New research on glutamate receptor damage

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New research on glutamate receptor damage

Postby dignan » Tue Jan 24, 2006 3:28 pm

I don't think this study has been posted here yet, but sometimes it's hard to keep up.



Breakthrough in brain injury study at University of Leicester

Drs Robert Fern and Mike Salter of the Department of Cell Physiology and Pharmocology at the University of Leicester had their findings published in the science journal Nature.

Their study is particularly important as it identifies the cause of damage to the brain and the mechanism by which this occcurs - thereby raising the possibility of drugs being developed in the future which may help to reduce injury and the disease states that follow.

Dr Fern said: "This project has taken over a year to complete and has produced some rather important findings. We believe that we may have opened a new window into how the brain becomes damaged in a number of important diseases ranging from stroke to multiple sclerosis and spinal cord injury. We will now continue to study the particular brain receptor that is involved in the hope of discovering a way to block the receptor and therefore avert brain injury for a large number of patients."

This work was supported by a grant from the National Institutes of Neurological Disorders and Stroke to R.F.


PLEASE FIND FOLLOWING AN EXPALANATORY NOTE ABOUT THE RESEARCH AT LEICESTER

The brain is the organ responsible for our thoughts, memories, sensations and emotions. All these functions occur because neurons, the "little grey cells" of Agatha Christie's Hercule Poirot, are able to pass signals between one another using a chemical called glutamate.

Glutamate is released by neuronal structures called synapses and interacts with special receptors on neighboring neurons. While most people will have heard of neurons, it is not commonly known that only about half of the brain is actually made up of these cells, with the remainder being made up of non-neuronal cells called glial cells.

Neurons rely on glial cells for protection and sustenance and form a particularly close partnership with a kind of a glial cell called an oligodendrocyte. Oligodendrocytes have processes that wrap tightly around neurons, insulating them and allowing signals to speed quickly from neuron to neuron. They produce a white substance called myelin which acts like an electrical insulator and these cells can be thought of as the "little white cells" of the brain, with areas of the brain rich in oligodendrocytes having a characteristic white appearance.

Damage to oligodendrocytes is catastrophic to the brain, producing debilitating diseases such as cerebral palsy and multiple sclerosis.

We have been working to identify potential causes of this injury and have found that glutamate release acting upon glutamate receptors is causing damage to the oligodendrocyte cell processes. As a result of this damage the oligodendrocytes are not able to insulate the neurons and this manifests itself in sufferers as an inability to control basic functions such as speech and movement. The work we have completed shows that glutamate receptors are located on oligodendrocyte processes and that over activation of the receptor leads to injury. It is ironic that the receptor that is responsible for transmitting signals between neurons in healthy brain is also the cause of suffering in many cases of neurological disease. The identification of a specific receptor as being responsible is particularly important as it raises the possibility of drugs being developed in the future which may help to reduce injury and the disease states that follow.

http://www.eurekalert.org/pub_releases/ ... 012406.php
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Postby OddDuck » Wed Jan 25, 2006 5:21 am

Yep, we here have had many discussions regarding the role of glutamate in MS. The most recent one (which you might find interesting to review) was just a little while ago under the thread called "Apoptosis".

They have found that excess glutamate and its receptors plays a large role in Huntington's Disease (HD). I pasted the abstract with regard to that in that thread, also.

Sharon, Robin and I have speculated quite a few times about the role of glutamate, and yes............there are several drugs (oral, too) on the market now that will drastically help to reduce glutamate. They just aren't used (yet) in MS.

Once again, the "patients" are ahead of the "researchers"! :wink:

It's nice to see, though, that maybe some of them are catching up to us.

Best!

Deb

EDIT: Oh............and what plays a LARGE part in regulating the glutamate, among other things? My, my.............it's the HPA axis. They just keep going round and round, but they never stop for a second to take stock of where they have arrived at! :roll:
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Postby OddDuck » Wed Jan 25, 2006 5:48 am

Oh, and for those who WOULD like to read up a little more on the connections with regard to glutamate and how glutamate works, etc., I did find something that is written in much better "layman's" terms that I think is interesting for all to take a look at. It is a little easier reading than some of the more technical stuff some of us get into.

It's at: http://www.cnsspectrums.com/article.php3?id=25

Although not a popular notion, I have said to my "friends" at Vandy more than once, that if you look at MS VERY closely and do some physiological comparisons, you could say (and not really be incorrect) that MS can be classified as an "affective disorder".

As you will read quite often, it is stated that it is "puzzling" that MS sufferers often also suffer from clinical depression and the two are tightly interwoven. Uh.........I say........no, it is not all that puzzling! :?

So, then, let's turn it around. Can or should clinical depression or any of the other affective disorders also be labeled as an autoimmune disease, too? Or should researchers begin to think a little more "out of the box" with regard to MS? Especially given the more recent research that we see, as posted recently here, that is so duplicative of the same research findings that is coming out with regard to the pathophysiology of affective disorders?

And most of the pharmacological agents that work well with regard to regulation of all of this dysfunction being discussed herein, and is highly probable (and proven) to be at the very least neuroprotective, is ............ TCA anti-depressants.

hmmmmmmmmmmm...................


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Postby viper498 » Wed Jan 25, 2006 7:19 am

What is the HPA Axis, what is the connection to glutamate in laymans terms.


I can understand the principal that they make findings and never put the connections together, this is very typical...
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Postby dignan » Wed Jan 25, 2006 9:05 am

For me, the unique discovery from this research is that there are glutamate receptors located on oligodendrocyte processes that are injured through over activation. The researchers sound like they will now focus on finding drugs/substances that act on these receptors, not necessarily on glutamate itself. Any novel avenue of research like this is most welcome in my eyes.
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Postby bromley » Wed Jan 25, 2006 9:10 am

Deb,

You are right that glutamate keeps cropping up.

The article also refers to glutamate being involved in cerebral palsy. Coincidently, there was a research paper a few weeks ago that linked cerebral palsy with viruses (mothers who were infected with a virus during pregnancy were much more likely to have child with cerebral palsy).

The so called 'outbreaks' of MS suggest that MS might be triggered by an infectious agent, perhaps EBV. But how might these lead to too much Glutamate? Any views?

And how does excess glutamate lead to the immune system involvement? Does the glutamate start doing damage and then the immune system gets involved to mop up the mess? And is it the glutatmate that is responsible for the damage to myelin and nerve fibres? I assume that if the glutamate kills off the myelin producing cells then the nerve fibres begin to degenerate because they are not getting the required support.

But why would improvements in EDSS be seen in drugs such as Campath, Rituximab and Daclizumab?

Sorry for all the questions Deb. I just can't get my head round the sequence of all these events.

In layman's terms something happens which creates excess glutamate, this kills of myelin making cells, nerve fibres which are wrapped in myelin start to lose their protective coating, the immune system gets involved and.... This is a very complex story and I now have some sympathy with the researchers. I suppose the test is whether, if you reduce the glutamate level, then myelin making cells can do their job, nerve fibres get the support they need, the immune system doesn't get involved so no more attacks.

The death of myelin making cells before the immune attack was indentified by Prineas and Barnett so would fit with the glutamate theory. Of course the researchers have primarily focused on the immune system attack as the initiator of the problem. The failure of the immune system drugs to stop the underlying progression of the disease would also support the glutamate theory.


I hope, somewhere, that someone is modelling all the possible options for how this disease kicks off, progresses etc. I also hope that there are some small trials of the drugs that you say can reduce excessive glutamate (perhaps you could send me some in the post).

But this research paper looks like a step in the right direction (and is written in a way I actually understand).

Ian

I love the irony of this disease in relation to depression. It sounds as if a vulnerability to depression kicks off the disease, which in turn can make you depressed (because you have a horrible disease), but the solution is to take anti-depressants. It come rounds full circle. I hope this all pans out. A couple of anti-depressants tablets each day would certainly be better than the injectibles or a dose of chemo.
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Postby OddDuck » Wed Jan 25, 2006 11:54 am

The thing is, Ian, that it is believed that several of these "dysfunctions" (for lack of a better term) are all going on simultaneously, or in such rapid chain reactions that it is almost impossible to isolate any "one" process that can be identified as the "beginning" of MS.

Hence why I also try to stay away from causal relationships. I'm still not certain that will really get anyone anywhere. It's like epilepsy.........what's the "cause" of that? Who cares now? You know why? Because we have effective treatments for it. That's the only reason (in my humble opinion). Do you see a huge push or drives to find the cause of epilepsy? Nope.

So, as I think Robin has mentioned himself a few times, if one or more of these chain reactions can be stopped or reversed or prevented, then we're all the more ahead of the game that way. You can't pin this down to any ONE sequence of events. It won't work.

What I would say is that as many areas as possible should be treated at the same time........something for prevention, something for neuroprotection, AND something for regeneration.

Confusing? Yep! I'm just not certain that an easy way to unravel it even exists.

:(

Deb
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Postby dignan » Wed Jan 25, 2006 12:33 pm

Bromley, your question about glutamate and drug trials was intriguing, so I couldn't resist doing a quick check. I came up with 2 possibilities...



Glutamate inhibition in MS: the neuroprotective properties of riluzole.

J Neurol Sci. 2005 Jun 15;233(1-2):113-5. Epub 2005 Apr 20.
Killestein J, Kalkers NF, Polman CH.
Department of Neurology, VU Medical Centre, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands. J.Killestein@vumc.nl

In addition to demyelination and damage to oligodendrocytes, axonal injury and neuronal cell death are dominating histopathological characteristics of multiple sclerosis (MS). Still little is known about the cause of the damage. Extracellular accumulation of glutamate contributes to excitotoxic injury of neurons and glial cells, suggesting that the maintenance of subtoxic extracellular glutamate levels may be crucial. Riluzole is a neuroprotective agent that inhibits the release of glutamate from nerve terminals and modulates glutamate, i.e., kainate and NMDA receptors. It inhibits excitotoxic injury in several experimental models of neurodegenerative disease. We performed a small run-in versus treatment MR-monitored pilot study in 16 primary progressive MS patients. The results suggest that riluzole reduces the rate of cervical cord atrophy and the development of T1 hypointense lesions on magnetic resonance imaging in primary progressive MS. The rate of brain atrophy was only slightly decreased. The results indicate an effect on mechanisms involving lesion evolution and axonal loss, but no clear effect on new lesion formation. However, the data suffer from several limitations and must be confirmed in future trials.

<shortened url>



Low dose naltrexone therapy in multiple sclerosis.

Med Hypotheses. 2005;64(4):721-4.
Agrawal YP.
Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Room 153 B MRC, 200 Hawkins Drive, Iowa City, IA 52242-1182, USA. yashpal-agrawal@uiowa.edu

The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial.

<shortened url>
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Postby HappyDaddy » Thu Jan 26, 2006 2:05 am

Just an idea from the CpN website but I'll let somebody else (more knowledgeable) explain it.

CpN uses up melatonin and melatonin seems to be important in controlling glutamate ...
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Postby OddDuck » Thu Jan 26, 2006 5:24 am

Earlier (above), Viper asked what the HPA axis was. That has been asked before, and I believe a good outline in layman's terms was presented in our previous thread: http://www.thisisms.com/modules.php?nam ... hlight=hpa

Go take a look there. I think folks will find it interesting. (I apologize that these threads I am directing you to are mainly the ones where I have posted the explanations, etc. I guess I am just a tenacious researcher! :P )

How the HPA relates to glutamate (and glucocorticoids) is nicely explained in the article I pasted a link to above (in this thread), i.e. http://www.cnsspectrums.com/article.php3?id=25

Some of this stuff just isn't easy to explain! That's probably why neuros have trouble answering these kinds of questions from patients, now that I think of it! One answer only connects to another, and so on.........

Deb
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Postby OddDuck » Thu Jan 26, 2006 5:51 am

Ok...........melatonin........another interesting avenue (which all still connects with everything else).

I found a fairly good description of melatonin from http://www.aphroditewomenshealth.com/ne ... news.shtml:

Cortisol, melatonin, and leptin are regulatory hormones with typical circadian rhythms that regulate various physiological and metabolic functions. Another main regulator is the hypothalamic-pituitaryadrenal (HPA) axis, which coordinates several biological functions. The circadian rhythms represent the biological endocrine clock, whereas the HPA represents the stress-induced biological response. However, the interplay between these two main regulators of biological functions is not well understood. Therefore, observations of irregular secretions of circadian neuroendocrine secretions inclusive of cortisol are of special interest, as the night eating syndrome most likely represents changes in the HPA axis.


Here is another one:

Melatonin Synthesis

Melatonin is the primary substance secreted by the pineal gland, which modulates the adrenal (HPA) axis during clinical illness, the serotonergic system in psychiatric disease, as well as the body's general response to stress.

Melatonin is synthesized within the pineal gland from tryptophan via the pathway shown in the figure above.2 The secretion pattern is generated within the suprachiasmatic nucleus (SCN). Synthesis occurs upon exposure to darkness, with the increased activity of serotonin-N-acetyltransferase. By the action of hydroxyindole-O-methyltransferase (HIOMT), N-acetylserotonin is converted to melatonin. Melatonin is then rapidly secreted into the vascular system and, possibly, into the cerebrospinal fluid.3

Peripheral tissues, such as the retina and the gut, are also known to synthesize melatonin.4


There is the connection with the HPA (above).

This is where our hormone guru, Sharon, comes in with all of her research.

As was found previously, and I find the below very interesting, because it connects ALL of the different phases (RRMS, SPMS, PPMS) of MS together - the one common thread between them all - is the dysfunction/dysregulation of the HPA:

http://www.neurology.org/cgi/content/abstract/53/4/772

Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS

F. Then Bergh, MD, T. Kümpfel, MD, C. Trenkwalder, MD, R. Rupprecht, MD and F. Holsboer, MD, PhD

From the Max Planck Institute of Psychiatry, Neurology, Muenchen, Germany.

Address correspondence and reprint requests to Dr. Florian Then Bergh, Neurologische Klinik, Klinikum Grosshadern, Marchioninistr. 15, D-81377 Muenchen, Germany.

OBJECTIVE: To investigate whether dysregulation of the hypothalamo–pituitary–adrenal (HPA) axis is related to clinical characteristics in MS.

METHODS: The authors performed the combined dexamethasone–corticotropin-releasing hormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subjects. In addition, the short adrenocorticotropic hormone (ACTH) test was performed in 39 consecutive patients. All patients had active disease and none were treated with glucocorticoids, immunosuppressants, or immunomodulators.

RESULTS: The patients had an exaggerated rise in plasma cortisol concentrations in the Dex-CRH test (p < 0.05), indicating hyperactivity of the HPA system. The degree of hyperactivity was moderate in relapsing–remitting MS patients (n = 38; area under the time-course curve for cortisol [AUC-Cort] 226.2 ± 38.9 arbitrary units [AU], mean ± SEM), intermediate in secondary progressive MS patients (n = 16; AUC-Cort, 286.8 ± 60.2 AU), and marked in primary progressive MS patients (n = 6; AUC-Cort, 670.6 ± 148.6 AU). Differences were significant between the three patient groups (p < 0.005), and between control subjects (n = 29; AUC-Cort, 150.8 ± 34.1 AU) and each patient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke’s Expanded Disability Status Scale), but not with the duration of the disease, number of previous relapses, previous corticosteroid treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied.

CONCLUSION: HPA axis hyperactivity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.


For a more technical slant:

Maestroni, G. J. (2001). "The immunotherapeutic potential of melatonin." Expert Opin Investig Drugs 10(3): 467-76.

The interaction between the brain and the immune system is essential for the adaptive response of an organism against environmental challenges. In this context, the pineal neurohormone melatonin (MEL) plays an important role. T-helper cells express G-protein coupled cell membrane MEL receptors and, perhaps, MEL nuclear receptors. Activation of MEL receptors enhances the release of T-helper cell Type 1 (Th1) cytokines, such as gamma-interferon (gamma-IFN) and IL-2, as well as of novel opioid cytokines. MEL has been reported also to enhance the production of IL-1, IL-6 and IL-12 in human monocytes. These mediators may counteract stress-induced immunodepression and other secondary immunodeficiencies and protect mice against lethal viral encephalitis, bacterial diseases and septic shock. Therefore, MEL has interesting immunotherapeutic potential in both viral and bacterial infections. MEL may also influence haemopoiesis either by stimulating haemopoietic cytokines, including opioids, or by directly affecting specific progenitor cells such as pre-B cells, monocytes and NK cells. MEL may thus be used to stimulate the immune response during viral and bacterial infections as well as to strengthen the immune reactivity as a prophylactic procedure. In both mice and cancer patients, the haemopoietic effect of MEL may diminish the toxicity associated with common chemotherapeutic protocols. Through its pro-inflammatory action, MEL may play an adverse role in autoimmune diseases. Rheumatoid arthritis patients have increased nocturnal plasma levels of MEL and their synovial macrophages respond to MEL with an increased production of IL-12 and nitric oxide (NO). In these patients, inhibition of MEL synthesis or use of MEL antagonists might have a therapeutic effect. In other diseases such as multiple sclerosis the role of MEL is controversial. However, the correct therapeutic use of MEL or MEL antagonists should be based on a complete understanding of their mechanism of action. It is not yet clear whether MEL acts only on Th1 cells or also on T-helper Type 2 cells (Th2). This is an important point as the Th1/Th2 balance is of crucial importance in the immune system homeostasis. Furthermore, MEL being the endocrine messenger of darkness, its endogenous synthesis depends on the photoperiod and shows seasonal variations. Similarly, the pharmacological effects of MEL might also be season-dependent. No information is available concerning this point. Therefore, studies are needed to investigate whether the immunotherapeutic effect of MEL changes with the alternating seasons.




Neuroendocrinology. 1997 Apr;65(4):284-90.Links

Corticotropin-releasing hormone inhibits melatonin secretion in healthy volunteers--a potential link to low-melatonin syndrome in depression?

Kellner M, Yassouridis A, Manz B, Steiger A, Holsboer F, Wiedemann K.

Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany. eboll@mpipsyklmpg.de

Interactions between the hypothalamic-pituitary-adrenocortical (HPA) system and melatonin secretion have been demonstrated, but only the effects of melatonin on the activity of the HPA system have been studied in man. Alterations of melatonin secretion described as low-melatonin syndrome have been demonstrated in patients suffering from a major depressive episode, and an inhibitory factor on melatonin secretion has been postulated. We investigated whether corticotropin-releasing hormone (CRH), which is thought to be involved in HPA abnormalities in depressed patients, can also suppress melatonin secretion in healthy volunteers. Ten healthy male human volunteers in a double-blind study design received randomized hourly intravenous injections from 08.00 to 18.00 h that contained 10 micrograms human CRH, 1 microgram adrenocorticotropic hormone (ACTH), or placebo to simulate pulsatile hormone secretion. Plasma melatonin and cortisol responses during the treatment and nocturnal sleep electroencephalograms after the treatment were recorded. Administration of CRH reduced melatonin secretion significantly below values obtained after administration of placebo and ACTH. Cortisol secretion was significantly enhanced by ACTH in comparison to both placebo and CRH. Electroencephalographic sleep parameters revealed no treatment effects. Our findings suggest that CRH has an inhibitory effect on the pineal secretion of melatonin in normal man. A mechanism via a release of cortisol was not supported by our results. Secondary hormonal effects from changes in nocturnal sleep architecture were excluded. Further investigation of the action of CRH on melatonin secretion as well as the mutual feedback between the HPA system and the pineal gland may extend our knowledge of neuroendocrine alterations mediating the adaptive response to stress and the eventual involvement in the pathogenesis of depression.


See why I say that MS might also be able to be called an affective disorder? The pathophysiology and dysfunction that happens in affective disorders is so parallel to what happens pathophysiologically in MS, that it's really bizarre!

And all of the discussions recently and findings being posted lately can all eventually be traced back to the HPA.

And as dignan has shown, there ARE drugs (oral) that can affect any or all of these various dysfunctions.

Interesting..........

Deb
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Postby OddDuck » Thu Jan 26, 2006 6:04 am

And last but not least..........does the HPA affect the immune system and its function? Yep.

Neurol Sci. 2001 Apr;22(2):159-62. Related Articles, Links

Stress, glucocorticoids and the susceptibility to develop autoimmune disorders of the central nervous system.

Morale C, Brouwer J, Testa N, Tirolo C, Barden N, Dijkstra CD, Amor S, Marchetti B.

Neuropharmacology Unit, OASI (IRCCS), Institute for Research and Care on Mental Retardation and Brain Aging, Troina (EN), Italy.

Alterations of the immunoendocrine circuit along the hypothalamic-pituitary-adrenocortical (HPA) axis in various autoimmune diseases have recently been observed, suggesting a modulatory role of this feedback regulation in the pathogenesis of autoimmune diseases. Susceptibility to experimental autoimmune encephalomyelitis (EAE) may be influenced by variations in the production of endogenous glucocorticoid hormones (GC). The adrenocortical response is central to recovery from EAE in the Lewis rat, as reflected by increased severity of the disease in adrenalectomized animals. The key role of GC in modifying the induction and progression of EAE is also emphasized by a reversal of corticoid-mediated effects through treatment with glucocorticoid receptor (GR) antagonists. We studied the relationship between defective GR function and susceptibility to EAE in transgenic (Tg) mice expressing GR antisense RNA. EAE was induced with the encephalitogenic myelin oligodendrocyte peptide (pMOG 36-50) in wild type (Wt) and transgenic (Tg) female mice bearing GR antisense RNA. pMOG 36-50 induced typical EAE in Wt mice but not in Tg mice. Histological examination of brains and spinal cords of Wt mice showed the presence of inflammation and/or demyelination, whereas in Tg mice neither were present. Although the mechanisms underlying the resistance of Tg mice to EAE induction are not yet clarified, compensatory changes at different levels of the HPA-immune axis in response to the potent immunogenic challenge are likely to participate in the observed effects. This work underlies the plasticity of the HPA-immune axis and suggests that pharmacological manipulation of neuroendocrine-immune networks may be a therapy of multiple sclerosis.
PMID: 11603619 [PubMed - indexed for MEDLINE]


I'd like to point out something with regard to most of these abstracts. Has anyone else noticed that the best research findings with regard to MS hasn't been coming from immunology? It's been from the neuropsychiatric field!

What smells fishy here? ARE MS researchers concentrating on the wrong theories?

Deb
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Postby ljm » Fri Jan 27, 2006 9:08 pm

I'm trying to follow this. But one question. If depression is common symptom of MS, wouldn't MS'ers have a higher than average chance of being prescribed antidepressants. And wouldn't that have reduced glutamate and reduced progression (and somewhere, anywhere, been noted or correlated).
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Postby OddDuck » Sat Jan 28, 2006 7:12 am

No, not necessarily. And it's not just any anti-depressant that affects glutamate. Each drug has different mechanisms of action. It is mainly just a couple of the TCAs (as far as anti-depressants go), not the SSRIs (that will produce a strong enough affect on glutamate to be beneficial for MS). It is mainly SSRI anti-depressants that are prescribed to MSers.

Norepinephrine appears to be strongly implicated in the dysfunction of MS, and SSRIs only act on serotonin. TCAs work mainly on norepinephrine and can have strong side-effects.

TCAs are pretty strong and also affect the immune system to a much higher degree than SSRIs, so they are shied away from being prescribed along with any other immunomodulatory drugs.

Plus, the dose of a TCA to affect depression would have to be too high. It is a low dose of a TCA that is effective, which will not really affect depressive states. Catch 22.

Oh...........and since the AEDs also affect mood (they have been found to be mood stabilizers), and the AEDS are commonly prescribed for MSers for the neuro pain, I think fewer MSers are prescribed anti-depressants than you would think.

Deb

EDIT: I made too general of a statement above. SSRIs do act on glutamate receptors, but they are specific receptors. And each SSRI works differently. And I don't believe SSRIs are strong enough to produce any major differences (for MS disease modification). That's why SSRIs are usually prescribed for depression first, i.e. because they are not as strong and are safer to use in combination with other drugs. TCAs also work on glutamate, but also have a much broader spectrum of action. And once again, each TCA works differently than the other.

I have qualified my statement above. I sometimes tend to not explain clearly enough what I am trying to say. Sorry about that.
Last edited by OddDuck on Sat Jan 28, 2006 8:14 am, edited 2 times in total.
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Postby OddDuck » Sat Jan 28, 2006 7:21 am

Plus, as I have speculated before, it would also take more than just affecting glutamate ALONE in order to show benefit for MS.

You have to do several things at once - affect several other pathophysiologies at the same time, not just reduce glutamate alone and then expect to see improvement.

Deb

EDIT: Glutamate (along with GABA) is also strongly implicated in the mental diseases of schizophrenia and bi-polar, so it's a complex menagerie!
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