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

Mol Neurobiol. 2016 Sep;53(7):5000-12. doi: 10.1007/s12035-015-9432-7. Epub 2015 Sep 16.


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.

Keywords: Cortical neurons; Extracellular protease; Neurotransmission; Tissue-type plasminogen activator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / physiology*
  • Gene Expression
  • Glutamic Acid / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Culture Techniques
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Wistar
  • Synaptic Vesicles / metabolism*
  • Tissue Plasminogen Activator / biosynthesis*
  • Tissue Plasminogen Activator / genetics


  • Glutamic Acid
  • Tissue Plasminogen Activator