Spine Inflammation Might Explain Why Motor Neurons Die in ALS, Researchers Suggest

Spine Inflammation Might Explain Why Motor Neurons Die in ALS, Researchers Suggest

Inflammation in the spinal cord, at least in part mediated by a molecule called PGE2, likely contributes to the disease processes of amyotrophic lateral sclerosis (ALS), researchers from Nihon University in Japan suggest.

Their study, published in the journal Neurochemistry International, suggests that the molecule signals through one of its four receptors to drive the disease, which is increased in motor neurons of animal models early in ALS.

This inflammation, they argue, might worsen neuron damage in ALS and explain why motor neurons are more sensitive to the disease than other nerve cells.

To reach this conclusion, the study, “Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice,” used both a mouse model of ALS and lab-grown cells to study the factor.

Earlier studies had indicated that PGE2, or prostaglandin E2, is involved in ALS, as the molecule is found in abnormally high levels in brain tissue, cerebrospinal fluid, and blood serum from patients with sporadic ALS.

But the team wanted to find out which of the four receptors for PGE2, named EP1 to EP4, was at work in the disease. Earlier studies had indicated that PGE2, signaling through EP2 and EP3 in glial cells in the brain and spinal cord, contribute to cell death. So this time, the team took a closer look at neurons.

They found that the EP2 receptor was found in larger numbers in motor neurons of ALS mice in early stages of their disease. When the mice were 11 weeks old — an age at which they had not yet started showing symptoms — they had more EP2 receptors than healthy mice. By 15 weeks, when they start showing ALS symptoms, the numbers were even higher.

The EP3 receptor was not affected by the disease and researchers found it in similar numbers in ALS and healthy mice at both time points.

Using lab-grown motor neuron-like cells, the team further showed that PGE2 signaling triggered cell death and boosted the production of the EP2 receptor, making cells even more susceptible to cell death through the signaling of PGE2.


  1. Karen says:

    I have been telling the neurologist that it hurts in my spinal cord/column for 4 years and they have never taken a test of the spinal fluid, this just validates my idea that something is wrong in the spinal column. This makes me angry for not being listened to.

    • Charlie says:

      Taking a spinal fluid sample during the diagnosis period for ALS is normal. The bad news is that if the sample is clear and sparklingly healthy we are one step further towards a confirmation of ALS. It would be normal to hope that something unwelcome and unpleasant is found in the sample so that ALS is ruled out.

  2. Charlie says:

    It would be very helpful if this article showed how this information on the EP2 Receptor could be used to formulate a inhibition of the signalling…assuming of course that researchers feel that inhibiting the signals is the way to go….and if it isn’t the way to go, then how might they develop this.
    Otherwise this interesting knowledge is simply ‘symptom recognition.’

    • Magdalena Kegel says:

      Hi Charlie,
      Thanks for your comment. Research is often a slow and stepwise process. In the current study, researchers found that the EP2 receptor is involved in the inflammation in ALS. Rather than “symptom recognition” this is a crucial bit of information in the puzzle of the disease processes of the condition.

      It might be possible that they are looking into if inhibiting the signal is a potential treatment option in ALS — results that might be published in the future. But at this moment, they chose to share their research insights in the present form. By publishing this information, the researchers allow other scientists in on the quest to understand the disease and search for new ways to treat ALS.

      • Charlie says:

        ‘Research is often a slow and stepwise process.’
        Research is ALWAYS like that…and none of us are getting any better.

      • Charlie says:

        Well, let’s hope those other researchers step in. I have not heard about any doing so. I have not heard about these researchers working on signal inhibition either. Have you? Have you?
        Your connections with Nihon Uni. are almost certainly better than mine, as mine are non-existant……

  3. Charlie says:

    I regret to inform ALS News Today that I maintain my view that ALS research is currently stuck in the groove of ‘symptom recognition.’ I can prove it too. It’s like this…add up the number of times per month you see here and elsewhere that ‘x’ ‘could be’ ‘might be’ ‘is possibly’ connected with ALS. I have to be realistic and say that research is scatter-gun’ and must be happening such that someone hopes to trip over a treatment/cure by serendipitous accident eg as Fleming tripped over penicillin.

    Research is not focused. it examines a multitude of possibilities and that tells me that researchers do not know where best to focus their efforts.

  4. Mary Ellen Fitzpatrick Dennard says:

    My neurologist ordered a spinal fluid test. MS was ruled out, so only ALS was left. I was sent to an ALS specialist neurologist, and had the needle in your muscle EKG set of tests. It was insanely painful. If I ever do this test again, I’ll get a sedative. But this test did the trick, and I was finally (4 years of ALS-like complaints) diagnosed. No known cause, no effective treatment, extreme fatigue, no cure, and fatal; probably by pneumonia.
    This really stinks. I try to keep a positive attitude, but sometimes ALS really gets me down, especially if I have just lost another function.

  5. Julio says:

    I guess this finding would help explain why the eye motor neurons are resistant to the disease, but I’m no expert?

      • Jerod Edgington says:

        I have not been diagnosed but am dealing w/ a myriad of ALS type symptoms and one that is not normally mentioned but I have experienced is a sudden decrease in my visual acuity. Is this more common than thought?

        • Strange says:

          I am in year 3 of symptomes , but not diagnosed , has been told that ” You Were dead by now if it Was ALS , pain is not ALS , but i Can se others that have had symptomes for several years before diagnoses, it is extremly hard not to know what is Wrong When You get more and more symptomes . Hope for a cure and a biomarker.

          • Karen says:

            I’m in the same boat going on 9 years now. I am angry at this point and losing more functions all the time. Don’t believe them when they say no pain, there is tremendous pain for me.

          • Jerod Edgington says:

            The pain I’m experiencing and the lethargy are insane. So much so that I’m hardly able to function even remotely like a normal human. This is maddening.

          • Jerod Edgington says:

            You are so right Strange, I’m sorry to hear you have been dealing with symptoms for such a long time. The not knowing is the hardest part by far. I’m exhausted after dealing with it for 6 months. I’ve been to more Dr’s appointments than I can count at this point after never have been for a single visit since I was a very young child for basic checkups. I’ll be on visit #4 to the Neuro late August. It’s agony for sure.

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