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

• DOI: 10.1007/s12035-015-9432-7
• Publication Date: 2015-09-16T07:46:53Z
• Authors: Morgane Louessard; Alexandre Lacroix; Magalie Martineau; Gregoire Mondielli; Axel Montagne; Flavie Lesept; Bertrand Lambolez; Bruno Cauli; Jean-Pierre Mothet; Denis Vivien; Eric Maubert
• Keywords: Cortical neurons; Male; Mice, Knockout; 0303 health sciences; Tissue-type plasminogen activator; Pyramidal Cells; Neurotransmission; Excitatory Postsynaptic Potentials; Gene Expression; Glutamic Acid; Rats; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Organ Culture Techniques; Tissue Plasminogen Activator; Extracellular protease; Animals; [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]; Synaptic Vesicles; Rats, Wistar; Cells, Cultured

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.