Axoplasmic flow

Microtubules, an integral component of the cellular cy-toskeleton, consist of cytoplasmic tubes 25 nm in diameter and often of extreme length. Microtubules are necessary for the formation and function of the mitotic spindle and thus are present in all eukaryotic cells. They are also involved in the intracellular movement of endocytic and exocytic vesicles and form the major structural components of cilia and flagella. Microtubules are a major component of axons and dendrites, in which they maintain structure and participate in the axoplasmic flow of material along these neuronal processes. 

Vision loss may occur in deficiency states (thiamine or vitamin B12) or as a toxic response to certain drugs or substances (Box 22-5). In most cases one can establish that the patient has been exposed to toxins or has had some dietary deficiency. The precise pathogenesis of the atrophic process is somewhat obscure, although adenosine triphosphate formation appears to undergo a change. This change leads to a stasis of axoplasmic flow with subsequent optic disc edema, eventually resulting in axonal death. 

A primary lipidosis has been described in human optic nerves affected by amiodarone. One study has shown that intracytoplasmic inclusions may mechanically or biochemically block axoplasmic flow in large optic nerve axons, resulting in optic disc edema and hemorrhage. 

Complementary to vascular compromise and mechanically impaired axoplasmic flow, additional pathogenic mechanisms (Figures 30.3 30.4) that underlie glaucomatous optic neuropathy include excitotoxic damage from excessive retinal glutamate, peroxynitrite toxicity from increased nitric oxide synthase activity, immune-media ted nerve damage, and oxidative stress (Naskar and Dreyer, 2001). 

The tachykinins are a family of small peptides (fewer than 50 residues), each of which has the same amino acid sequence, Phe-X-Gly-Leu-Met-NH2, at the amidated carboxy terminus (Fig. 7.1). Although three primary mammahan tachykinins - substance P, neurokinin A (NkA) and neurokinin B (NkB) - have been recognized, only substance P and NkA have been identified in the lungs and airways. Tachykinins are synthesized in nerve cell bodies, appropriately processed, and then transported by axoplasmic flow to the terminal ramifications of axon dendrites, where they serve their neurotransmitter functions. Both substance P and NkA are derived from transcription and translation of the preprotachykinin I (PPT-I) gene (Nawa et al., 1984 Krause etal., 1987). NkB is derived from a separate gene. 

VIP is synthesized in nerve cell bodies and transported by axoplasmic flow to nerve terminals ganglia containing VIP reactive cell bodies are found in great profusion in the walls of the trachea and major bronchi (Uddman et al., 1978 Dey et al., 1981). Nerves with VIP immunoreactivity have been found in the airways of most mammalian species studied (Springall etal., 1988 Barnes etal., 1991). This immunoreactivity is localized both to nerves and to nglia in the airway wall VIP-containing neurons in the airway predominantly innervate bronchial... 

The other major toxic effect of methanol is the ocular toxicity Although formaldehyde might be formed locally in the retina, this seems unlikely, whereas formate is known to cause experimental ocular toxicity. The mechanism suggested involves inhibition by formate of cytochrome oxidase in the optic nerve. As the optic nerve cells have few mitochondria they are very susceptible to this histotoxic hypoxia . The inhibition will result in a decrease in ATP and hence disruption of optic nerve function. Thus, stasis of axoplasmic flow, axonal swelling, optic disc oedema and loss of function occur. Studies have shown that formate alone will cause toxicity in the absence of acidosis, although this will... 

Lubinska, L. (1982) Patterns of Wallerian degeneration of myelinated fibers in short and long peripheral stumps and in isolated segments of rat phrenic nerve. Interpretation of the role of axoplasmic flow of the trophic factor. Brain Res. 233 227-240. 

Interruption of axoplasmic flow axonal demyelinatlon Cell body damage in brain and spinal cord Progressive ataxia and paralysis of lower limbs. 

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