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.

Background:The antigenic specificity of scorpion ␣-toxins, which target Na v channels, hinders efficient antiserum production. Results: Structures of two antibodies, which together neutralize the main toxins in a threatening venom, were solved in toxin-bound and unbound forms, respectively. Conclusion: Selective toxin trapping involves distinctive molecular determinants and bound toxin orientations. Significance: These complementary templates will help design new neutralizing molecules suitable for immunotherapy.