3 Lifespan changes in the nervous system

Chapter contents

Introduction

Neurodevelopment

Neurulation

Embryology of the spinal cord

Development and role of the meninges

Developmental malformations

Cell differentiation

Synapse formation

Ageing and the nervous system

Redundant message theory

Pre-programmed ageing theory

Mutational DNA theory

Physiological consequences of neuronal ageing

Learning outcomes

At the end of this chapter you should be able to:

• identify the key changes and time points in the process of neurulation

• explain what is meant by the term ‘cell differentiation’ and what is thought to influence this process in the early stages of neurodevelopment

• describe the cause of the condition known as spina bifida and outline the defects found in the three types of spina bifida: occulta, meningocoele and myelomenigocoele

• discuss the basic ideas behind some of the general theories of ageing

• highlight the main physiological, biochemical and pathological changes associated with ageing.

Introduction

Allied health professionals (AHPs) who work in rehabilitation encounter people across the lifespan; from babies with cerebral palsy, children with brain damage following meningitis, young adults with spinal cord lesions, to older people with Alzheimer’s disease. AHPs need to have a sound understanding of the normal development and ageing of the nervous system in order to understand the impact of developmental disorders, injury, illness and degenerative conditions.

A significant amount of neuroscience is targeted at trying to gain further understanding as to how the system operates and what contribution is made by all of the component parts. There is much interest in both ends of the spectrum, i.e. the in utero development and the age-related deterioration of the system. It is hoped that by gaining a more detailed understanding of how the system developed at the beginning, we may gain further insight into what happens as the system starts to break down during the process of normal ageing, and vice versa. As a result of this interest this chapter will focus on the two extremes of lifespan changes – neurodevelopment and ageing of the nervous system.

Neurodevelopment

Approximately 12 hours after the moment of fertilisation of the female reproductive tract the zygote divides in two, followed by further divisions every 12 hours or so into four cells, then eight, etc. This process of division continues with little increase in size, until about day 7 when implantation of the embryo occurs. By embryonic day 15 (E15) the structures necessary to sustain the embryo are in place, i.e. the placenta, amniotic cavity and yolk sac (see Fig. 3.1).

Fig. 3.1 • Embryonic day 15 (E15).

With permission from the Open University

At this stage the embryo is a flat germ disc comprising two layers of cells known as the endoderm (from the Greek words endo and derma, meaning inner skin) and the ectoderm (from the Greek for outer skin). At about E15 these two layers begin to separate and form a cavity between them into which ectodermal cells flow to create the mesoderm (middle skin).

Neurulation

Around day 22 the process of neurulation begins roughly halfway along the neural plate and in the early stages of the process the cranial and caudal ends stay open. The process then spreads along the groove with the cranial neuropore closing around day 25 and the closure of the caudal neuropore taking place around day 27. The closure in both directions occurs in a segmented way and this segmental arrangement is retained in the spinal cord (see Figs 3.2, 3.3 and 3.4).

Fig. 3.2 • Embryonic day 21 (E21).

With permission from the Open University

Fig. 3.3 • Closure of the neural tube.

With permission from the Open University

Fig. 3.4 • Embryology of the spinal cord.

With permission from the Open University

The cells just above the neural tube form the neural crest and these cells will migrate from the neural tube to form the neurones and glia of the sensory and sympathetic ganglia, the neurosecretory cells of the adrenal gland and the enteric nervous system (a subdivision of the peripheral nervous system controlling the gastrointestinal system).

Embryology of the spinal cord

The spinal cord develops from the part of neural tube caudal to the 4th pair of somites (paired blocks of mesoderm) segmentally arranged on either side of the neural groove. After neurulation, the lateral walls of the tube thicken and are covered by neuroepithelium, which will ultimately form the neurones and glia of the spinal cord. The cells form two plates on each side:

• the anterior basal plate

• the posterior alar plate

and these plates are separated by a shallow groove known as the sulcans limitans.

By week 10 the lumen of the neural tube starts to form a small central canal. It is at this point that the alar plate cells develop into the ascending projection neurones and interneurones that will subsequently form sensory pathways and reflex circuits. Simultaneously, the basal plate cells differentiate into the motor neurones and interneurones that will transmit information out of the spinal cord down to the muscles (i.e. the descending projection neurones). The cells in the thoracic segment develop into the sympathetic preganglionic neurones, while the cells in the sacral segment develop into the parasympathetic preganglionic neurones – thereby forming both parts of the autonomic nervous system (see Chapter 1).

Development and role of the meninges

The brain and spinal cord are surrounded by three connective tissue layers, the meninges. These three layers are:

• the dura mater

• the arachnoid mater

• the pia mater.

The dura mater (dura meaning tough) is a tough, inelastic membrane which is actually composed of two layers, one round the spinal cord and brain and the outer fused with the periosteum (or lining) of the cranium. The inner layer of the dura is fused to the outer one except over the dural and venous sinuses. This structure allows the venous blood to drain into these sinuses on the return journey to the heart. The dura is separated from the periosteum of the vertebral canal by the epidural space (i.e. the space into which an epidural anaesthetic would be injected). If the blood vessels in the dura were to rupture and bleed into the space between the dura and the arachnoid mater layers, this would result in a subdural haemorrhage or haematoma. The arachnoid mater (arachnoid meaning spiderlike) is a very delicate, highly vascularised layer. In fact it is the density of the vasculature that gives the arachnoid its ‘cobwebby’ appearance. The space between the arachnoid and underlying pia is the subarachnoid space and it is through this space that the cerebrospinal fluid (CSF) flows. This would also be the location of the type of stroke known as a subarachnoid haemorrhage. The pia mater (pia meaning gentle

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