An Antiglutamatergic Drug Prevents Foggy Brain Of Old Age

Discussion in 'Articles' started by haidut, Dec 23, 2014.

  1. haidut

    haidut Member

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    I don't see a reason why it would not be helpful for all cases of foggy brain, not just in the elderly, considering Ray has written that the excitotoxicity by glutamate is behind many brain conditions including depression. A natural alternative would be the amino acid theanine and/or magnesium, probably best taken as a combo.

    http://www.eurekalert.org/pub_releases/ ... 122214.php
     
  2. Lin

    Lin Member

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    I wonder how much green tea it would take... How much Mg bicarbonate?
     
  3. OP
    haidut

    haidut Member

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    The studies on theanine I posted showed very good results from 400mg-600mg a day for reducing serotonin and increasing dopamine. There are some human studies on depression/dementia showing results with 150mg-300mg magnesium daily. Obviously the exact dosage will have to derived experimentally for each person.
     
  4. aguilaroja

    aguilaroja Member

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    I share the concerns about glutamine, and regard for theanine and magnesium as supports. However, the article does not seem to say that exclusively anti-glutamatergic action by riluzole prevents hippocampal-dependent age-related cognitive decline.

    Pereira and colleagues assert that increased synaptic glutamatergic activity by riluzole, more "focused" at the synapse, occurs . It may be possible that glutamine "spillover" is a major factor in decline, but this question is raised but not answered in the study. Riluzole has other actions in addition to affect glutamine transport.

    http://www.ncbi.nlm.nih.gov/pubmed/25512503

    Proc Natl Acad Sci U S A. 2014 Dec 15. pii: 201421285. [Epub ahead of print]
    Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering.
    Pereira AC1, Lambert HK2, Grossman YS3, Dumitriu D3, Waldman R4, Jannetty SK2, Calakos K2, Janssen WG4, McEwen BS1, Morrison JH5.

    "Our clustering results also reinforce previous studies finding that the glutamate modulator riluzole likely increases synaptic glutamatergic activity (22, 23). The key mechanism of action of riluzole to prevent aging may well be the increase of glutamate uptake by glia transporters (19–21), correcting their decreased function that occurs with aging (14, 16, 17). Previous work has shown age-related partial rescue of a hippocampal glutamate transporter expression and spatial memory with riluzole treatment (15). By maintaining tighter control of glutamate levels at the synapse and rapid cycling of glutamate-glutamine (22), synaptic glutamatergic activity may be increased while preventing glutamate overflow and activation of extrasynaptic NMDA receptors. Other mechanisms induced by riluzole could also be involved in the prevention of age-related cognitive decline, including increased BDNF expression (25) and oxidative metabolism(24). Future experiments could individually block each of these pathways (i.e., hippocampal infusion of glutamate transport inhibitors, use of BDNF antibody) to investigate which one(s) block the effect on behavior, further pinpointing the critical pathways."


    http://en.wikipedia.org/wiki/Riluzole

    "Mechanism
    Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons.[10][11] Riluzole has also been reported to directly inhibit the kainate and NMDA receptors.[12] However, the action of riluzole on glutamate receptors has been controversial, as no binding of the drug to any known sites has been shown for them.[13][14] In addition, as its antiglutamatergic action is still detectable in the presence of sodium channel blockers, it is also uncertain whether or not it acts via this way. Rather, its ability to stimulate glutamate uptake seems to mediate many of its effects.[15][16] In addition to its role in accelerating glutamate clearance from the synapse, Riluzole may also prevent glutamate release from presynaptic terminals.[17] These effects combined could significantly reduce glutamate signaling and cause indirect antagonism without acting at glutamate receptors themselves."
     
  5. OP
    haidut

    haidut Member

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    Hhmmm, I am pretty sure when I first read the article it said pretty much what my post title says - "an antiglutamatergic drug...". I wonder if someone contacted the article authors and pointed out the same issue as aguilaroja did and they changed it...
    I didn't mean to imply that simple reductions of glutamine is the only mechanism of action.
     
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