Effects of aging on nerve sprouting and regeneration

We examined the effects of aging on nerve terminal sprouting and regeneration in the peripheral nervous system. Motor end-plates were demonstrated in rat soleus muscles by means of a cholinesterase-silver stain which permitted measurement of end-plate length and nerve terminal branching. Terminal sprouting was elicited by “pharmacological denervation” brough about by botulinum toxin treatment. In the youngest (2-month-old) animals, the end-plates were small, and the terminals had simple branch patterns. Botulinum toxin treatment elicited a striking increase in end-plate length and terminal arborization. In the older (10- and 18-month-old) animals, the end-plate length was greater, and nerve terminal branching patterns were more complex. Botulinum toxin elicited a sprouting response that was less marked than in the youngest animals. In the oldest (28-month-old) animals, the end-plates were shorter and the terminals less complex. Botulinum failed to elicit any significant sprouting response. Regeneration of motor and sensory axons after a crush lesion of the sciatic nerve was measured using radiolabeled proteins carried by axonal transport as a marker of axonal outgrowth. Our results showed that the average rate of regeneration slowed with increasing age, although a small population of axons continued to regenerate rapidly regardless of age. Evidence implicating inherent defects in the ability of nerves to sprout and regenerate with increasing age is presented. Our findings in the peripheral nervous system may shed light on similar functional changes occurring in the central nervous system.