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Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons

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Abstract

Although the extracellular serine protease tissue plasminogen activator (tPA) is involved in pathophysiological processes such as learning and memory, anxiety, epilepsy, stroke, and Alzheimer’s disease, information about its regional, cellular, and subcellular distribution in vivo is lacking. In the present study, we observed, in healthy mice and rats, the presence of tPA in endothelial cells, oligodendrocytes, mastocytes, and ependymocytes, but not in pericytes, microglial cells, and astrocytes. Moreover, blockage of the axo-dendritic transport unmasked tPA expression in neurons of cortical and hippocampal areas. Interestingly, combined electrophysiological recordings, single-cell reverse transcription polymerase chain reaction (RT-PCR), and immunohistological analyses revealed that the presence of tPA is restricted to subsets of excitatory pyramidal glutamatergic neurons. We further evidenced that tPA is stored in synaptobrevin-2-positive glutamatergic synaptic vesicles. Based on all these data, we propose the existence of tPA-ergic neurons in the mature brain.

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Acknowledgments

This work was supported by grants from the INSERM (French National Institute for Health and Medical Research) (D.V.), the University of Caen Basse-Normandie (D.V.), Era-net Neuron program “ProteA” EU FP7 (D.V.), ANR 2011 MALZ 003 01 (B.C.), and “IHU Institut de Neurosciences Translationelles de Paris,” ANR-10-IAIHU-06 (B.C. and B.L.). Part of this work was coordinated by CEA/MIRCen/IB2M and supported by the association France Alzheimer (B.C.). G.M. is supported by a grant from the Fondation pour la Recherche Médicale and J-P.M. receives operating grants from Centre National de la Recherche Scientifique, France Alzheimer, and Université Aix-Marseille. The authors also thanks Pr.Carine ALI for her suggestions during the elaboration of the manuscript.

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    1. INSERM, UMR-S 919, Serine Proteases and Pathophysiology of the Neurovascular Unit, Université Caen Basse-Normandie, GIP Cyceron, Bvd Henri Becquerel, GIP Cyceron, 14074, Caen, France

      Morgane Louessard, Axel Montagne, Flavie Lesept, Denis Vivien & Eric Maubert

    2. UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UM 119, Neuroscience Paris Seine, Sorbonne Universités, 75005, Paris, France

      Alexandre Lacroix, Bertrand Lambolez & Bruno Cauli

    3. CNRS, UMR 8246, Neuroscience Paris Seine, 75005, Paris, France

      Alexandre Lacroix, Bertrand Lambolez & Bruno Cauli

    4. INSERM, UMR-S 1130, Neuroscience Paris Seine, 75005, Paris, France

      Alexandre Lacroix, Bertrand Lambolez & Bruno Cauli

    5. Department of Cellular Biophysics, Institute for Medical Physics and Biophysics, University of Muenster, Muenster, Germany

      Magalie Martineau

    6. Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille UMR7286 CNRS, Aix Marseille University, Marseille, France

      Gregoire Mondielli & Jean-Pierre Mothet

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    Denis Vivien and Eric Maubert contributed equally to this work.

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    Louessard, M., Lacroix, A., Martineau, M. et al. Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons. Mol Neurobiol 53, 5000–5012 (2016). https://doi.org/10.1007/s12035-015-9432-7

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