Re: Glutamate transport in ALS

[Guest guest]

This is some histology of damaged ALS brains. The investigators knew

that expression of glutamate transporters was outta whack in ALS, so

to deepen that knowledge they used antibodies to stain particular

subtypes of glutamate transporters. They found that the subtype

expressed by neurons was deficient by 20%, but the kind expressed by

astroglia was down by 70% on average, sometimes 90%, in both motor

cortex and spinal cord. However, it says astroglia do not die in ALS.

Ann Tweedie of eurolyme once sent me this 'stract:

----------------------------------------------------

Acta Neurol Scand. 1988 Sep;78(3):181-4.

CNS-borreliosis selectively affecting central motor neurons.

Fredrikson S, Link H.

Department of Neurology, Karolinska Institutet, Huddinge Hospital,

Stockholm, Sweden.

A patient is described having Borrelia burgdorferi spirochetal

infection clinically affecting central motor neurons selectively and

without any sensory impairment. Diagnosis was based on elevated B.

burgdorferi IgG antibody titers in cerebrospinal fluid (CSF) and

titer normalization at clinical recovery. This occurred promptly and

was complete after penicillin treatment despite 14 months of

progressive central nervous system (CNS) dysfunction, favouring the

hypothesis of the presence of the organism within the CNS. CSF

findings characteristic of neuroborreliosis were registered,

including parallel occurrence of mononuclear pleocytosis, severe

blood-brain barrier damage and marked CSF IgM index elevation of

prolonged duration. Some earlier reports of CNS manifestations

related to B. burgdorferi are reviewed.

Publication Types:

Case Reports

PMID: 3227803 [PubMed - indexed for MEDLINE]

------------------------------------------------

> See, I'm posting an abstract. Woohoo. Too bad I can't read it. But

> for reasons I'd rather not go into, I have to look at ALS now.

>

> Can anyone tell me what this says?

>

>

>

> Ann Neurol. 1995 Jul;38(1):73-84. Related Articles, Links

>

>

> Selective loss of glial glutamate transporter GLT-1 in amyotrophic

> lateral sclerosis.

>

> Rothstein JD, Van Kammen M, Levey AI, LJ, Kuncl RW.

>

> Department of Neurology, s Hopkins University, Baltimore, MD,

> USA.

>

> The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is

> unknown, but defects in synaptosomal high-affinity glutamate

> transport have been observed. In experimental models, chronic loss

> of glutamate transport can produce a loss of motor neurons and,

> therefore, could contribute to the disease. With the recent cloning

> of three glutamate transporters, i.e., EAAC1, GLT-1, and GLAST, it

> has become possible to determine if the loss of glutamate transport

> in ALS is subtype specific. We developed C-terminal,

> antioligopeptide antibodies that were specific for each glutamate

> transporter. EAAC1 is selective for neurons, while GLT-1 and GLAST

> are selective for astroglia. Tissue from various brain regions of

> ALS patients and controls were examined by immunoblot or

> immunocytochemical methods for each transporter subtype. All tissue

> was matched for age and postmortem delay. GLT-1 immunoreactive

> protein was severely decreased in ALS, both in motor cortex (71%

> decrease compared with control) and in spinal cord. In

approximately

> a quarter of the ALS motor cortex specimens, the loss of GLT-1

> protein (90% decrease from control) was dramatic. By contrast,

there

> was only a modest loss (20% decrease from control) of

immunoreactive

> protein EAAC1 in ALS motor cortex, and there was no appreciable

> change in GLAST. The minor loss of EAAC1 could be secondary to loss

> of cortical motor neurons. As a comparison, glial fibrillary acidic

> protein, which is selectively localized to astroglia, was not

> changed in ALS motor cortex. Because there is no loss of astroglia

> in ALS, the dramatic abnormalities in GLT-1 could reflect a primary

> defect in GLT-1 protein, a secondary loss due to down regulation,

or

> other toxic processes.

>

> PMID: 7611729 [PubMed - indexed for MEDLINE]

[Guest guest]

I wish I could read it too.

This article at www.neurorelief.com (they do urine tests for

neurotransmitter levels, including glutamate) talks about ALS as a

problem of glutamate-mediated excitoxicity:

http://www.neurorelief.com/newsletterarchive.php?issue=352

Maybe you could try one of the glutamate antagonists they mention,

and see if it helps your symptoms.

> See, I'm posting an abstract. Woohoo. Too bad I can't read it. But

> for reasons I'd rather not go into, I have to look at ALS now.

>

> Can anyone tell me what this says?

>

>

>

> Ann Neurol. 1995 Jul;38(1):73-84. Related Articles, Links

>

>

> Selective loss of glial glutamate transporter GLT-1 in amyotrophic

> lateral sclerosis.

>

> Rothstein JD, Van Kammen M, Levey AI, LJ, Kuncl RW.

>

> Department of Neurology, s Hopkins University, Baltimore, MD,

> USA.

>

> The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS) is

> unknown, but defects in synaptosomal high-affinity glutamate

> transport have been observed. In experimental models, chronic loss

> of glutamate transport can produce a loss of motor neurons and,

> therefore, could contribute to the disease. With the recent cloning

> of three glutamate transporters, i.e., EAAC1, GLT-1, and GLAST, it

> has become possible to determine if the loss of glutamate transport

> in ALS is subtype specific. We developed C-terminal,

> antioligopeptide antibodies that were specific for each glutamate

> transporter. EAAC1 is selective for neurons, while GLT-1 and GLAST

> are selective for astroglia. Tissue from various brain regions of

> ALS patients and controls were examined by immunoblot or

> immunocytochemical methods for each transporter subtype. All tissue

> was matched for age and postmortem delay. GLT-1 immunoreactive

> protein was severely decreased in ALS, both in motor cortex (71%

> decrease compared with control) and in spinal cord. In

approximately

> a quarter of the ALS motor cortex specimens, the loss of GLT-1

> protein (90% decrease from control) was dramatic. By contrast,

there

> was only a modest loss (20% decrease from control) of

immunoreactive

> protein EAAC1 in ALS motor cortex, and there was no appreciable

> change in GLAST. The minor loss of EAAC1 could be secondary to loss

> of cortical motor neurons. As a comparison, glial fibrillary acidic

> protein, which is selectively localized to astroglia, was not

> changed in ALS motor cortex. Because there is no loss of astroglia

> in ALS, the dramatic abnormalities in GLT-1 could reflect a primary

> defect in GLT-1 protein, a secondary loss due to down regulation,

or

> other toxic processes.

>

> PMID: 7611729 [PubMed - indexed for MEDLINE]

[Guest guest]

Hey, thanks a ton for that reference. Theanine and taurine keep

coming up. I will pursue this.

> > See, I'm posting an abstract. Woohoo. Too bad I can't read it.

But

> > for reasons I'd rather not go into, I have to look at ALS now.

> >

> > Can anyone tell me what this says?

> >

> >

> >

> > Ann Neurol. 1995 Jul;38(1):73-84. Related Articles, Links

> >

> >

> > Selective loss of glial glutamate transporter GLT-1 in

amyotrophic

> > lateral sclerosis.

> >

> > Rothstein JD, Van Kammen M, Levey AI, LJ, Kuncl RW.

> >

> > Department of Neurology, s Hopkins University, Baltimore,

MD,

> > USA.

> >

> > The pathogenesis of sporadic amyotrophic lateral sclerosis (ALS)

is

> > unknown, but defects in synaptosomal high-affinity glutamate

> > transport have been observed. In experimental models, chronic

loss

> > of glutamate transport can produce a loss of motor neurons and,

> > therefore, could contribute to the disease. With the recent

cloning

> > of three glutamate transporters, i.e., EAAC1, GLT-1, and GLAST,

it

> > has become possible to determine if the loss of glutamate

transport

> > in ALS is subtype specific. We developed C-terminal,

> > antioligopeptide antibodies that were specific for each

glutamate

> > transporter. EAAC1 is selective for neurons, while GLT-1 and

GLAST

> > are selective for astroglia. Tissue from various brain regions

of

> > ALS patients and controls were examined by immunoblot or

> > immunocytochemical methods for each transporter subtype. All

tissue

> > was matched for age and postmortem delay. GLT-1 immunoreactive

> > protein was severely decreased in ALS, both in motor cortex (71%

> > decrease compared with control) and in spinal cord. In

> approximately

> > a quarter of the ALS motor cortex specimens, the loss of GLT-1

> > protein (90% decrease from control) was dramatic. By contrast,

> there

> > was only a modest loss (20% decrease from control) of

> immunoreactive

> > protein EAAC1 in ALS motor cortex, and there was no appreciable

> > change in GLAST. The minor loss of EAAC1 could be secondary to

loss

> > of cortical motor neurons. As a comparison, glial fibrillary

acidic

> > protein, which is selectively localized to astroglia, was not

> > changed in ALS motor cortex. Because there is no loss of

astroglia

> > in ALS, the dramatic abnormalities in GLT-1 could reflect a

primary

> > defect in GLT-1 protein, a secondary loss due to down

regulation,

> or

> > other toxic processes.

> >

> > PMID: 7611729 [PubMed - indexed for MEDLINE]