The Brain and Glial Cells

[Guest guest]

The following news item really captured my attention the other day, since it

discussed structures in the brain which had first intrigued me during the

early days of my Master's degree in applied mathematics on a topic in brain

research. It concerns cells called glia which are much more numerous than

neurons in the central nervous system and which often tend to be glossed over

in discussions of brain function. I always felt that these cells do not

simply act as supportive or nutritive structures for the less numerous

neurons, but somehow must play a vital role in brain processing.

This recent news release appears directly below and is followed by an extract

from my MSc on the same topic. I was delighted to see that my early interest

in glial cells was not misplaced.

Mel Siff

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Glial Cells and How the Brain Works - News Article: January 2001

Stanford University scientists have filled an important gap in

understanding how the brain works, discovering what prompts nerve cells to

build the vital connections they need to communicate.

Glial cells, long thought to be just passive scaffolding for the brain's

all-important neurons, are directly responsible for how many connections

neurons form so they can talk to each other, the scientists report in

Friday's edition of the journal Science (Jan 25, 2001).

The surprise discovery could lead to better understanding of how memory

forms, and perhaps shed new light on what causes certain brain diseases such

as epilepsy or amytrophic lateral sclerosis. " I'll bet money that there is

going to be some disease that is a breakdown in this regulation, " said Dr

s, a neurobiologist who wasn't involved in the new research

and calls it a major finding.

More immediately important is the basic understanding of how glial cells

affect those vital neuron connections called synapses, he said. " If you

want to understand how the brain computes, you have to understand how they

form, " explained s, who is with the Salk Institute for Biological

Studies in La Jolla, California.

Glial cells make up most of the brain's cells - for every one neuron there

are 10 glia, says Stanford lead researcher Dr Ben Barres. The scientific

dogma was that they only supported neurons, perhaps by providing nutrition,

but nobody really knew. So Barres and postdoctoral student Ullian set

out to uncover the function of a main glial cell called an astrocyte.

Neurons are nerve cells that send and receive messages by swapping chemical

signals, such as signals that say you're suffering pain or move that leg to

walk or retrieve that memory. To do that communicating, neurons first must

form synapses.

Scientists once thought neurons were wired to simply build as many synapses

as needed. Not so, Barres' team discovered - young neurons form only a few

immature synapses when there are no astrocytes nearby, he said.

But add astrocytes to neurons in laboratory dishes and suddenly they form

seven times more synapses, and strong, healthy ones, Barres said. Ullian

confirmed the finding with another experiment in which he took astrocytes

away and the synapses promptly started shrivelling.

" People really have not had a good feel for how the brain controls the

number of synapses - is the neuron just born with it or are there

environmental signals? " Barres said. " Our results show absolutely clearly

that environmental signals can have a profound effect on how many synapses

neurons can have. " What does it mean for brain research? " We're very

interested in the possible disease implications, " he said.

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Neuroglia

(M C Siff 'Modelling of Electroencephalographic Phenomena', MSc

Dissertation, University of the Witwatersrand, South Africa, 1977)

The neurons constitute only a small fraction of the total brain volume. There

are virtually no interstitial spaces in the brain and much of the remaining

volume is filled with a host of different glial cells which surround the

neurons and the blood capillaries. The neuroglial cells, which outnumber the

neurons by a factor of more than ten, are generally classified into several

groups: astrocytes, oligodendrocytes and ependymal cells. Living cells from

these groups have been observed to change their outer shape in vitro, so it

is possible that glial cells in the brain possess a marked plasticity which

depends on particular environmental factors (Hild, 1963).

Galambos (1961) has remarked that 'An untutored observer constructing for

himself a model of the brain from electron microscope pictures alone might

well describe it as a huge collection of glial cells through which a nerve

process occasionally wanders; those of us well instructed in the conventions,

however, see a marvellously intricate arrangement of nerve cells held

together by relatively unimportant non-neural elements'.

Indeed, the conventional view is that the glial cell cytoplasm fills a

supportive role for the neurons and provides certain metabolites for the

neural networks.

However, by virtue of their immense numbers and their intimate contact with

the neurons, one should expect some form of chemical and electrical coupling

between glia and neurons. It should be remembered that discharge of the

neurons is accompanied by the passage of ions between the interior of the

cell and its environment, which consists largely of neuroglia. This fact

alone indicates that the role of the glia cannot be strictly passive. Hertz

has suggested that normal neuron transmission might be accompanied by

chemical transmission of ions from the neuron to neighbouring neuroglia and

then to other neurons, as outlined in Figure 4.9 (Gerardin, 1968).

[Figure 4.9 here]

One distinct difference between glia and neurons lies in the ability of glial

tissue to multiply by mitosis and to repair itself. The neuron does not

undergo mitosis and regrowth occurs so slowly that only a few modern

experiments have even managed to establish that repair of neurons does occur.

Rose and his colleagues have shown that axons and dendrites eventually regrow

in narrow lesions produced in the brain by deuteron irradiation (Rose et al,

1969). Pribram (1969) has suggested that neural growth is somehow guided by

the glial matrix is which damaged neurons are embedded. The ability of the

brain to continue functioning after suffering extensive tissue damage has

been attributed by some workers to such neuroglial mechanisms (Galambos,1961).

There appears to be some differentiation between the growth patterns followed

by neurons and glia in the human brain. The number of nerve cells reaches a

maximum early in the development of the brain, while glial cells multiply at

a later stage. Dobbing (1967) and Sands showed that the human brain grows in

two separate spurts: the first, from the 15th to the 20th week of pregnancy,

which possibly marks the proliferation of neurons ; and the second, beginning

the 25th week and lasting probably until the second year of life, a phase

which may be devoted to the growth of glia.

An interesting observation concerns the increase in the ratio of glia to

neurons with an increase in complexity of the central nervous system in the

species. This ratio reaches the highest value in man and Is one of the few

quantitative measures which is characteristic of the human (Dobbing, 1967).

In occupying a strategic position between the neurons and the blood

capillaries, the glia play a definite role in the passage of metabolites

between the neurons and themselves. Hyden (1962, 1963, 1969) has done

considerable research into the biochemistry of a possible neuron-glial

symbiosis. He has monitored energy processes and measured levels of RNA,

proteins and enzymes in neurons and neuroglia under various states of

excitation and concludes that these two types of cell are energetically

linked together in a coupled system. In fact, stimulation greatly increases

energy consumption in the neuron, but does not alter the state of the glia,

which suggests that the neuron has priority access to energy supplies when

its functional demands increase.

All types of glial cell exhibit a resting potential of 50 to 70 millivolts

and under electrical stimulation produce a decrease in potential whose

duration is about 1000 times longer than the responses in neurons (Hild 1963,

Tasaki and Chang, 1958). The glial cell membrane has a resistance of 3-10

ohms/cm2, a value which is about 100 to 500 times less than the

corresponding figure for the neuronal membrane.

The slow potentials associated with glial response have led some researchers

to suggest that the steady potential phenomena of the brain are due to glial,

rather than neural, activity (Rowland 1968). Some experimental support for

this theory has arisen from the work of Svaetichin who used photic (light)

stimulation to elicit electrical response from the retinal glial cell of

certain fish (Galambos 1961). He showed a definite correlation between

transretinal steady potential shifts and the glial membrane potential

responses to light. In addition, the Russian scientist, Aladjalova, has

stated that 'the slow processes reflect neurohormonal relations in which the

dendrites play a major role. The slow electrical phenomena reflect the

results of higher cortical functions being combined with metabolic activity

aided by the mechanisms of cortico-hypothalamic integration'. There is little

doubt that the glial tissue plays some metabolic role in the brain, so this

statement suggests the existence of a possible link between the glia and the

DC activity of the brain.

There is a phenomenon called 'cortical spreading depression (CSD) which

prevents the execution of learned responses in an animal and abolishes the

EEG and the steady potential usually present between the cortical surface and

the ventricle (Leao, 1951). Galambos suggests that, since an exclusively

neuron theory has never explained these facts, a glial mechanism could

complement the present theories. Furthermore, experiments on cats have shown

that inhibitors of a glial enzyme, pseudocholinesterase, have a marked

influence on the EEG, evoked responses and behaviour (Galambos, 1961).

The preceding data imply the existence of a phase-locking mechanism which

operates under excitation to synchronize neuron and glial activity. The slow

glial potentials conceivably program and organize transient neural activity

in an integration over time which ensures efficient operation of the organism

under all states of excitation.

Another observation which may have a bearing on the issue is the slowing of

the dominant human alpha rhythm with advancing age. The decrease in the alpha

frequency from about 10 Hz to 8 Hz is probably due to a reduction of blood

flow and metabolites in the brain (Arrigo, 1976). Administration of the ergot

derivative, 'hydergine' (dihydro-ergotoxidemethansulphonate), tends to

increase the senile dominant alpha rhythm. Since glial cells participate in

the transport of cerebral metabolites, including such drugs, they might also

play some controlling role in the mechanisms responsible for the alpha rhythm.

It is true that there is insufficient information about glial activity to

allow the above speculations to seriously challenge the present status of the

neuron theory, but this certainly does not justify permanent relegation of

the glia to a minor role before extensive research has resolved the situation.

Galambos (1961) has offered the scheme of Figure 4.10 to incorporate the

glial cells in a composite bioelectric unit. All the contacts depicted in

this model appear abundantly in electron micrographs of central nervous

tissue, so the anatomical basis for such a unit is sound.

However, it remains to be ascertained whether 'gliapses', like synapses, are

one-way filters and whether entities such as 'excitatory postgliaptic

potentials' (EPGPs) and 'inhibitory postgliaptic potentials' (IPGPs) exist. A

general model involving several such units would undoubtedly be more complex

to develop than existing neuron models of brain function, but in the long run

such a model could provide a better understanding of the brain.

[Figure 4.10 here]

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[Guest guest]

Mcsiff@a... wrote:

<The following news item really captured my attention the other day,

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Glial Cells and How the Brain Works - News Article: January 2001 >

Wow ... thank you Dr. Siff.

It is fascinating.

Noemi Lee, PT

London, UK