Friday, 26 May 2017

GABA controls oligodendrocytes

Hamilton NB, Clarke LE, Arancibia-Carcamo IL, Kougioumtzidou E, Matthey M, Káradóttir R, Whiteley L, Bergersen LH, Richardson WD, Attwell D. Endogenous GABA controls oligodendrocyte lineage cell number, myelination, and CNS internode length. Glia. 2017;65(2):309-321

Adjusting the thickness and internodal length of the myelin sheath is a mechanism for tuning the conduction velocity of axons to match computational needs. Interactions between oligodendrocyte precursor cells (OPCs) and developing axons regulate the formation of myelin around axons. We now show, using organotypic cerebral cortex slices from mice expressing eGFP in Sox10-positive oligodendrocytes, that endogenously released GABA, acting on GABAA receptors, greatly reduces the number of oligodendrocyte lineage cells. The decrease in oligodendrocyte number correlates with a reduction in the amount of myelination but also an increase in internode length, a parameter previously thought to be set by the axon diameter or to be a property intrinsic to oligodendrocytes. Importantly, while TTX block of neuronal activity had no effect on oligodendrocyte lineage cell number when applied alone, it was able to completely abolish the effect of blocking GABAA receptors, suggesting that control of myelination by endogenous GABA may require a permissive factor to be released from axons. In contrast, block of AMPA/KA receptors had no effect on oligodendrocyte lineage cell number or myelination. These results imply that, during development, GABA can act as a local environmental cue to control myelination and thus influence the conduction velocity of action potentials within the CNS.


GABA is the major inhibitory neurotransmitter and blocks signals from excitatory nerves such as glutamate. A few years ago, it was found that oligodendrocyte precursors have glutamate receptors and when these get stimulated it probably acts as a signal to the oligodendrocyte precursor cells to change into an oligodendrocyte and to start myelination. The glutamate is essentially a calcium channel making the inside of the  cell more electrically positive. however blocking this made no infuence on cell numbers. However, if you stimulate with GABA A which is a chloride channel meaning the inside becomes more electrically negative you get less oligos and less myelination. Is there any evidence that benzodiazepines block or stimulate myelination ?  Don't think so, but have people looked ?. 

5 comments:

  1. They say that Gaba is inhibitory of OPC´s and myelination?
    "Blocking the effects of
    GABA on GABAA receptors nearly doubled the number of
    oligodendrocyte lineage cells (Fig. 2A,B), increased myelination
    (Fig. 4G,H) and decreased internode length (Fig. 5G,H)"
    You dont thing so?
    Luis

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  2. Would this mean gabapentin/Neurontin and pregabalin/Lyrica would make MS worse? These drugs are commonly used for neuropathic pain in MS patients. I have seen some recent study that seemed to verify that these drugs block formation of new synapses and reduce potential for neuroplasticity.

    One would think that these drugs, by making an axon less positive through opening chloride channels, would be neuroprotective?

    Neuroprotection should occur by increasing chloride in cell or blocking Ca or Na thereby blocking apoptosis of the neuron? It seems that blocking glutamate does not work (Ca channels), increasing chloride does not work. Here to hoping that blocking Na channels with carbamezipine, dilantin or valproic acid works. Correct me if I am wrong MD.

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    Replies
    1. I agree with you I expect neuroprotection.

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  3. I had already read some studies pointing out that GABA would block the medullar remyelination, I will see if I find this study again. And after reading it, I was very worried at the time because I used Gabapentin when I felt neuropathic pain (which, although good, decreased considerably).
    Now that study has left me a bit confused. So would gabapentin have any effect of inhibiting remyelination, or not? I was wondering this because as far as I read Gabapentin does not bind to GABA A or GABA B, it also does not interfere in the production or uptake of GABA, although its structure is similar to GABA, so my doubt. And then would not Riluzol have any positive effect on remyelination?

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  4. I posted on this one as you want to hear about myelination but I see it has caused confusion because it sends a negative message for people using GABA stimulators,

    However this aspect was not shown and it may never happen. It is a theorectically and the opposite may be occurring. I will post on this to balance the negativity.

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