Cells and Macrophages Protect against Progressive Cryptococcal Lung Infection in Mice. The Journal of Immunology. doi: 10.4049/jimmunol.1501512.

Chermenina, M., Chorell, E., Pokrzywa, M., Antti, H., Almqvist, F., Strömberg, I., & Wittung-Stafshede, P. (2015). Single injection of small-molecule amyloid accelerator results in cell death of nigral dopamine neurons in mice. Npj Parkinson’s Disease, 1, 15024. doi: 10.1038/npjparkd.2015.24

King, S. J., Rodrigues, T., Watts, A., Murray, E., & Abizaid, A. (2016). Investigation of a role for ghrelin signaling in binge-like feeding in mice under limited access to high-fat diet. Neuroscience. doi:http://dx.doi.org/10.1016/j.neuroscience.2016.01.004.

Moorman, D. E., James, M. H., Kilroy, E. A., & Aston-Jones, G. (2016). Orexin/hypocretin neuron activation is correlated with alcohol seeking and preference in a topographically specific manner. European Journal of Neuroscience, n/a-n/a. doi: 10.1111/ejn.13170. http://dx.doi.org/10.1111/ejn.13170

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Researchers cited MBF systems in 19 papers during the week of 1/11/2016

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Jiang, Y.-Q., Zaaimi, B., & Martin, J. H. (2016). Competition with Primary Sensory Afferents Drives Remodeling of Corticospinal Axons in Mature Spinal Motor Circuits. The Journal of Neuroscience, 36(1), 193-203.

Jin, H., Chen, T., Li, G., Wang, C., Zhang, B., Cao, X., . . . Chen, L. (2016). Dose-Dependent Neuroprotection and Neurotoxicity of Simvastatin through Reduction of Farnesyl Pyrophosphatein Mice Treated with Intracerebroventricular Injection of Aβ 1-42. Journal of Alzheimer’s Disease(Preprint), 1-16.

Maduka, U. P., Hamity, M. V., Walder, R. Y., White, S. R., Li, Y., & Hammond, D. L. (2016). Changes in the disposition of substance P in the rostral ventromedial medulla after inflammatory injury in the rat. Neuroscience. doi: http://dx.doi.org/10.1016/j.neuroscience.2015.12.054.

Özay, R., Yavuz, O. Y., Türko lu, M. E., Akta_, A., Yi it, F., Özdemir, H. M., & ekerci, Z. (2015). The effects of ankaferd blood stopper and microporous polysaccharide hemospheres on epidural fibrosis in rat laminectomy model. Acta Cirurgica Brasileira, 30, 799-805.

Pardo, M., Abrial, E., Jope, R. S., & Beurel, E. (2016). GSK3β isoform-selective regulation of depression, memory and hippocampal cell proliferation. Genes, Brain and Behavior, n/a-n/a. doi: 10.1111/gbb.12283.

Saal, K.-A., Galter, D., Roeber, S., Bähr, M., Tönges, L., & Lingor, P. (2015). Altered Expression of Growth Associated Protein-43 and Rho Kinase in Human Patients with Parkinson’s Disease. Brain Pathology, n/a-n/a. doi: 10.1111/bpa.12346.

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Researchers cited MBF systems in 34 papers between 12/21/2015 and 1/8/2016

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Ayranci, F., Gungormus, M., Omezli, M. M., & Gundogdu, B. (2015). The Effect of Alendronate on Various Graft Materials Used in Maxillary Sinus Augmentation: A Rabbit Study. Iran Red Crescent Med J, 17(12), e33569. doi: 10.5812/ircmj.33569.

Cheng, T., Wang, W., Li, Q., Han, X., Xing, J., Qi, C., . . . Wang, J. (2015). Cerebroprotection of Flavanol (-)-Epicatechin after Traumatic Brain Injury via Nrf2-dependent and –independent Pathways. Free Radical Biology and Medicine. doi: http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.027.

Cobb, J. A., O’Neill, K., Milner, J., Mahajan, G. J., Lawrence, T. J., May, W. L., . . . Stockmeier, C. A. (2015). Density of GFAP-immunoreactive astrocytes is decreased in left hippocampi in major depressive disorder. Neuroscience. doi: http://dx.doi.org/10.1016/j.neuroscience.2015.12.044.

Das, S. K., Baitharu, I., Barhwal, K., Hota, S. K., & Singh, S. B. (2016). Early mood behavioral changes following exposure to monotonous environment during isolation stress is associated with altered hippocampal synaptic plasticity in male rats. Neuroscience Letters, 612, 231-237. doi:http://dx.doi.org/10.1016/j.neulet.2015.12.038.

Fan, Z., Lu, M., Qiao, C., Zhou, Y., Ding, J.-H., & Hu, G. (2015). MicroRNA-7 Enhances Subventricular Zone Neurogenesis by Inhibiting NLRP3/Caspase-1 Axis in Adult Neural Stem Cells. Molecular Neurobiology, 1-13. doi: 10.1007/s12035-015-9620-5.

Kanigel Winner, K., Steinkamp, M. P., Lee, R. J., Swat, M., Muller, C. Y., Moses, M. E., . . . Wilson, B. S. (2015). Spatial modeling of drug delivery routes for treatment of disseminated ovarian cancer. Cancer Research. doi: 10.1158/0008-5472.can-15-1620.

Liu, M.-L., Zang, T., & Zhang, C.-L. (2016). Direct Lineage Reprogramming Reveals Disease-Specific Phenotypes of Motor Neurons from Human ALS Patients. Cell Reports. doi:http://dx.doi.org/10.1016/j.celrep.2015.12.018.

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Researchers cited MBF systems in 23 papers during the week of 12/14/2015

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Altunkaynak, B. Z., Altun, G., Yahyazadeh, A., Kaplan, A. A., Deniz, O. G., Türkmen, A. P., . . . Kaplan, S. (2015). Different Methods for Evaluating the Effects of Microwave Radiation Exposure on the Nervous System. Journal of Chemical Neuroanatomy. doi: http://dx.doi.org/10.1016/j.jchemneu.2015.11.004.

Cikla, U., Chanana, V., Kintner, D. B., Covert, L., Dewall, T., Waldman, A., . . . Ferrazzano, P. (2015). Suppression of microglia activation after hypoxia-ischemia results in age-dependent improvements in neurologic injury. Journal of Neuroimmunology, 291, 18-27. doi: 10.1016/j.jneuroim.2015.12.004.

Collins, S. A., Huff, C., Chiaia, N., Gudelsky, G. A., & Yamamoto, B. K. (2015). MDMA Increases Excitability in the Dentate Gyrus: Role of 5HT2A Receptor Induced PGE2 Signaling. Journal of Neurochemistry, n/a-n/a. doi: 10.1111/jnc.13493.

Fox, J., Lu, Z., & Barrows, L. (2015). Thiol-disulfide Oxidoreductases TRX1 and TMX3 Decrease Neuronal Atrophy in a Lentiviral Mouse Model of Huntington’s Disease. PLoS currents, 7, ecurrents.hd.b966ec962eca968e962d989d962bb964d020be4351e. doi: 10.1371/currents.hd.b966ec2eca8e2d89d2bb4d020be4351e.

FRIEDRICH, R. E., BEHRENDT, C.-A., GLATZEL, M., & HAGEL, C. (2015). Vascular Innervation in Benign Neurofibromas of Patients with Neurofibromatosis Type 1. Anticancer Research, 35(12), 6509-6516.

Jones, S., Stanić, D., & Dutschmann, M. (2015). Dorsal and ventral aspects of the most caudal medullary reticular formation have differential roles in modulation and formation of the respiratory motor pattern in rat. Brain Structure and Function, 1-16. doi: 10.1007/s00429-015-1165-x.

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Researchers cited MBF systems in 30 papers between 11/30/2015 and 12/11/2015

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Auvergne, R., Wu, C., Connell, A., Au, S., Cornwell, A., Osipovitch, M., . . . Goldman, S. A. (2015). PAR1 inhibition suppresses the self-renewal and growth of A2B5-defined glioma progenitor cells and their derived gliomas in vivo. Oncogene. doi: 10.1038/onc.2015.452.

Furlanetti, L. L., Coenen, V. A., & Döbrössy, M. D. (2016). Ventral tegmental area dopaminergic lesion-induced depressive phenotype in the rat is reversed by deep brain stimulation of the medial forebrain bundle. Behavioural Brain Research, 299, 132-140.

Ghiglieri, V., Mineo, D., Vannelli, A., Cacace, F., Mancini, M., Pendolino, V., . . . Picconi, B. (2016). Modulation of serotonergic transmission by eltoprazine in L-DOPA-induced dyskinesia: Behavioral, molecular, and synaptic mechanisms. Neurobiology of Disease, 86, 140-153. doi: http://dx.doi.org/10.1016/j.nbd.2015.11.022.

Karadimas, S. K., Laliberte, A. M., Tetreault, L., Chung, Y. S., Arnold, P., Foltz, W. D., & Fehlings, M. G. (2015). Riluzole blocks perioperative ischemia-reperfusion injury and enhances postdecompression outcomes in cervical spondylotic myelopathy. [10.1126/scitranslmed.aac6524]. Science translational medicine, 7(316), 316ra194-316ra194.

Kuzdas-Wood, D., Fellner, L., Premstaller, M., Borm, C., Bloem, B., Kirik, D., . . . Stefanova, N. (2015). Overexpression of α-synuclein in oligodendrocytes does not increase susceptibility to focal striatal excitotoxicity. BMC Neuroscience, 16(1), 86.

Modo, M., Kevin Hitchens, T., Liu, J. R., & Richardson, R. M. (2015). Detection of aberrant hippocampal mossy fiber connections: Ex vivo mesoscale diffusion MRI and microtractography with histological validation in a patient with uncontrolled temporal lobe epilepsy. Human Brain Mapping, n/a-n/a. doi: 10.1002/hbm.23066

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The U.S. Small Business Administration Publishes MBF Bioscience Success Story

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The U.S. Small Business Administration recently published a success story about MBF Bioscience. The article highlights our success using federal Small Business Innovation Research (SBIR) grants to develop innovative products that help advance science. MBF Bioscience has a distinguished R&D program that develops cutting-edge tools for scientific research.

The SBIR grants have helped MBF Bioscience develop tools such as Neurolucida, the most widely used system for neuron reconstruction and analysis, and Stereo Investigator, the gold standard for quantifying the number, area, and volume of neurons. MBF Bioscience has grown significantly since it was awarded its first SBIR grant in 1987. It is now a global company helping scientists around the world discover new information about the brain. The full success story written about MBF Bioscience can be found here.

New Software Released for Automated Neuron Reconstruction and Analysis

montage for email invitationHow the brain works and how the brain is affected by disease are mysteries in large part because neurons are so dynamic, numerous, and complex. Neurolucida 360, a revolutionary, new software product from MBF Bioscience, enables neuroscientists to uncover more information about neurons at a faster rate.

“Neurolucida 360 is a technological revolution” says Jack Glaser, President of MBF Bioscience. “It is the state-of-the-art tool for neuroscientists to analyze the shape and connectivity of neurons more quickly and accurately than has ever been possible, so that we can better understand the brain and the mechanisms behind diseases such as Alzheimer’s and Parkinson’s. With the unique ability to automatically detect and analyze dendrites, dendritic spines, axons, somas, and synapses, Neurolucida 360 is now the standardized platform for the global neuroscience research community to perform unprecedented investigations into the functioning of the brain.”

Using automated tools in Neurolucida 360, researchers generate high-resolution, digital 3D reconstructions of neurons imaged with numerous microscopy techniques, including light sheet, 2 photon, confocal and brightfield. Using the most advanced algorithms for neuron reconstruction, researchers instantly receive hundreds of analyses about the size, shape, and complexity of neurons. The reliable data from Neurolucida 360 is integral to learning how injury, disease, or chemicals change neuronal structure, discovering how neuronal structure affects function, finding out which brain regions neurons communicate with, and more.

The National Institute of Mental Health provides funding to support the development of Neurolucida 360. It is the latest development in the renowned legacy of neuron tracing tools that started with Neurolucida – the most widely cited tool for neuron reconstruction and analysis.

For more information on Neurolucida 360, please visit our website or watch this short video.