Age affects reciprocal cellular interactions in neuromuscular synapses following peripheral nerve injury

Studies of the influence of age on regeneration and reinnervation in the peripheral nervous system (PNS) and neuromuscular junction (NMJ) are reviewed, with a particular focus on aged and denervated skeletal muscles. The morphological and functional features of incomplete regeneration and reinnervation are compared between adult and aged animals. In addition, some possible mechanisms of the age-related defects will be discussed. Increased fragmentation or damage in individual components of the NMJ (terminal Schwann cells (TSCs), axon terminals and acetylcholine receptor sites occurs during muscle reinnervation following PNS injury in the aged animals. The capacity to produce ultraterminal sprouting or multiple innervation secondary to PNS injury is maintained, but not the capacity to eliminate such anomalous axonal profiles. The frequency and accuracy of reoccupation of the synaptic sites by TSCs and axon terminals are impaired. Thus, despite the capability of extending neural processes, the rate at which regenerating nerve fibers grow, mature and precisely appose the postsynaptic muscle fiber is impaired, resulting in the failure of re-establishment of the normal single motor innervation in the NMJ. A complex set of cellular interactions in the NMJ are known to participate in the neurotrophism and neurotrophism to support growth of the regenerating and sprouting axons and their pathfinding to direct the target muscle fiber. Besides the capability of α-motoneurons, signaling originating from the TSCs and muscle may be impaired during aging.

Research highlights▶ Animal model was focused on nerve crushing injury with some age-related features of intramuscular nerve branching and the axonal growth profiles in the regenerating nerve fibbers, together with those of re-establishment of motor reinnervation at the NMJ. ▶ Timing of nerve repair showed a delay in Wallerian degeneration due to reduced reactivity of the nonneuronal cells with aging. ▶ The incompleted regeneration and reinnervation with aging occurred in damaged and poor formation in the terminal Schwann cell, terminal axon, acetylcholine sites and degenerated junctional folds. ▶ The capacity to develop the synapse elimination was reduced in aging animal on the basis of impaired outgrowth of TSC processes and terminaI sprouting as well as the more frequent occurrence of multiple innervation.