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

Abstract

To morphologically define the aging-related features during muscle reinnervation the spatiotemporal relationships among the major components of the neuromuscular junctions (NMJs) were investigated. A total of 64 rats, 30 adults (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 (SCs), for protein gene product 9.5, a neuronal marker, and for ␣-bungarotoxin (␣-BT), a marker of the acetylcholine receptor site (AChR site), and then observed by confocal laser microscopy. The most obvious age changes were noted: (1) the regenerating SCs and axons were delayed in their arrival at the NMJ, (2) the dimensions of terminal SCs and AChR sites displayed a drastic and long-lasting drop (for terminal SCs, during 1-8 weeks; for 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, together 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 innervation, nerve bundles, and NMJs, more frequently occurred in the later reinnervation period. Thus, with aging, regeneration is impaired during the period in which regenerating SC strands and axons extend into NMJs and the subsequent establishment of nerve-muscle contact is in progress. A complex set of morphological abnormalities between or among the TSCs, terminal axons, and AChR sites may be important in slowing of regeneration and reinnervation in aged motor endplates. Anat Rec 264: [183][184][185][186][187][188][189][190][191][192][193][194][195][196][197][198][199][200][201][202] 2001.

Striking Denervation of Neuromuscular Junctions without Lumbar Motoneuron Loss in Geriatric Mouse Muscle

“…However, such changes in SCs will have an adverse effect on the maintenance of the remaining NMJ and possible re-innervation. Most studies have examined alterations in SCs after nerve crush or transection [44], whereas very few have examined SCs in ageing muscles [45], [46]. An electron microscopic study of gastrocnemius muscles in mice showed no SC degeneration in young adults (6 months) but degeneration of SCs and their processes in 35% of the NMJs at 27 months [45].…”

The Neuromuscular Junction: Aging at the Crossroad between Nerves and Muscle

“…Impairment in these cells, such as increased fragmentation, damage, or denervation may contribute to ineffective re-innervation and neuromuscular dysfunction in aging (Verge et al, 1996; Kawabuchi et al, 2001, 2011; Gordon et al, 2009). …”

Perisynaptic Schwann Cells at the Neuromuscular Synapse: Adaptable, Multitasking Glial Cells

“…Enhanced expression of a cell-surface glycoprotein, CD44, in PSCs in an ALS mouse model further suggests a potential role of PSCs in the motor neuron disease (Gorlewicz et al 2009). Impaired PSC sprouting seen in aged muscles may also explain the poor reinnervation after nerve injury during aging (Kawabuchi et al 2001). Besides guiding presynaptic nerve terminals, PSCs are thought to play a role in clustering postsynaptic AChRs by expressing neuronal isoforms of agrin at the frog NMJ (Yang et al 2001).…”