Neurochemistry of Depression

There is little doubt that a neurotransmitter imbalance is associated with both types of endogenous and exogenous depression. Noradrenaline, dopamine, serotonin and acetylcholine are all probably implicated in one way or another. The evidence for this belief comes mainly from neuro-pharmacology (Figure 21.5). Agents that deplete monoamines such as reser-pine (see Chapter 16) tend to induce depressive illness whilst agents that have the opposite effect, most importantly the MAO inhibitors...

Cells Of The Nervous System

Where Optic Nerve Brain

The nervous system is built of two major types of cell neurons and neuroglia ( glia). Both play essential roles in the life of the system. It is only the neurons, however, that are able to transmit messages from one part of the CNS to another or out of the system altogether to the muscles and glands, and vice versa from the sense organs into the CNS. Let us consider each type of cell in turn. Neurons constitute some of the most interesting and intensively studied of all the cells in the body....

Fragile X Syndrome FraX

Fragile X syndrome is, after Down's syndrome, the commonest inherited mental deficiency. It develops in one in every 2000 males and one in every 4000 females. In addition to low intelligence, it is often associated with autistic behaviour patterns. As its name indicates, it is due to a deficiency on the X chromosome. This is why it is twice as prevalent in males as in females. One of the intriguing features of the syndrome is that its severity tends to increase and its time of onset decrease...

Drosophila

The experimental approach to learning in Drosophila is rather similar to that used in C. elegans but distinctively different from that for higher organisms. Because of its small genome and the highly developed state of Drosophila genetics it is possible to search for single mutations that affect learning and then to search for the gene product involved. The publication of the complete genome sequence in March 2000 has greatly expedited this approach. The associative learning test most used with...

Pax6 Developmental Genetics Of Eyes And Olfactory Systems

This chapter has shown us the remarkable molecular commonalities underlying forms that were previously felt to be widely divergent. We should not finish without citing the fascinating work on the early development of eyes and olfactory systems which emphasises once again this unexpected commonality. The question has often been asked, when reviewing the vast variety of complex eyes developed in the animal kingdom did all these different designs arise independently, or do they share a single...

Biomembranes

Huge extent and intricacy of cerebral membrane systems. Biochemical structure lipids, proteins, carbohydrates. Lipids phospholipids - amphipathic character - bilayers and micelles - artificial bilayers and liposomes - dynamism - lipid packing and membrane fluidity. Sphingosine and its derivatives. Glycolipids cerebrosides and gangliosides - Tay-Sachs disease. Cholesterol and its function in 'stiffening' membranes. Membrane fluidity - microdomains (rafts) - caveolae. Membrane asymmetry - E- and...

Motor Neuron Disease Mnd Amyotrophic Lateral Sclerosis

MND is a generic term which covers a number of disorders that affect the motor outflow from the CNS. These include amyotrophic lateral sclerosis (ALS), often known as Lou Gehrig's disease (after the US baseball player), Kennedy's disease (X-linked spinobulbar muscular atrophy), and four types of spinal muscular atrophy. In this section we shall only consider ALS. This is by far the commonest of the motor neuron diseases, having a prevalence of Figure 21.3 Inactivation of neurofibromin affects...

Jdz

Figure 8.3 The serpentine receptor. (A) The seven transmembrane helices are shown as columns in the membrane, labelled 1-7. The N-terminal sequence is extracellular and is usually glycosylated (Ys). The extracellular loops are labelled e-1,e-2,e-3 and may also sometimes be glycosylated. The intracellular loops i-1, i-2, i-3 provide recognition surfaces for designated G-proteins. The black spots represent phosphorylation sites for PKA and the crosses represent sites for specific desensitising...

Neuronal K Channels

Biophysical and molecular biological studies have shown there to be a huge variety of neuronal potassium channels. Some are ligand-gated but the majority, to a greater or lesser extent, are sensitive to transmembrane voltage. They have many functions but one of their major roles is to stabilise the membrane potential at approximately the Nernst potassium potential (VK) (see Chapter 14). When their molecular structure was determined (see below) they were found to fall into three major groups...

Thermal Conditioning in C elegans

The structure of C. elegans' nervous systems has, so to speak, been 'run into the ground' by reconstruction from serial electron micrographs. All its neurons, their shapes, sizes and connections, have been mapped. Like many other invertebrates the neurons and their synaptic contacts are identical in isogenic animals. The genetics of the worm are also well researched and many mutants affecting the development and structure of the nervous system have been isolated. The world of C. elegans is very...

Introduction Ontogeny Recapitulates Phylogeny

Biogenetic Law

In Chapter 1, when introducing nervous systems, we noted Haeckel's well-known biogenetic law 'ontogeny recapitulates phylogeny'. Legend has it that the origins of this 'law' lie in an instance of very un-Teutonic serendipity. It is said that the labels fell off von Baer's specimen jars and he suddenly found it impossible to tell which early embryo was which. K.E. von Baer (1792-1876) was one of the founding fathers of modern embryology. Figure 18.1 illustrates his difficulty. Although this...

P

P21Ras 171, 401, 450, 451 Pacemakers 233 Pain 395-7, 397F Paired helical filaments (PHFs) see Alzheimer's disease Palindromic sequences 53, 97 defined 53 Paramecium 542 Paramytonia congenita (PC) 272 Paranode see node of Ranvier Paranoia 557 Paraquat and Parkinsonism 525 Parkinson, J. 522 Parkinson's disease (PD) 385, 393, 455, 522-6 and environment 524-5 paraquat 524, 525F rotenene 525 and basal ganglia 522, 523F festination 522 and L-DOPA 385, 524 MPP+ 524 and MPTP 524 and selegiline 524...

Prions And Prion Diseases

Prions and prion diseases have attracted much attention in recent years due to the economic significance of bovine spongiform encephalopathy (BSE) or 'mad cow disease' (MCD) and the fear that it might cross the species boundary and induce similar degenerations in humans. BSE, however, is just one example of a spectrum of neurodegenera-tive diseases ranging from Creutzfeldt-Jakob disease (CJD) in humans to scrapie in sheep (Table 21.1). The pathological signs of all these diseases include...

Info

Phenylalanine hydroxylase co-factors Many of these lesions affect other bodily systems the central nervous system (perhaps because it is the most delicately poised) is commonly the system that is most severely upset. Many of these lesions affect other bodily systems the central nervous system (perhaps because it is the most delicately poised) is commonly the system that is most severely upset. phenylketonuriacs phenylalanine hydroxylase is defective. Figure 21.2 shows that the failure to...

Role Of Mitochondria In Telodendria

Figure 1.8 Classification of neurons. A simple way of classifying neurons is by noting the number of processes springing from the perikaryon. The figure shows (A) unipolar neuron (e.g. mammalian somaesthetic sensory neuron) (B) bipolar neuron (e.g. retinal bipolar neuron) (C) multipolar neuron (e.g. mammalian motor neuron). There is a large nucleus, well-developed nucleolus (sometimes more than one), rich rough endoplasmic reticulum, prominent Golgi apparatus (again sometimes more than one) and...

Synaptic Significance Of Collisioncoupling Systems

It is not difficult to recognise the advantages of the G-protein system. It enables a single primary messenger to cause the release of a large number of second messengers into the cytosol. This allows a multifold amplification of the signal. The second messenger may, as we shall shortly see, initiate a variety of effects in the subsynaptic cell. Moreover, the type of second messenger released into the cytosol depends on the effector. The response of a subsynaptic cell to a given primary...

Organisation Of Synapses

The structure and function of synapses forms one of the most important areas of research in molecular neurobiology. We shall discuss the molecular detail in Chapters 15, 16 and 17. In this section we shall merely look in an introductory way at their organisation in the brain. Figure 1.16 shows the structure of a typical synapse in the CNS. The termination of the axon swells to form a 'bouton', as we noted in Section 1.3.1. The bouton contains a number of small (20-40 nm) vesicles which are...

The Ap Axis In Vertebrate Central Nervous Systems

In Chapter 1 we saw how the vertebrate central nervous system forms by the invagination of a primordial strip or plate of neurectoderm. This process is called neurulation and leads to the formation of a neural tube (see Figure 18.5). In vertebrates (but not in protochordates), along the line where the invaginating neurectoderm pinches off to form the tube, some cells are left behind. These cells constitute the neural crest. In other species, especially mammals, the neural crest cells (NCCs)...

Neuroses Psychoses And The Mindbrain Dichotomy

First of all let us subdivide the term 'mental illness' into two neurological ('organic') and psychological (or 'functional'). This subdivision is by no means clear cut. Taking the neurological category first, we find it is often useful to subdivide it further into conditions that have a clear anatomical substratum (e.g. multiple sclerosis, parkinsonism) and those where that substratum is more subtle (e.g. depression, schizophrenia). Turning to the second category (the psychological) we find...

The Submembranous Cytoskeleton

All eukaryotic cells possess some form of cyto-skeleton. We shall examine the neuron's cytoskele-ton again in Chapter 15. Here we will introduce the subject by a brief description of the best-known submembranous cytoskeleton - that found in ery-throcytes. Erythrocyte membranes can be obtained very easily. If blood is subjected to osmotic shock by being placed in hypotonic saline, the erythrocytes (RBCs) burst and appropriate centrifugation will separate the membrane fragments (ghosts) from the...

Cotranslational Insertion

It can be shown that the polypeptide chain manufactured at the ribosome is inserted directly into the lumen of the ER. But how does the ribosome find the ER Not all the proteins that a neuron manufactures are for export. Some of them will be for the usual 'housekeeping' activities of the perikaryon itself. It would be disastrous if these were to be delivered into the lumen of the ER and sent off for export The answer to this question seems to be that the first thirty or so amino acids in the...

Some Pathologies

Personal, social, economic dimensions - fuzzy distinction between neuroses and psychoses -mind brain dichotomy - differing therapies. Prions many different neurodegenerations -presently incurable - coded by gene on chr. 20 - aetiology - prions are replicative proteins -replicative mechanism - proliferative routes - transmissibility - can prions cross species barrier - therapies PKU many metabolic defects - PKU due to defect in phenylalanine-hydroxylase co-factors - lethal build-up of...

Mink Nervous System

It has turned out that subunits with only a single transmembrane domain have channel-forming properties. These so-called minimal K units, minK units, consist of a protein some 130 amino acids in length with a single a-helical transmembrane segment. MinK units were long a source of controversy. Evidently they could hardly form a K channel individually. Did they form a multimeric complex Eventually it was found that they were always associated with the KCNQ1 K channel where they acted as a...

Neurotransmitters And Neuromodulators

Complexity of synaptic structure of the brain. Infelicity of 'telephone exchange' image. Fuzzy distinction between neurotransmitters and neuromodulators. Ionotropic and metabotropic responses, punctate and diffusional transmission. Criteria for neurotransmitters. Neurotransmitters Acetylcholine synthesis - localisation - pharmacology - reuptake - feedback control - pre- and postsynaptic AChRs. Amino acids excitatory glutamate, aspartate -synthesis - wide distribution - NMDA - reuptake...

The Golgi Body and Posttranslational Modification

Golgibody Secretion

We noted in Chapter 3 that post-translational modification of polypeptides and proteins is very common. In particular we saw how some of the peptide neuromodulators - the opioids and enkephalins - are known to be derived from large precursor proteins or polyproteins by post-translational processing. In Chapter 4 we considered the evolutionary implications of this phenomenon. In this section we shall look at where this post-translational processing occurs. The first steps in post-translational...

Second Messenger Control Of Ion Channels

Neuropeptide Release Mechanism

So far in this chapter we have been considering very rapid events usually less than 5 ms in the postsynaptic membrane. We have seen how they may 'switch on' or 'switch off the postsynaptic neuron. The next thing we have to do is to remind ourselves that many transmitters do not directly open ion gates at all but work through collision-coupled second messenger systems. The outcome of these second messenger systems may be to affect the conductivity of ion gates elsewhere in the post-synaptic...

Organisation Of Neurons In The Brain

Neuron Transistors

To the naked eye a section of the mammalian brain seems to reveal two types of substance grey matter and white matter. White matter is composed of Figure 1.19 Synaptic contacts on the perikaryon of a spinal motor neuron. This reconstruction from serial electron micrographs shows how densely covered the perikaryon of a motor neuron is with large and small synaptic endings. From Poritsky 1969 , Journal of Comparative Neurology, 135, 423452 with permission. Figure 1.19 Synaptic contacts on the...

Huntingtons Disease Chorea Hd

Huntington's disease Huntington's chorea is one of a group of disorders of the basal ganglia which lead to jerky, rapid involuntary movements. The word 'chorea' is, indeed, derived from a Greek root meaning 'dance' and an earlier name for the condition was 'St Vitus' dance'. The striatum is particularly affected with many prominent neurons degenerating. The striatum, along with the other basal nuclei, is central to the neurophysiology of behavioural movements. It has been found that in many...

Vertebrate Nervous Systems

One of the best ways of getting a grip on the structure of the vertebrate nervous system is to follow its development. There has been an enormous increase in our understanding of this process in the last decade or so. This new understanding often goes under the provocative title 'evo-devo'. This draws attention to the fact that investigations of early developmental processes often throw light on early phases of animal evolution. An Figure 1.3 Embryology of the vertebrate brain idealised...