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Effect of substituted dextrans on the synaptogenesis of fast and slow rat skeletal muscles during post-traumatic regeneration
The Latest in Synaptic Transmission
POSTER
365
1
Effect o f s u b s t i t u t e d d e x t r a n s on the s y n a p t o g e n e s i s o f fast and s l o w rat skeletal muscles during post-traumatic regeneration. A. Aamiri, Y. Bassaglia, C. Kedzia, 1. Husmann, A. Meddahi, D. Barritault and J. Gautron. URA CNRS N ° 1813. CRRET. Univ. Paris XII, av. Gal. de Gaulle, 94010 Cr6teil - Cedex. Myogenesis of adult muscles during regeneration differs from muscle differentiation ill foetus. Regeneration takes place in the pattern of the preexisting basal lamina after activation of quiescent satellite cells (Mauro, 1961). This basement membrane is also implicated in the reformation of synapses as an active structure which directs and regulates the neurite growth. Regeneration is preceeded by myolysis induced by endogenous and exogenous neutral and acidic proteases. In previous experiments, using a cruch model, we showed that protease activity was higher in the soleus than in the EDL (Moraczewski). These different levels of proteolysis were correlated with the preservation of basement membrane in regenerated EDL muscle and its partial degradation ill tile slow muscle (Bassaglia, 1994). The well-preserved matrix of EDL permitted a restauration of a functionnai m uscle after 2 months (Carsion, 1976). The regenerating soleus muscle showed many small immature fibers surrounded by their own basement membrane inside of an old altered one. This abnormal structure might explain the non-reinnervation of the slow fibers and the resulting degeneration of soleus after 2 months (Bassaglia, 1994). We experimented several substituted dextrans injected ill crushed EDL and soleus muscles.The "most effective molecule was CMDBS (carboxy methyl dextran benzylamide sulfonate). This molecule revealed an antiprotease activity (Meddahi, 1994) and an affinity for HBGFs factors, mimicking the low affinity receptors, increasing their biodisponibility. This binding also protected the factors against proteolytic degradation (Tardieu, 1992). Just after crush, we injected in the muscle 100 Ill of I'BS contailfing 50 ~4g of (?MI)BS. The rcgcnerati(m and ncosynaptogenesis were compared from 1 tO I(~ days using Ifiochclnic~l (ACHE 16S, CPK), histochemical methods and silver staining tcchnique. After treatment with CMDBS we observed in both muscles a stimulation of the regeneration (number, diameter and differentiation of fibers). The most important effect concerned the soleus muscle. This effect might be the result of a higher degree of activation and fusion of satellite cells induced by the CMDBS. In soleus but also in EDL treated muscles we observed a precocious reappearance of motor end-plates. The surface of the synaptic gutter and its differentiation (folds) was also increased compared to the respective control muscles. The regeneration of soleus was effective and no signs of degeneration or abnormal basement membranes were observed. The fact that a single initial injection was able to stimulate regeneration for a long term suggested a very early action at the level of the matrix pattern and the activation of the satellite cells.The correlative stimulation of the synaptogenesis and the earlier reformation of motor end-plates in both soleus and EDL muscles which didn't show important matrix alterations, suggested a direct action of this molecule on the neurite growth. Bassaglia Y. et al, 1994 submitted. Carslon B.M., 1976, Exp Neurol., 52, 421-432. Gospodorowicz D. et al, 1976, J Cell Biol., 70, 395-405. Meddahi, 1994, Thesis. Moraczewski et al, in preparation. Mauro A., 1961, J. Biophys. Biochem. Cytoi., 9, 493-495. Tardieu M. et al, 1992, J. Cell Physiol., 150, 194-203.
POSTER
365
1
Effect o f s u b s t i t u t e d d e x t r a n s on the s y n a p t o g e n e s i s o f fast and s l o w rat skeletal muscles during post-traumatic regeneration. A. Aamiri, Y. Bassaglia, C. Kedzia, 1. Husmann, A. Meddahi, D. Barritault and J. Gautron. URA CNRS N ° 1813. CRRET. Univ. Paris XII, av. Gal. de Gaulle, 94010 Cr6teil - Cedex. Myogenesis of adult muscles during regeneration differs from muscle differentiation ill foetus. Regeneration takes place in the pattern of the preexisting basal lamina after activation of quiescent satellite cells (Mauro, 1961). This basement membrane is also implicated in the reformation of synapses as an active structure which directs and regulates the neurite growth. Regeneration is preceeded by myolysis induced by endogenous and exogenous neutral and acidic proteases. In previous experiments, using a cruch model, we showed that protease activity was higher in the soleus than in the EDL (Moraczewski). These different levels of proteolysis were correlated with the preservation of basement membrane in regenerated EDL muscle and its partial degradation ill tile slow muscle (Bassaglia, 1994). The well-preserved matrix of EDL permitted a restauration of a functionnai m uscle after 2 months (Carsion, 1976). The regenerating soleus muscle showed many small immature fibers surrounded by their own basement membrane inside of an old altered one. This abnormal structure might explain the non-reinnervation of the slow fibers and the resulting degeneration of soleus after 2 months (Bassaglia, 1994). We experimented several substituted dextrans injected ill crushed EDL and soleus muscles.The "most effective molecule was CMDBS (carboxy methyl dextran benzylamide sulfonate). This molecule revealed an antiprotease activity (Meddahi, 1994) and an affinity for HBGFs factors, mimicking the low affinity receptors, increasing their biodisponibility. This binding also protected the factors against proteolytic degradation (Tardieu, 1992). Just after crush, we injected in the muscle 100 Ill of I'BS contailfing 50 ~4g of (?MI)BS. The rcgcnerati(m and ncosynaptogenesis were compared from 1 tO I(~ days using Ifiochclnic~l (ACHE 16S, CPK), histochemical methods and silver staining tcchnique. After treatment with CMDBS we observed in both muscles a stimulation of the regeneration (number, diameter and differentiation of fibers). The most important effect concerned the soleus muscle. This effect might be the result of a higher degree of activation and fusion of satellite cells induced by the CMDBS. In soleus but also in EDL treated muscles we observed a precocious reappearance of motor end-plates. The surface of the synaptic gutter and its differentiation (folds) was also increased compared to the respective control muscles. The regeneration of soleus was effective and no signs of degeneration or abnormal basement membranes were observed. The fact that a single initial injection was able to stimulate regeneration for a long term suggested a very early action at the level of the matrix pattern and the activation of the satellite cells.The correlative stimulation of the synaptogenesis and the earlier reformation of motor end-plates in both soleus and EDL muscles which didn't show important matrix alterations, suggested a direct action of this molecule on the neurite growth. Bassaglia Y. et al, 1994 submitted. Carslon B.M., 1976, Exp Neurol., 52, 421-432. Gospodorowicz D. et al, 1976, J Cell Biol., 70, 395-405. Meddahi, 1994, Thesis. Moraczewski et al, in preparation. Mauro A., 1961, J. Biophys. Biochem. Cytoi., 9, 493-495. Tardieu M. et al, 1992, J. Cell Physiol., 150, 194-203.