title: Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons.
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.
authors.affiliation: 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.
authors.forename: Morgane
authors.initials: M
authors.lastname: Louessard
authors.affiliation: UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UM 119, Neuroscience Paris Seine, Sorbonne Universités, 75005, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, 75005, Paris, France.|INSERM, UMR-S 1130, Neuroscience Paris Seine, 75005, Paris, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Lacroix
authors.affiliation: Department of Cellular Biophysics, Institute for Medical Physics and Biophysics, University of Muenster, Muenster, Germany.
authors.forename: Magalie
authors.initials: M
authors.lastname: Martineau
authors.affiliation: Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille UMR7286 CNRS, Aix Marseille University, Marseille, France.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Mondielli
authors.affiliation: 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.
authors.forename: Axel
authors.initials: A
authors.lastname: Montagne
authors.affiliation: 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.
authors.forename: Flavie
authors.initials: F
authors.lastname: Lesept
authors.affiliation: UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UM 119, Neuroscience Paris Seine, Sorbonne Universités, 75005, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, 75005, Paris, France.|INSERM, UMR-S 1130, Neuroscience Paris Seine, 75005, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lambolez
authors.affiliation: UPMC Univ Paris 06, Institut de Biologie Paris-Seine (IBPS), UM 119, Neuroscience Paris Seine, Sorbonne Universités, 75005, Paris, France.|CNRS, UMR 8246, Neuroscience Paris Seine, 75005, Paris, France.|INSERM, UMR-S 1130, Neuroscience Paris Seine, 75005, Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cauli
authors.affiliation: Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille UMR7286 CNRS, Aix Marseille University, Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mothet
authors.affiliation: 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. vivien@cyceron.fr.
authors.forename: Denis
authors.initials: D
authors.lastname: Vivien
authors.affiliation: 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.
authors.forename: Eric
authors.initials: E
authors.lastname: Maubert
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D015870:Gene Expression; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D018698:Glutamic Acid; D010959:Tissue Plasminogen Activator
keywords: Cortical neurons; Extracellular protease; Neurotransmission; Tissue-type plasminogen activator