Around the time of birth, and for variable periods afterward, the latter stages of the process may still be extant, particularly in the cerebellar cortex and paravertebral ganglia. Discrimination between those that will survive and those that are effete will depend on the transfer of trophic factors between cells, including from glia to neurons. As large numbers of developing neurons are superfluous, there is a need to select amongst them and eliminate the excess by apoptosis.
The selective effects of tetanus and botulinum toxins are good examples.ĭuring organogenesis, vast numbers of neuroblasts proliferate, and immature neurons migrate to their final destinations. It is useful also to realize that neurons are extremely diverse pharmacologically and biochemically this is well illustrated by the highly selective and regionalized effects of different toxins and metabolic disturbances. This process is called trans-synaptic degeneration, and it will progress along specific anatomic pathways. If a neuron dies, surviving neurons with which it has synaptic connections may regress because of lack of activation, undergo atrophy, and eventually die. The vitality of individual neurons is sustained by their active relationship with other neurons, or other types of cells with which they interact. These issues will be addressed more fully later, under Neurodegenerative diseases. However, long lengths of the axon may degenerate without compromising the viability of the remainder of the cell and without inducing dramatic morphologic change in the soma, and there is often scope for adequate regeneration of the lost axonal extremity. Equally, when a neuron is fatally damaged, the whole cell dies, and the consequent changes will spread over the whole extent of its domain. Should the operations of the soma or the transport systems be impaired, the health of the axon will suffer and, appropriately, in most instances the largest and longest axons are most vulnerable. Neurofilaments, neurotubules, and some soluble proteins move by slow transport in the anterograde direction only, at a rate of about 1-3 mm/day, and are degraded when they reach the terminus. Mitochondria are also moved by fast transport, but at a somewhat slower rate. Larger vesicles of about 500 nm are transported retrograde by this fast pathway, and the translocator is an isoform of dynein, the ATPase that powers cilia and flagella in other types of cell. The motor for this system, intimately associated with the neurotubules, is an ATPase called kinesin. Many components are moved in the anterograde direction within 25-nm vesicles by a “fast” transport system at a rate of 20-30 mm/hr. The transport mechanisms are fuelled by the consumption of energy along the course of the axon.
The axons are serviced throughout their length by a bidirectional transport system that moves components both away from and toward the soma (anterograde and retrograde transport, respectively). The soma is the metabolic factory for the whole cell, and the great bulk of synthetic and degradative operations take place there. Also, neurons function in hierarchical chains organized into anatomic systems. Pathologic reactions within one cell may therefore be separated by considerable distance.
If the soma were enlarged to the size of an orange, the processes would have the dimensions of a garden hose and would be >20 km in length. For example, in a lumbar dorsal root ganglion of a horse, the cell body of a sensory neuron may project a process distally to the extremity of the hind foot and centrally to the caudal brainstem, making it without doubt the largest cell in the body. The whole cell constitutes a structure concerned with the generation, conduction, and transmission of impulses, and in some cases, a single cell performs this task over a very long distance. For the purposes of comprehending pathogenetic mechanisms, it is important to remember always that the neuron comprises both the cell body (“soma” or “perikaryon”) and the cell processes, in particular the axon. In conventional histopathology, the term “neuron” refers to the cell body of the nerve cell that often is only a small part of the total cell volume. The neuron is the fundamental cell of the nervous system, and ultimately all neurologic disease must involve functional disturbances in neurons.
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