The spatiotemporal relationship among Schwann cells, axons and postsynaptic acetylcholine receptor regions during muscle reinnervation in aged rats

To morphologically define the aging-related features during muscle reinnerv ation the spatiotemporal relationships among the major components of the ne uromuscular junctions (NMJs) were investigated. A total of 64 rats, 30 adul ts (4 months old) and 34 aged adults (24 months old), were used. Between 1 and 12 weeks after sciatic nerve-crushing injury, cryosections of skeletal muscle were single or double labeled for S100, a marker of Schwann cells (S Cs), for protein gene product 9.5, a neuronal marker, and for alpha -bungar otoxin (alpha -BT), a marker of the acetylcholine receptor site (AChR site) , and then observed by confocal. laser microscopy. The most obvious age cha nges were noted: (1) the regenerating SCs and axons were delayed in their a rrival at the NMJ, (2) the dimensions of terminal SCs and AChR sites displa yed a drastic and long-lasting drop (for terminal SCs, during 1-8 weeks; fo r AChR sites, during 1-12 weeks); (3) the degree of spatial overlap between AChR sites and terminal SCs was markedly low until 8 weeks post-crush; (4) damage and poor formation in the SCs, terminal axons and AChR sites, toget her with poor process extension from the terminal SC or terminal axon, were pronounced; (5) persistent aberrant changes, such as multiple innervation and terminal axon sprouting, together with poorly formed collateral innerva tion, nerve bundles, and NMJs, more frequently occurred in the later reinne rvation period. Thus, with aging, regeneration is impaired during the perio d in which regenerating SC strands and axons extend into NMJs and the subse quent establishment of nerve-muscle contact is in progress. A complex set o f morphological abnormalities between or among the TSCs, terminal axons, an d AChR sites may be important in slowing of regeneration and reinnervation in aged motor endplates. Anat Ree 264:183-202, 2001. (C) 2001 Wiley-Liss, I nc.