EXPRESSION OF NEUROSERPIN, AN INHIBITOR OF TISSUE-PLASMINOGEN ACTIVATOR, IN THE DEVELOPING AND ADULT NERVOUS-SYSTEM OF THE MOUSE

Neuroserpin is a serine protease inhibitor of the serpin family that h as been identified as an axonally secreted glycoprotein in neuronal cu ltures of chicken dorsal root ganglia. To obtain an indication for pos sible functions of neuroserpin, we analyzed its expression in the deve loping and the adult CNS of the mouse. In the adult CNS, neuroserpin w as most strongly expressed in the neocortex, the hippocampal formation , the olfactory bulb, and the amygdala. In contrast, most thalamic nuc lei, the caudate putamen, and the cerebellar granule cells were devoid of neuroserpin mRNA. During embryonic development, neuroserpin mRNA w as not detectable in neuroepithelia, but it was expressed in the diffe rentiating fields of most CNS regions concurrent with their appearance . In the cerebellum, the granule cells and a subgroup of Purkinje cell s were neuroserpin-positive during postnatal development. As a further step toward the elucidation of neuroserpin function, we performed a s tudy to identify potential target proteases. In vitro, neuroserpin for med SDS-stable complexes and inhibited the amidolytic activity of tiss ue plasminogen activator, urokinase, and plasmin. In contrast, no comp lex formation with or inhibition of thrombin was found. Expression pat tern and inhibitory specificity implicate neuroserpin as a candidate r egulator of plasminogen activators, which have been suggested to parti cipate in the modulation or reorganization of synaptic connections in the adult. During development, neuroserpin may attenuate extracellular proteolysis related to processes such as neuronal migration, axogenes is, or the formation of mature synaptic connections.