Brain Biochemistry

72 Pages·1974·5.508 MB·English

by  H. S. Bachelard (auth.)

Brein Biochemistry
Other titles in the senes
Biochemical Genetics R.A. Woods
Cell Differentiation J .M. Ashworth
Cellular Development D.R. Garrod
Functions of Biological Membranes M. Davies
Immunochemistry M.W. Steward
Molecular Virology D.A. Ritchie, T.H. Pennington
Biochemical Pharmacology B.A. Callingham
OUTLINE STUDIES IN BIOLOGY
Editors: Professor T.W. Goodwin, F.R.S., University of Liverpool
Professor J.M. Ashworth, University of Essex
Editors' Foreword
The student of biological science in his final years as an undergraduate and his first years as a
postgraduate is expected to gain some familiarity with current research at the fron tiers ofhis
discipline. New research work is published in a perplexing diversity of publications and is inevi
tably concemed with the minutiae of the subject. The sheer number of research journals and
papers also causes confusion and difficulties of assimilation. Review articles usually presuppose
a background knowledge of the field and are inevitably rather restricted in scope. There is thus
the need for short but authoritative introductions to those areas of modem biological research
which are either not dealt with in standard introductory textbooks or are not dealt with in suf
ficient detail to enable the student to go on from them to read scholarly reviews with profit. This
series of books is designed to satisfy this need.
The authors have been asked to produce abrief outline of their subject assuming that their
readers will have read and remembered much of a standard introductory textbook of biology.
This outline then sets out to provide by building on this basis, the conceptual framework within
which modem research work is progressing and aims to give the reader an indication of the
problems, both conceptual and practical, which must be overcome if progress is to be main-
tained. We hope that students will go on to read the more detailed reviews and articles to which
reference is made with a greater insight and interstanding of how they fit into the overall scheme
of modem research effort and may thus be helped to choose where to make their own contribution
to this effort.
These books are guidebooks, not textbooks. Modem research pays scant regard for the aca
demic divisions into which biological teaching and introductory textbooks must, to a certain
extent, be divided. We have thus concentrated in this series on providing guides to those areas
which fall between, or which involve, several different academic disciplines. It is here that the
gap between the textbook and the research paper is widest and where the need for guidance is
greatest. In so doing we hope to have extended or supplemented but not supplanted main texts,
and to have given students assistance in seeing how modem biological research is progressing,
while at the same time providing a foundation for self help in the achievement of successful
examination results.
Brein Biochemistry
H.S. Bachelard
Reader in Neurochemistry
Institute 01 Psychiatry, London
Springer-Science+Business Media, B.V.
© 1974 H.S. Bachelard
Originally published by Chapman and Hall in 1974.
Typeset by E. W.c. Wilkins Ltd. • London
ISBN 978-0-412-12760-1 ISBN 978-1-4899-3392-8 (eBook)
DOI 10.1007/978-1-4899-3392-8
This paperback edition is sold subject to the condition that it shall not,
by way of trade or otherwise, be lent, re-sold, hired out, or otherwise
circulated without the publisher's prior eonsent in any form of binding
or cover other than that in which it is published and without a similar
condition including this condition being imposed on the subsequent
purchaser.
All rights reserved. No part of this book may be reprinted, or repro
duced or utilized in any form or by any eleetronic, mechanical or other
means, now known or hereafter invented, including photocopying and
recording, or in any information storage and retrieval system, without
permission in writing from the Publisher.
Distributed in the U.S.A.
by Halsted Press, a Division
of John Wiley & Sons, Ine. New York
Ubrary of Congress Catalog Card Number 74-4105
Contents
1 Introduction page 7
References 8
2 Appearance of the brain 9
2.1 Gross appearance 9
2.2 Fluid compartments 9
2.3 Microscopic appearance 12
2.3.1 Neurones 13
2.3.2 Glial cells 14
2.3.3 The synapse 15
References 17
3 Neurotransmission 18
3.1 The resting potential 18
3.2 The sodium pump 19
3.3 The action potential and nerve conduction 20
3.4 Chemical events at the synapse 22
3.4.1 Identification and occurrence of neurotransmitters 23
3.4.2 The quantum hypothesis 28
3.4.3 Metabolism of acetylcholine 30
3.4.4 Catecholamines: noradrenaline and dopamine 31
3.4.5 5-Hydroxytryptamine 34
3.4.6 Breakdown of the biogenic amines 34
3.5 Origin of synaptic vesicles 34
3.6 Post-synaptic events 35
3.6.1 Involvement of cyclic AMP 37
3.6.2 Receptors 40
3.7 Neurone-axonal transport 41
3.7.1 Mechanism oftransport in axoplasmic flow 43
3.7.2 Axonal pro tein synthesis 43
References 44
4 Adaptive processes in the brain 47
4.1 Inducible enzymes 47
4.1.1 Adaption to specific substrates 49
4.1.2 Adaption to the product of an alternate pathway 53
4.1.3 Adaption involving coenzyme 54
4.1.4 Adaption in response to hormones 54
4.2 Adaption to the environment 55
4.2.1 light 55
4.2.2 The pineal gland 58
4.3 Drug tolerance and dependence 59
4.3.1 Morphine 60
4.3.2 Amphetamines 62
4.3.3 Ethanol 63
4.4 Learning and memory as adaptive processes? 65
References 66
Index 68
1 Introduction
The brain is the most complex and highly of semi-permeable excitable membranes which
specialised of all mammalian organs. Under can be caused, rapidly and transiently, to under
standing the complexity of its function remains go changes in permeability to small chemical
man's greatest challenge. The functional unit is molecules and to cations. The highly specialised
the neurone, or excitable nerve cell, making ana nature of the constituent cells, with their unique
tomical and chemical connections with other function and specificity, is c10sely related to
units in the system. Many of the essential bio the structure of the whole tissue. The underlying
chemical connections of the nerve cell are de chemical processes cannot be discussed or seen
pendent upon special morphological features: in perspective without constant awareness of
synaptic contact is mediated by chemical mol related aspects of physiology and morphology.
ecules, 'neuro-transmitters' which ensure the The hrain is structurally extraordinarily com
continued propagation of electrical impulses plex in its distinct anatomical regions, each of
through sequential units of the system. Also which is heterogeneous in the types and struc
c10sely related to the morphology of the ner tures of the constituent cells.
vous system is the chemical energy expended in One aspect of the biochemical function of
maintaining distribution gradients of cations the brain can be seen in its efficient production
across cellular membranes. Chemical neuro of the energy required to support the unique pro
transmission results in an alteration in cation cesses referred to above. This energy, essentially
distribution and while the energy-utilising mech stored as ATP, is produced from the oxidation
anisms which underly their redistribution are of glucose by mechanisms common to all bio
not peculiar to the nervous system, they are of logical cells. The importance in the brain of
particular importance to neural function. The these processis is quantitative, rather than
mechanisms of chemical transmission, in con qualitative. The brain depends absolutely for its
trast, are peculiar to the nervous system. ability to function normallyon a constant
Nerve cells are unique in their ability to supply of glucose and oxygen from the blood
trigger off and maintain conduction of elec stream. It has virtually no reserves of chemical
trical impulses over long distances, which may energy, compared with other tissues and organs.
be measured in metres, without significant loss Stored concentrations of glucose and glycogen
of strength of the conducted impulse. Remark (each of the order of 1-2 Ilmoles/g) and of
able also is the specificity of their connections, ATP (3 Ilmoles/g) are sufficient to maintain
not only with other nerve cells, but also with function in isolation for minutes only, if per
non-neural target cells in sites such as the endo manent damage is not to ensue and under nor
crine glands or musc1es. mal circumstances, the brain cannot utilise
These unique features rest in the possession alternative sources for its energy
7
requirements [I]. The importance of the con progressive improvement in their environment [3] .
stant blood supply of essential nutrients can be Further indications of the sensitivity of the
readily appreciated if we remember that this brain to general metabolie impairment arise
organ, only some 2% of the total adult body from the high proportion of inherited metabolie
weight, consumes some 20% of the glucose disorders which result in mental disturbance or
required by the whole body. This supply is in retardation so important in Neurology and
fact supported by the blood: one-fifth ofthe Psychiatry[4, 5] ;
output of the heart passes through the brain. To be able to understand what he is trying to
The brain is therefore the most sensitive part of achieve, the biochemist who studies brain func
the body to failure in oxygen or glucose. In the tion must acquaint hirnselfwith related aspects
absence of either of these, fainting occurs of morphology, physiology and pharmacology;
within seconds, and if not corrected, coma and the chemical function of the brain cannot be
death follow rapidly. It is usually the first organ separated from the architectural integrity of the
to suffer. Its peculiar sensitivity to abnormalities cellular relationships. For a small book of this
in energy metabolism can also be seen in the type the topics selected concentrate on the
features of vitamin deficiency, especially of chemical events related to excitability and trans
those vitamins such as the B group which func mission and to the adaptability of the brain to
tion as coenzymes in intermediary energy met react to various stimuli both from within and
abolism. Although any deficiency affects the without the body. To this end, abrief descrip
same metabolie pathways in the same way tion of the associated morphology and physiol
throughout the body, one of the most profound ogy seems an essential requirement and is treated
consequences is impaired mental function and first. Then follows a description of membrane
in children, often mental retardation. It must be permeability phenomena and neurotransmission.
stressed that this is due, not to specialised The fmal seetion of the book is concemed with
qualitative metabolism by the brain, but to its aspects of the chemical response of the brain to
very high sensitivity to any impairment in the its immediate environment and as a result of
normal processes of energy production. hormonal signals reaching the brain.
This is of particular importance in the
nutrition of the underdeveloped 'third world', References
where deficiency or dietary imbalance may [1] McIlwain, H. and Bachelard, H.S. (1971),
cause irreparable mental damage to the de Biochemistry and the Central Nervous System
veloping child, and which has been the concern (4th ed.), Churchill, London.
of special symposia [2] . Not only is an inad [2] CIBA Foundation Symposium (1972),
equate environment increasingly suspected of Lipids, Malnutrition and the Developing
leading to impaired intelligence in the poorer Brain, Elsevier, Amsterdam.
parts of the world, hut evidence is also to hand [3] Scottish Council for Research in Education
that this can be seen in countries normally re (1949), The Trend ofS cottish Intelligence
garded as rich and developed. Although current London University Press, London.
discussions on the relative influences of heredity [4] Cumings, J.N. and Kremer, M. (1968),
and of environment on the development of Biochemical Aspects ofN eurological Dis
intelligence are heated and controversial, studies orders (3rd Series), Blackwell, Oxford.
such as those on Scottish children over aIS [5] Cumings, J.N. (1972), (ed.) Biochemical
year period indicate that a consistent if small Aspects ofN ervous Diseases, Plenum,
increase in intelligence can result from London.
8
2 Appearance of the brain
2.1 Gross appearance. emotion [2] , are phylogenetically older, and
Biochemists tend to study the brains of small have changed little in relative size, as the
mammals and consciously or subconsciously shaded areas show [3,4]. For the non
extrapolate to what might occur in the human anatomically trained, the nomenclature of the
brain, itself subject to obvious limitations in regions and specialised parts of an organ as com
opportunities for chemical exploration. Yet plex as the brain is daunting. In fact the brain
what do we mean by the 'mammalian' brain, should really be regarded as a collection of
since the brain of a rat or guinea pig is obviously highly specialised organs rather than as a single
far different in appearance and many functions organ. Often various areas of the brain are cited
from that of Man? The brain has evolved and in biochemical articles as experimental material
specialised within mammalian species more than and the untutored reader may be uncertain of
any other organ ofthe body: Fig. 2.1 shows a the site and significance of the part named. The
comparison of the brains of a selected group of major areas of the human brain which are likely
mammals and it should be remembered that to be referred to are shown in Fig. 2.2 (see also
increasing size is not necessarily associated with Table 3.2 of Chapter 3). The first part of the
increased intelligence or sophistication of func illustration (a) shows the lateral aspect of the
tion. The main discernible change that has whole brain, viewed from the left hand side:
occurred during evolution of the mammalian the central drawing (b) shows some of the
brain is in the size and complexity of the cere internal parts which are seen if the brain is
bral cortex. The increase in surface area per unit divided into the two hemispheres. This is the
of volume of the cortex has been effected by right hemisphere viewed from the left hand
increased folding so that the convolutions of side. The whole brain has been divided into
the human cerebral cortex are considerably four main parts for convenience: the cerebrum,
more extensive than of the rat or rabbit. The the cerebellum, the mid-brain and the brain
function of the cortex has altered also: the stern, and it is the latter which contains a large
'primary cortex' concerned with sensorimotor number of specialised parts indicated in Fig. 2.2.
function (Fig. 2.1) has remained proportion The third illustration (c) shows the interior of
ately much the same, but the areas devoted to the brain cut horizontally and viewed from
'association', Le. areas concerned with higher above.
functions of learning and decision-taking, have
increased considerably [l] . 2.2 Fluid compartments.
Other areas, such as the limbic system (Fig. One prominent feature of the gross anatomy of
2.1), concerned with more primitive functions the brain is its extensive blood supply - perhaps
of homeostasis, motivation and especially not surprisingly, since it uses about one-fifth of
9