Fast Axoplasmic Transport of Acetylcholinesterase in Mammalian Nerve Fibres

Abstract

Acetylcholinesterase (acetylcholine acetyl-hydrolase, EC 3.1.1.7) is carried down mammalian nerve fibres by the fast axoplasmic transport system. This conclusion was derived from experiments involving the ligation of cat sciatic nerves at two sites placed 8 3 3 mm apart. The enzyme accumulated in segments of nerve proximal to the upper ligation in a linear fashion over a period of at least 20 h. At approximately 5 h the accumulation of enzyme ceased in the nerve segment proximal to the distal ligation within the isolated length of nerve, an observation indicating that the portion of AChE free to move within the isolated nerve had been depleted during this period of time. The freely moving fraction of AChE was estimated to be 15 % of the total enzyme activity present in the nerve (10% in the proximo-distal direction and 5 % in the retrograde direction). The rate of AChE downflow (as estimated from the intercept of the curve plotting accumulation with the line denoting when depletion started) was 431 mm/day within a 95% confidence interval of 357-543 mm/day. In view of the variability, our results demonstrated that AChE was being carried by the fast axoplasmic transport system, which in earlier studies was estimated to have a characteristic rate close to 410 mm/day. An accumulation of AChE was also found on the distal side of the ligations that represented a movement of AChE in the distal-proximal direction in the fibres. This retrograde transport was smaller in amount (about one-half) than the proximo-distal rate of transport, or close to 220 mm/day. The rate of AChE transport was discussed in relation to the 'transport filament' hypothesis of fast axoplasmic transport.

Normal distribution and denervation changes of neurotransmitter related enzymes in cholinergic neurones

“…This prompted the speculation that the fraction of AChE changed is the mobile fraction carried by fast axonal flow (Ranish & Ochs, 1972). Recently, Somogyi & Chubb (1976) have concluded that in the superior cervical ganglion the preganglionic nerves seem able to regulate the total amount of AChE contained in ganglion cells.…”

“…Another explanation for the lesser decrease of AChE might be that a large fraction of the enzyme activity measured represents the stationary fraction, mainly membrane bound (Lubinska & Niemierko, 1971). Ranish & Ochs (1972) have calculated that, in the cat sciatic nerve, the freely moving fraction of AChE is 15% of the total enzyme present. This low percentage of fast-moving AChE may reflect a slower turnover of the enzyme; and since the AChE turnover is slower, there is not as great a need for enzyme to be transported to the terminals.…”

Axotomy Upregulates the Anterograde Transport and Expression of Brain-Derived Neurotrophic Factor by Sensory Neurons

“…To visualize and quantif y anterograde and retrograde transport of endogenous neurotrophins and neuropeptides, we performed a doubleligation procedure that has been used previously to examine axonal transport of acetylcholinesterase, neurotransmitters, and neurotrophins in the sciatic nerve (Ranish and Ochs, 1972;Ben-Jonathan et al, 1978;Johnson et al, 1987;Z hou and Rush, 1996). Ligations consisted of two 4 -0 silk ligatures tied tightly around the sciatic nerve 0.5 cm apart, ϳ1 cm distal to the tendon of the obturator internus muscle.…”

Ultrastructural Study of Anterograde Transport of Glial Cell Line-Derived Neurotrophic Factor from Dorsal Root Ganglion Neurons of Rats towards the Nerve Terminal

“…This method has been commonly used to examine the axonal transport of neurotransmitters and neurotrophins in the PNS [Ranish and Ochs, 1972;Ben-Jonathan et al, 1978;Johnson et al, 1987;Tonra et al, 1998]. The ligation consisted of two 4-0 silk ligatures tied tightly around the sciatic nerve 4 mm apart at mid thigh level.…”