Axonal Transport and Neurotropism

Axonal Transport

Anterograde axonal transport – the movement of material away from the soma toward the synaptic terminal

demonstrated by axonal constriction; material and axoplasm accumulate proximal to the lesion
radiolabeled amino acids exterior to soma taken up and made into polypeptides reveal polypeptides move down axon in distinct waves

Fast Axonal Transport – 200-400mm/day – vesicular structures, synaptic vesicles, neuropeptides, transmitters and associated enzymes

Slow axonal flow:

Retrograde axonal transport – the movement of material from the nerve terminal to the cell body

rate = fast (100-200mm/day)
contains prelysosomal vesicles, growth factors, and recycled proteins from fast retrograde
provides neuron info about peripheral field or target or even nourishment
can aid in determining neuronal connections-i.e. horseradish peroxidase taken up at terminal will eventually be detected in cell body
conveys pathogens from the peripheral targets to cell bodies in CNS (i.e. herpes, rabies viruses, and tetanus toxin)

Cellular and Molecular Mechanism of Transport

slow axonal transport: microtubules and neurofilaments move out slowly as a matrix, replenishing axonal cytoskeleton

kinesin – motor protein that transports vesicles and organelles distally down axon along microtubules (+)

dynein – less well characterized motor protein that likely facilitates retrograde transport to cell body (-)

Importance of axonal transport – 1d post axonal block:

Neurotropism

refers to long term influence of neuron on the molecular properties of its target cells

Example: alpha-motorneuron and muscle

motorneuron contact induces:

AchRs become concentrated at the site of contact due to Ý synthesis and insertion – lost from non synaptic regions

myasthenia gravis: muscular weakness due to ß AchRs because they are covered by antibody

AchE concentrates in the basal lamina of synapse

nerve gas blocks AchE resulting in uncontrolled contraction of many muscles including respiratory – fatal

junctional structures such as synaptic fold and specialized basal lamina Þ efficient transmission and recognition by regenerating axons

enlargement of muscle fibers which Ý synthesis of contractile proteins such as myosin

nerve section demonstrates importance of motorneuron in target maintenance

electrical alterations: resting potential Ý 15mV and change in ion channelsÞ tetrodotoxin unable to block action potential

also spontaneous fibrillation

Ý AchR synthesis and insertion in nonsynaptic regions of the muscle fiberÞ denervaton super sensitivity to NT

Cellular mechanisms of trophic Neural Influences – nerve controls target by regulating transcription via:

(1) release of trophic factors: (non-NT molecules including agrin and proteins like CGRP) – bind to receptors and initiate signaling cascades

electrical stimulation of denervated muscle result in:

return of E_r to normal
reversal of supersensitivity to NT due to termination of receptor synthesis by non synaptic nuclei
myosin synthesis increases and muscle fiber diameter becomes normal

release of nerve terminal substance must be responsible for Ý level of AchR and AchE by synaptic nuclei

agrin – causes AchR to aggregate under the synapse

Nerve controls specialized contractile properties of muscle – specialization into fast and slow fibers

nerve cross experiments show nerve is regulating differentiating levels of and types of myosin and metabolic enzymes

denervation followed by direct stimulation shows that different electrical stimulation patterns cause fiber differentiation
muscles contain mixes of fast and slow; however, alpha neurons connect only the same type in checkerboard pattern

fiber type clumping results from nerve regeneration which tends to result in transformation of reinervated adjacent fibers