CHANGES IN THE EXPRESSION OF PROTEASE-ACTIVATED RECEPTOR-1 AND PROTEASE NEXIN-1 MESSENGER-RNA DURING RAT NERVOUS-SYSTEM DEVELOPMENT AND AFTER NERVE LESION

Thrombin causes profound metabolic and morphological changes in cultur ed neural cells via activation of the thrombin receptor, also called p rotease-activated receptor 1 (PAR1). PAR1 mRNA is present in the rat b rain, but the role of this receptor in the nervous system remains elus ive. The expression of PAR1 and the potent thrombin inhibitor protease nexin-1 (PN-1) was investigated in the developing rat brain and spina l cord and after peripheral nerve lesion. As seen by in situ hybridiza tion, the PAR1 mRNA signal in the late embryonic and early postnatal n ervous system was widespread, but generally of low intensity whereas i n the adult it was more pronounced and confined to particular neuronal cells. These include the mesencephalic dopaminergic neurons, several thalamic and brainstem nuclei, the mitral cells in the olfactory bulb and the Purkinje cells in the cerebellum. In the spinal cord, PAR1 mRN A was abundant in motoneurons and a particularly high expression was d etected in the preganglionic neurons of the autonomic nervous system. High PAR1 mRNA expression was also found in the dorsal root ganglia. I nterestingly, strong immunoreactivity for the protease inhibitor PN-1 was present in spinal motoneuron cell bodies, although its transcript was undetectable there. In response to sciatic nerve transection, the signal intensity of PAR1 mRNA as seen by Northern analysis increased i n the proximal and the distal part of the lesioned nerve and in the de nervated muscle, whereas the PN-1 mRNA signal strongly increased only in the distal part of the nerve but remained unchanged in the proximal part and in the muscle. After facial nerve transection, PAR1 mRNA exp ression substantially decreased in facial motoneurons, No PAR1 transcr ipt was detected in reactive astrocytes. Similar to PAR1, PN-1 mRNA wh ich was expressed in interneurons within the facial nucleus was also d ecreased following facial nerve transection.