AXONAL TRANSPORT OF SELECTED PARTICLE-SPECIFIC ENZYMES IN RAT SCIATIC NERVE IN VIVO AND ITS RESPONSE TO INJURY

Abstract— Orthograde and retrograde axoplasmic transport of selected axonal organelles were examined by monitoring accumulation of enzyme activities residing in various types of particles proximal and distal to a ligature placed on rat sciatic nerve as a function of time after tying. Proximal to the tie, activity of acetylcholinesterase (AChE, EC 3.1.1.7; probably in small endoplasmic reticulum-like particles) accumulated for 2 days; then, during the next 5 days, the accumulation disappeared. Activities of glutamic dehydrogenase (GDH, EC 1.4.1.3) and monoamine oxidase (MAO, EC 1.4.3.4) (both located in mitochondria) accumulated steadily for 7 days. Accumulation of monoamine oxidase activity was more rapid than that of glutamic dehydrogenase during the first day or two. Acid phosphatase (acid P'tase, EC 3.1.3.2; in lysosomes) activity also accumulated throughout the week of observation. Accumulation of all four enzyme activities proximal to the ligature was blocked by nerve crush or subepineurial vinblastine injection 1 cm or more proximal to the site of the tie. Distal to the ligature, AChE activity accumulated early (14 h), and then gradually disappeared in the course of the week. MAO activity also accumulated, with a maximum at 2 days, and no further change thereafter. GDH activity, on the other hand, showed little accumulation during the first 2 days, but did appear in modest amounts at the end of the week. Distal accumulation of acid P'tase kept pace with proximal accumulation for the first day, and continued more slowly for another day, after which there was no further change. This system has been used to study the effects of axonal crush injury upon anterograde and retrograde axoplasmic transport. A tie applied at various times after injury, proximal to the site of injury, was used to show that orthograde transport of AChE was maintained for 1 day after tying, but at 2 days had fallen 50% or more, and within a week was down to 20–25% of control. At 3 days after injury retrograde transport of AChE activity was not different from the control. Orthograde transport of acid P'tase activity was depressed 35% by injury. Retrograde transport of acid P'tase was inhibited more than 50% both at 3 and at 7 days after injury. Transport of the mitochondrial enzymes was not measurably affected.