Hot Off the Press: Rich, can you comment?

[Guest guest]

Glia. 2005 May 12; [Epub ahead of print]

Excitotoxic oligodendrocyte death and axonal damage induced by

glutamate transporter inhibition.

Domercq M, Etxebarria E, -Samartin A, Matute C.

Departamento de Neurociencias, Universidad del Pais Vasco, Vizcaya,

Spain.

Glutamate uptake is crucial to terminate glutamate signaling and to

prevent excitotoxicity. The present study describes the expression

of functional glutamate transporters GLAST and GLT-1 in

oligodendrocytes by means of electrophysiology, uptake assays, and

immunocytochemistry.

Inhibition of glutamate uptake, both in oligodendrocyte cultures and

in isolated optic nerves, increases glutamate levels and causes

oligodendrocyte excitotoxicity, which is prevented by alpha-amino-3-

hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate

receptor antagonists.

Furthermore, glutamate transporter inhibitors or antisense

oligonucleotides applied onto the optic nerve in vivo lead to

oligodendroglial loss, massive demyelination, and severe axonal

damage. Overall, these results demonstrate that the integrity of

oligodendrocytes and white matter depends on proper glutamate

transporter function. Deregulated transporter activity may

contribute to acute and chronic white matter damage. © 2005 Wiley-

Liss, Inc.

PMID: 15892126 [PubMed - as supplied by publisher]

[Guest guest]

Hi, .

I'm not sure what sort of comments you are looking for on this. All

I have is the abstract, and I'm not sure how much you already know.

Nevertheless, I will run on a little, and maybe it will be of help.

First, the oligodendrocytes are the cells in the central nervous

system that have the responsibility for producing and maintaining

the myelin or white matter that serves as electrical insulation

around the axons, which are the part of the neurons that carry the

nerve impulses or action potentials.

Second, glutamate is the principal excitatory neurotransmitter in

the central nervous system. It is used to convey a nerve impulse

from one neuron to another across a gap called a synapse, and it is

also used to stimulate oligodendrocytes. These two cell types have

different types of receptors for glutamate, but they both utilize

glutamate as a neurotransmitter. Neurons can suffer from

excitotoxicity as well, but this paper is about the oligodendrocytes.

Excitotoxicity occurs when a cell receives too much stimulus in the

form of excitatory neurotransmitters. The mechanism involved in

excitotoxicity includes entry of calcium into the cell,

depolarization of mitochondria, increase in oxidizing free radicals,

and depletion of glutathione. Eventually, cell death can ensue.

The extracellular glutamate concentration is controlled by glutamate

transporters, which import glutamate into the cells.

These researchers report that if they inhibit the glutamate

transporters, the higher level of extracellular glutamate stimulates

the AMPA and kainin type receptors on the oligodendrocytes too much,

and they suffer from excitotoxicity. This kills the

oligodendrocytes, thus destroying myelin, and damage to the axons

themselves results as well.

They suggest that if there is a problem in the regulation of the

glutamate transporters, this is a mechanism that could produce white

matter damage.

Is this what you were looking for?

Rich

> Glia. 2005 May 12; [Epub ahead of print]

>

>

> Excitotoxic oligodendrocyte death and axonal damage induced by

> glutamate transporter inhibition.

>

> Domercq M, Etxebarria E, -Samartin A, Matute C.

>

> Departamento de Neurociencias, Universidad del Pais Vasco,

Vizcaya,

> Spain.

>

> Glutamate uptake is crucial to terminate glutamate signaling and

to

> prevent excitotoxicity. The present study describes the expression

> of functional glutamate transporters GLAST and GLT-1 in

> oligodendrocytes by means of electrophysiology, uptake assays, and

> immunocytochemistry.

>

> Inhibition of glutamate uptake, both in oligodendrocyte cultures

and

> in isolated optic nerves, increases glutamate levels and causes

> oligodendrocyte excitotoxicity, which is prevented by alpha-amino-

3-

> hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate

> receptor antagonists.

>

> Furthermore, glutamate transporter inhibitors or antisense

> oligonucleotides applied onto the optic nerve in vivo lead to

> oligodendroglial loss, massive demyelination, and severe axonal

> damage. Overall, these results demonstrate that the integrity of

> oligodendrocytes and white matter depends on proper glutamate

> transporter function. Deregulated transporter activity may

> contribute to acute and chronic white matter damage. © 2005

Wiley-

> Liss, Inc.

>

> PMID: 15892126 [PubMed - as supplied by publisher]

[Guest guest]

> Hi, .

>

> I'm not sure what sort of comments you are looking for on this.

All

> I have is the abstract, and I'm not sure how much you already

know.

>

> Nevertheless, I will run on a little, and maybe it will be of help.

>

> First, the oligodendrocytes are the cells in the central nervous

> system that have the responsibility for producing and maintaining

> the myelin or white matter that serves as electrical insulation

> around the axons, which are the part of the neurons that carry the

> nerve impulses or action potentials.

>

> Second, glutamate is the principal excitatory neurotransmitter in

> the central nervous system. It is used to convey a nerve impulse

> from one neuron to another across a gap called a synapse, and it

is

> also used to stimulate oligodendrocytes. These two cell types

have

> different types of receptors for glutamate, but they both utilize

> glutamate as a neurotransmitter. Neurons can suffer from

> excitotoxicity as well, but this paper is about the

oligodendrocytes.

>

> Excitotoxicity occurs when a cell receives too much stimulus in

the

> form of excitatory neurotransmitters. The mechanism involved in

> excitotoxicity includes entry of calcium into the cell,

> depolarization of mitochondria, increase in oxidizing free

radicals,

> and depletion of glutathione. Eventually, cell death can ensue.

>

> The extracellular glutamate concentration is controlled by

glutamate

> transporters, which import glutamate into the cells.

>

> These researchers report that if they inhibit the glutamate

> transporters, the higher level of extracellular glutamate

stimulates

> the AMPA and kainin type receptors on the oligodendrocytes too

much,

> and they suffer from excitotoxicity. This kills the

> oligodendrocytes, thus destroying myelin, and damage to the axons

> themselves results as well.

>

> They suggest that if there is a problem in the regulation of the

> glutamate transporters, this is a mechanism that could produce

white

> matter damage.

>

> Is this what you were looking for?

>

> Rich

Hi Rich

This is so interesting and I hope I am not going up the wrong

alleyway here but, my 88 year old father has just been diagnosed

with a white cell disease which stops the neurons from working

correctly and also stops the circulation getting to his legs as well

as his brain.

I am wondering whether taking a good whey product might help him in

the way it has helped me. Could building glutathione be helpful in

his case do you think because traditional medicine has nothing to

help him at all and it is so obvious he has lost so much of his

normal mental capacity amongst an inability to walk. BTW he will be

having an MRI scan very shortly to check the extensiveness of the

damage he has sustained so far which his doctor says is part of the

normal ageing process.

Thanks

Pam

[Guest guest]

Hi, Pam.

I'm sorry to hear about what your father is going through.

I don't know for sure whether taking a nondenatured whey protein

product would help him, but I think it is certainly possible.

I do know that two of the substances that commonly decrease in older

people are vitamin B12 (because they don't absorb it as well) and

glutathione. I'm not sure what the mechanism is for glutathione

depletion with advancing age, but I have read that the level of it

correlates well with how long a person will live.

Both B12 and glutathione are important for the brain. I don't know

what sort of white cell disease your father has, but glutathione is

also very important for the function of the white cells.

So I guess I would say that it is worth a try, if he is willing.

And I would suggest getting his B12 level checked (by methylmalonic

acid testing) also. If it's low, he could take it sublingually or

by injections.

Rich

> Hi Rich

>

> This is so interesting and I hope I am not going up the wrong

> alleyway here but, my 88 year old father has just been diagnosed

> with a white cell disease which stops the neurons from working

> correctly and also stops the circulation getting to his legs as

well

> as his brain.

>

> I am wondering whether taking a good whey product might help him

in

> the way it has helped me. Could building glutathione be helpful

in

> his case do you think because traditional medicine has nothing to

> help him at all and it is so obvious he has lost so much of his

> normal mental capacity amongst an inability to walk. BTW he will

be

> having an MRI scan very shortly to check the extensiveness of the

> damage he has sustained so far which his doctor says is part of

the

> normal ageing process.

>

> Thanks

>

> Pam

[Guest guest]

> Hi, Pam.

>

> I'm sorry to hear about what your father is going through.

>

> I don't know for sure whether taking a nondenatured whey protein

> product would help him, but I think it is certainly possible.

>

> I do know that two of the substances that commonly decrease in

older

> people are vitamin B12 (because they don't absorb it as well) and

> glutathione. I'm not sure what the mechanism is for glutathione

> depletion with advancing age, but I have read that the level of it

> correlates well with how long a person will live.

>

> Both B12 and glutathione are important for the brain. I don't

know

> what sort of white cell disease your father has, but glutathione

is

> also very important for the function of the white cells.

>

> So I guess I would say that it is worth a try, if he is willing.

> And I would suggest getting his B12 level checked (by

methylmalonic

> acid testing) also. If it's low, he could take it sublingually or

> by injections.

>

> Rich

>

Hi Rich

Thanks so much for the very good advice and I will certainly see if

I can get him started on the whey.

With regard to the B12 I hadn't thought of that but I have to have

monthly injections but also do well on daily methycobalmin by Thorne

which I just put under my tongue so I could easily get him some of

that too.

The NHS just goes by blood tests for levels of B12 but there is a

huge range and often the problem goes undetected as it did in my

case until I had live blood analysis which showed a great many very

large red blood cells but also the 24 hour urine test for B12

deficiency also showed a deficiency.

Best Wishes

Pam