Table Of ContentCONTRIBUTORS TO THIS VOLUME
JAN CAMMERMEYER MICHAEL F. SHEFF
MARTIN G. NETSKY SAMRUAY SHUANGSHOTI
J. H. QUASTEL A. EARL WALKER
SUMNER I. ZACKS
ADVISORY BOARD
M. H. APRISON FRED A. METTLER
The Institute of Psychiatric Research and Departments of Anatomy and Neurology
Department of Biochemistry Columbia University College of
Indiana University Medical Center Physicians and Surgeons
Indianapolis, Indiana New York, New York
WILLIAM ADELMAN 1. J. KOPIN
Department of Physiology Laboratory of Clinical Science
University of Maryland National Institute of Mental Health
School of Medicine Bethesda, Maryland
Baltimore, Maryland
AMEDEO MARRAZZI EZIO GIACOBINI
Department of Pharmacology Department of Pharmacology
University of Minnesota Karolinska Institut et
Medical School Stockholm, Sweden
Minneapolis, Minnesota
THOMAS W. MITTAG GERTRUDE MAENGWYN-DAVIES
Department of Pharmacology Department of Pharmacology
New York Medical College Georgetown University
New York, New York School of Medicine
Washington, D.C.
NEUROSCIENCES RESEARCH
EDITED BY
S. EHRENPREIS
DEPARTMENT OF PHARMACOLOGY
NEW YORK MEDICAL COLLEGE
FLOWER AND FIFTH AVENUE HOSPITALS
NEW YORK, NEW YORK
OTHMAR C. SOLNITZKY
DEPARTMENT OF ANATOMY
GEORGETOWN UNIVERSITY
SCHOOL OF MEDICINE
WASHINGTON, D.C.
Volume 3
1970
ACADEMIC PRESS New York and London
COPYRIGHT © 1970, BY ACADEMIC PRESS, INC.
ALL RIGHTS RESERVED
NO PART OF THIS BOOK MAY BE REPRODUCED IN ANY FORM,
BY PHOTOSTAT, MICROFILM, RETREIVAL SYSTEM, OR ANY
OTHER MEANS, WITHOUT WRITTEN PERMISSION FROM
THE PUBLISHERS.
ACADEMIC PRESS, INC.
Ill Fifth Avenue, New York, New York 10003
United Kingdom Edition published by
ACADEMIC PRESS, INC. (LONDON) LTD.
Berkeley Square House, London WIX 6BA
LIBRARY OF CONGRESS CATALOG CARD NUMBER: 68-23474
PRINTED IN THE UNITED STATES OF AMERICA
LIST OF CONTRIBUTORS
JAN CAMMERMEYER, Section on Experimental Neuropathology,
Laboratory of Neuropathology and Neuroanatomical Sciences,
National Institute of Neurological Diseases and Stroke, National
Institutes of Health, Public Health Service, U.S. Department of
Health, Education and Welfare, Bethesda, Maryland
MARTIN G. NETSKY, Department of Pathology, University of
Virginia School of Medicine, Charlottesville, Virginia
J. H. QUASTEL, Neurochemistry Section, Kinsmen Laboratories,
University of British Columbia, Vancouver, Canada
MICHAEL F. SHEFF, Department of Pathology, University of
Pennsylvania School of Medicine, Philadelphia, Pennsylvania
SAMRUAY SHUANGSHOTI, Department of Pathology, Chulalong-
kom University, Bangkok, Thailand
A. EARL WALKER, Division of Neurological Surgery, The Johns
Hopkins University, School of Medicine, Baltimore, Maryland
SUMNER L ZACKS, Ayer Clinical Laboratory, Pennsylvania Hospital
and Department of Pathology, University of Pennsylvania School
of Medicine, Philadelphia, Pennsylvania
PREFACE
Volume 3 of Neurosciences Research differs from the first two vol
umes in that emphasis is almost exclusively on research problems
concerned with the central nervous system. In accordance with our
previous concepts, the discussions are, for the most part, of a broad
interdisciplinary nature, i.e., physiological, biochemical, anatomical,
and thus should be of interest for the wide spectrum of researchers,
graduate students, and clinicians working in the field of the neuro
sciences. Perhaps the one exception is the very interesting article by
A. Earl Walker on "The Role of the Cerebral Peduncle in Move
ments." The discussion is limited namely to the effect on body move
ment of partial and complete pedunculotomy. But even in this in
stance. Walker uses a varied approach to the problem of the role of
the peduncle: ablation, careful evaluation of the nature and extent
of the lesions produced, cortical stimulation to evaluate pathways
involved, and the study of afterdischarge following sectioning. The
ultimate conclusions are quite far reaching, not only in terms of the
peduncle but also for the involvement of the entire pyramidal and
extrapyramidal tracts in body movement.
Martin G. Netsky and Samruay Shuangshoti discuss in detail the
choroid plexus from the standpoints of morphology, histochemistry,
function, and pathology, with an emphasis on electron microscopic
investigation. An important function of the choroid appears to be in
relation to cerebral circulation, which is considered as "an important
source of blood in the cerebral ventricle of the newborn." Attention
is also given to the possible involvement of the choroid in certain
intraventricular hemorrhages.
The study of transport processes in the brain is becoming in
creasingly important in many investigations in the fields of neuro-
chemistry and neurophysiology. The manner and extent of transfer
of nutrients, salts, vitamins, or drugs across the membranes of brain
cells are basic to our understanding of the events taking place in the
living brain. The article by J. H. Quastel provides a survey of present
knowledge on transport processes and supplies extensive documen
tation so that the reader may pursue the subject further.
In a richly illustrated light microscopic study on microglia, Jan
Cammermeyer arrives at the conclusion that microglial cells should
viii Preface
be regarded as inherent elements of the central nervous system be
cause of their ubiquitous presence in mammals, including germfree
animals, and in immature tissue as well as in fully developed tissue
from birth to old age. On the basis of a review of experimental material
in which numerous mitotic cells occur, he presents microscopic evi
dence of the ability of microglial cells to enter into mitosis and of
their development from mitotic cells. By determining the post
operative incidence of mitosis, he has been able to clarify regional,
species, and age factors that may influence the onset of microglial
cell proliferation at various sites outside and within the vascular
wall. His observation that a larger number of mitotic cells undergo
degenerative changes as a need for microglial cells decreases is
ascribed to a mechanism whereby completion of mitosis can be inter
rupted and overpopulation of microglial cells avoided.
Sumner I. Zacks and Michael F. SheflF discuss the mechanism of
tetanus intoxication, considering it as a biological phenomenon in
which a very small amount of foreign protein produces a profound
neuromuscular disturbance. They use a multidisciplinary approach
emphasizing direct positive evidence from physiological, biochemi
cal, and electron microscopic studies to discuss the various hypothe
ses which have been developed to explain the potency of the toxin
and the course of the intoxication. Thev conclude that the toxin acts
in both skeletal muscle and the central nervous system where it af
fects some critical step in ion transport that is expressed as hyper-
irritability of both sites.
The editors once again wish to thank the staff of Academic Press
for its assistance in expediting the rapid publication of this volume
of Neurosciences Research.
CONTENTS OF PREVIOUS VOLUMES
VOLUME 1
Chemical Studies on Individual Neurons
Part 1. Vertebrate Nerves
EZIO ClACOBINI
Chemical Correlates of Neural Function
CEORGES UNGAR AND LOUIS N. IRW^IN
A Combined Neurochemical and Neurophysiological
Approach to Identification of Central Nervous
System Transmitters
M. H. APRISON AND R. WERMAN
Muscular Tone and Movement: Their Cerebral Control
in Primates
FRED A. METTLER
Neural Mechanism Controlling Skeletal Muscular
Activity and Its Unsolved Problems
PAUL C. BUCY
Psychophysics of Excitation and Tranquilization from a
Steady-State Perspective
ROLAND FISCHER AND MARSHA A. ROCKEY
Learning and Use of Knowledge
JACQUES BARBIZET
High Speed Techniques in Biological Research and Their
Utilization in Experimental Head Injury
E. S. GURDJIAN, V. R. HODGSON, L. M. THOMAS, AND L. M. PATRICK
Author Index Subject Index
xii Contents of Previous Volumes
VOLUME 2
Calcium and the Excitable Cell Membrane
K. KOKETSU
Calcium-Adenosine Triphosphate-Lipid Interactions and Their
Significance in the Excitatory Membrane
L. G. ABOOD
Intracellular Perfusion of Squid Giant Axons: Recent Findings
and Interpretations
L. LERMAN, a. WATANABE, AND L TASAKI
Chemical Studies on Individual Neurons. Part II. Invertebrate
Nerve Cells
Ezio GIACOBINI
Response Augmentation and Blockade in Cholinergic
Neuromuscular Tissues
S. L. FRIESS
What Is the Functional Role of Central Nervous Serotonin?
WERNER P. KOELLA
General Neuropathology of Degenerative Processes of the
Nervous System
FRANZ SEITELBERGER
Sphingolipid Metabolism in Neural Tissues
RoscoE O. BRADY
Author Index-Subject Index
TRANSPORT PROCESSES AT THE
BRAIN CELL MEMBRANE
/. H. Quastel
NEUROCHEMISTRY SECTION, KINSMEN LABORATORIES, UNIVERSITY OF BRITISH
COLUMBIA, VANCOUVER, CANADA
I. The Sodium Pump 2
A. Na-K-ATPase and Cation Transport 4
B. Cation Transport and Respiratory Control of the Brain... 6
C. EfiFects of Ammonium Ions 8
D. Effects of Calcium Ions 9
E. EfiFects of Lithium Ions 10
II. Sugar Transport in the Brain 10
A. Hexoses 10
B. Pentoses 12
C. D-Glucosamineand 2 Deoxy-D-glucose 13
D. Insulin and Carbohydrate Uptake in the Brain 13
III. Transport of Amino Acids in the Brain 14
A. Transport in Vivo 14
B. Transport in Vitro 17
IV. Transport of Amines in the Brain 25
A. Choline 25
B. Acetylcholine 26
C. Serotonin 26
D. Action of Reserpine 27
E. Catecholamines 28
F. Creatine 30
G. Thiamine 30
V. Transport of Anions in the Brain 30
A. Ascorbate 30
B. Acetate 31
C. Citrate 31
D. Sulfate 32
VI. Transport of Drugs into Brain 32
VII. Transport of Water in the Brain 34
References 35
2 /. Η. Quastel
I. The Sodium Pump
It is now well known that changed rates of transfer of sodium and
potassium ions through the nerve cell membrane may take place when
the energetics of the cell are aflFected, as for example during anoxia
(1, 2) or in the presence of cyanide (3) or of 2,4-dinitrophenol. In fact,
metabolic energy is required for the operation of the mechanisms that
are responsible for maintaining the relatively high internal potassium
ion concentration and low sodium ion concentration characteristic
of the nerve cell (4). The energy-dependent process by which sodium
is extruded from the cell against a concentration gradient is usually
referred to as the sodium pump. Experiments (5) carried out with
squid axons, by injection of radioactive sodium ions, have shown that
administration of cyanide, dinitrophenol, or azide reduces the efflux
of radioactive sodium ions from Üie axon, the rate of decline being
parallel to the fall in the amount of high energy phosphate present.
Injection of ATP (adenosine triphosphate) into the poisoned axon
brings about an increased sodium efflux, the amount depending on the
quantity of ATP injected.
The complete removal of potassium ions from the external medium
reduces the efflux of sodium ions from the nerve fiber while increas
ing the concentration of potassium ions in the medium increases the
sodium ion efflux. Mammalian cerebral slices concentrate potassium
ions from the external medium during incubation at 37° (following the
initial rapid loss taking place when they are placed in the medium).
The concentration of potassium ions is diminished in the absence of
oxygen or of glucose (6, 7).
The levels of transmembrane potentials are related to the potassium
gradients across the cell membrane in brain slices as they are in other
excitable tissues (8, 9).
Asymmetry in the movements of potassium and sodium during
activity of the sodium pump results in a difference of potential across
the membrane (10, 11), and electrogenesis, due to the sodium pump,
is observed in a variety of tissues, such as frog muscle fibers (12) and
molluscan neurons (13, 14).
The energy-dependent uptake of potassium ions into the brain cell
is sodium dependent (15, 16) and indeed the presence of sodium ions
is essential for various phenomena in brain tissue that are brought
about by increased potassium ion concentrations in the medium sur
rounding the brain, e.g., stimulated respiration (17), stimulated phos
phate incorporation into phosphoproteins (18) or phospholipids (19),
and stimulated synthesis of acetylcholine (20).
