Axoplasmic Transport

Zafar Iqbal

• Publisher: CRC Press
• Year: 2018
• Print ISBN: 9781315890906
• eBook ISBN: 9781351086905
• Topic: Biological Sciences
• Subtopic: Biology
• Index: Biological Sciences

Axoplasmic transport is the intracellular movement of cellular components required for the maintenance and normal physiological functioning of neuronal cells. This book provides an up to date reference for both established investigators as well as for those entering in the field.This volume describes the history and methods of the study of transport and the involvement of energy, ions, calmodulin, microtubules and other cellular components in transport. It also discusses the transport of polypeptides, lipids, nucleic acids, neutrotransmitter containing components and various other particles in nerve fibres. A significant portion of this book is devoted to axoplasmic transport, regeneration and the relevance of transport in neurotropic functions are described in the alst four chapters, followed by a discussion on the mechanism of axoplasmic transport.

Chapter 1

A BRIEF HISTORICAL INTRODUCTION TO AXOPLASMIC TRANSPORT

Sidney Ochs

TABLE OF CONTENTS

I.	Development of the Concept of Transport in Nerve
	A.	The Older Conception of Nerve Function
	B.	Nerve Form and Material Transport
	C.	Cell Body-Fiber Dependence
	D.	Fibrillary Elements within the Fibers — Cytoskeleton
	E.	Damming and Fluid Outflow as Evidence of Transport
	F.	Tracer Techniques, Enzymes, and Optical Methods
References

I. DEVELOPMENT OF THE CONCEPT OF TRANSPORT IN NERVE

A. The Older Conception of Nerve Function

The idea of a spirit-like influence flowing in nerve can be traced back to ancient Greek physiological speculation. As later formulated by Galen in the 2nd century, a spirit-like principle is inhaled during inspiration and carried by the blood to the brain where an animal (animating) spirit is abstracted into the ventricles of the brain. The animal spirit then moves down within the hollow nerves to effect motion and sensation. The hollow nerve concept was an extrapolation from what appeared to be the case in the bovine optic nerve.¹ This was an extraordinarily long-lasting concept with traces of it seen lingering even into the 19th century.² In the mechanistic twist given to Galen’s theory by Descartes in the 17th century,³ the animal spirits, were viewed as the” liveliest and subtlest” of particles. To explain reflex action the animal spirits are able to leave the ventricles when flaps within the individual nerve fibers are pulled on by sensory stimulation. Under control of the pineal, the animal spirits then flow from the ventricles of the brain down within the opened individual hollow nerve fiber into their muscles to inflate them and thus cause the body to move in an appropriate fashion.

An inflation of muscle by animal spirits or a nerve fluid was disproved by the plethysmographic studies of Swammerdam soon after Descartes’ formulation. Using the isolated frog muscle preparation, Swammerdam in the 17th century found on stimulation of its nerve that there was no increase in muscle volume during contraction. Similar plethysmographic studies made by Steno and Glisson at this time using the human arm also showed the lack of an increased muscle volume on contraction.^4,5

In the 17th and 18th centuries various theories were advanced to account for nerve and muscle action with most retaining the concept of nerves consisting of hollow tubes with a nerve fluid of some kind moving down inside them. In one theory the nerve substance was considered to bring about an explosive reaction in the muscle to account for its contraction. There were also more physical conceptions of nerve action, with the nerve fibers transmitting some kind of a vibratory influence, either like sound waves or as a vibration of ether within the fibers.⁶

When electricity came under renewed scientific study in the late 18th century, it was usually dealt with as a flow of one or more fluids. Galvani⁷ conceived of the animal electricity produced in the body as a fluid of a lively and peculiar kind which he assimilated to the old idea of a nerve spirit or fluid moving down within hollow nerve tubes. He wrote that,” the electric fluid is produced by the activity of the cerebrum, that it is extracted in all probability from the blood and that it enters the nerves and circulates within them in the event that they are hollow and empty or, as seems more likely, they are carriers for a very fine lymph or other similarly subtle fluid which is secreted from the cortical substance of the brain, as many believe. If this be the case, perhaps at last the nature of animal spirits, which has been hidden and vainly sought after for so long will be brought to light with clarity”.

B. Nerve Form and Material Transport

The concept of a nerve fluid had been given substantiation by the early microscopic studies of Van Leeuwenhoek⁸ as described in a letter written in 1717. When he placed freshly cut cross-sections of bovine optic nerve under his simple microscopes the nerve fibers were seen to be circular. Within a minute or so, a pearly fluid exudate appeared over the center of each of the circular cross-sections to form a little mound. This soon passed off as a vapor with the fibers collapsing to form flattened bands. Van Leeuwenhoek concluded that normally the nerve fluid within the fibers distends the walls of the nerve tubes, causing them to assume a cylindrical form and on cutting the nerves the escape of the nerve fluid allows the pressure on the walls to decrease and the fibers to collapse.

Chromatic and other optical distortions inherent in the lenses then used for microscopy made studies at higher magnification difficult until the achromatic compound lens microscope became available in the early part of the 19th century. With such a microscope Ehrenberg⁹ in the 1830s clearly pictured the individual fibers. However, because he separated nerve fibers by compressing the entire nerve under microscopic control,¹⁰ the fibers assumed an abnormal beaded shape which led to their confusion with nerve cell bodies. Purkinje and Valentin soon thereafter identified the nerve cell body by the presence of the nucleus.^11,12 Unfortunately, from their microscopical studies, these pioneers considered the nerve cell bodies and fibers to be two separate and distinct neural entities.^2,13 The cell body was considered to be the active element which in some fashion causes the nerve fluid contained in the apposed nerve fibers, the passive element, to circulate.^14,15 The fibers were viewed as closed loops with their central ends apposed to the cell bodies in the ganglia or in the central nervous system, their peripheral ends acting as sensory endings or contacting muscles to cause them to contract. This concept of a circulation of nerve fluid in looped fibers could have been influenced by some earlier hypotheses made of a circulation of nerve fluid in nerve fibers¹⁶ inspired by Harvey’s demonstration of the circulation of blood.

C. Cell Body-Fiber Dependence

Remak in an early paper in 1838 and definitively in his thesis 2 years later,¹⁷ was the first to advance the idea that the nerve fibers and cell bodies constitute a single neural entity, i.e., to espouse an “early neuron doctrine”.^2,18 Remak wrote that,” the organic fibers originate from the substance of the nucleated globules itself. In spite of the fact that this observation is very difficult and requires great dexterity in preparation as well as in observation, it is so well founded that it already would not be possible to doubt (it)”.¹⁹ This early conception of the neuron as an entity was in direct opposition to the dual neural element concept of Valentin and Purkinje and led to a long and dogged dispute between Remak and Valentin.¹⁹ Only late in the 19th century, with the work of His,²⁰ Forel,²¹ and Ramon y Cajal^22,23 among others, did the evidence for a single neuron element become massive and convincing and in Waldeyer’s review,²⁴ the concept became formally baptized as the neuron doctrine. Finally, the outgrowth of fibers from cells shown directly in the tissue culture studies of Harrison²⁵ served to remove lingering reservations even as late as 1910 concerning the neuron doctrine.²⁶

In spite of the uncertain status of the true nature of the neuron in the mid-19th century, Waller²⁷ inferred from his experiments on nerve degeneration that the viability of the nerve fiber depends on its connection with the cell body. He considered that some trophic influence passes from the cell body into the fiber to maintain its viability. This was clearly indicated in a classic study where the roots and nerves of the 2nd cervical ganglia of kittens were separately transected and those portions of the fibers of the nerves or roots connected to the dorsal root ganglion were seen to retain their normal form, while the part of the fiber separated from the ganglion underwent degeneration. Waller²⁸ concluded that,” the ganglion corpuscles (cell bodies) present in the dorsal root ganglion exert a trophic influence necessary to maintain the form and function of the fibers ascending in the dorsal root fibers as well as on the sensory fibers descending in the peripheral nerve”. And,” as long as the influence of the ganglion over the nerve fiber occurs, this equilibrium (forces of renewal as opposed to those of degeneration) is maintained, but as soon as the connection of the ganglion corpuscle with the nerve fiber is destroyed, its peripheral (severed) end … is subjected to forces of destruction (degeneration)”. Waller²⁹ later figuratively put it that” a ganglion therefore was to the fibers connected to it what a river was to the rivulet that trickled from it, a source of nutritive energy”.

D. Fibrillary Elements Within the Fibers — Cytoskeleton

The presence of a nerve fluid capable of moving in hollow nerve fibers appeared to conflict with another of the pioneer observations made by Remak,³⁰ namely that a fibrilla...

Table of contents

• Cover
• Title Page
• Copyright Page
• Dedication
• Table of Contents
• Chapter 1 A Brief Historical Introduction to Axoplasmic Transport
• Chapter 2 Analytical Techniques for the Study of Axoplasmic Transport
• Chapter 3 Prelude to Fast Axonal Transport: Sequence of Events in the Cell Body
• Chapter 4 Ionic Requirements for Fast Axonal Transport
• Chapter 5 Calmodulin and Its Role in Axoplasmic Transport
• Chapter 6 Metabolic and Ionic Properties of Axoplasmic Transport in Relation to its Mechanism
• Chapter 7 Intra-Axonal Transport of Cytoskeletal Proteins
• Chapter 8 Nucleic Acid Transport
• Chapter 9 Axonal Transport of Glycoproteins and Proteoglycans
• Chapter 10 Particle Movements in Axoplasmic Transport
• Chapter 11 Axonal Transport of Neurotransmitter Organelles in Adrenergic, Cholinergic, and Peptidergic Neurons
• Chapter 12 Axonal Transport in Nerve and Muscle Diseases
• Chapter 13 Axonal Transport in Experimental Diabetes and Other Models of Metabolic and Toxic Neuropathies
• Chapter 14 Axoplasmic Transport of Neuropeptides in Pathological Systems
• Chapter 15 Chemical Neurotoxins and Disruption of the Axonal Transport System
• Chapter 16 The Relevance of Axoplasmic Transport in Neurotrophic Functions
• Chapter 17 Regeneration Studies in Relation to Transport
• Chapter 18 Retrograde Transport and Regeneration Studies
• Chapter 19 The Destination and Modification of Fast-Transported Proteins in Normal and Regrowing Nerve
• Chapter 20 The Mechanism of Axoplasmic Transport
• Index