Epilepsy Talk
Science Daily: Glucosamine dampens the brain hyperexcitability seen in seizures or epilepsy | March 15, 2018
Researchers have found that inducing a biochemical alteration in brain proteins via the dietary supplement glucosamine was able to rapidly dampen that pathological hyperexcitability in rat and mouse models.
These results represent a potentially novel therapeutic target for the treatment of seizure disorders, and they show the need to better understand the physiology underlying these neural and brain circuit changes.
Seizure disorders — including epilepsy — are associated with pathological hyperexcitability in brain neurons.
Unfortunately, there are limited available treatments that can prevent this hyperexcitability.
However, University of Alabama at Birmingham researchers have found that inducing a biochemical alteration in brain proteins via the dietary supplement glucosamine was able to rapidly dampen that pathological hyperexcitability in rat and mouse models.
These results represent a potentially novel therapeutic target for the treatment of seizure disorders, and they show the need to better understand the physiology underlying these neural and brain circuit changes.
Proteins are the workhorses of living cells, and their activities are tightly and rapidly regulated in responses to changing conditions.
Adding or removing a phosphoryl group to proteins is a well-known regulator for many proteins, and it is estimated that human proteins may have as many as 230,000 sites for phosphorylation.
A lesser-known regulation comes from the addition or removal of N-acetylglucosamine to proteins, which is usually controlled by glucose, the primary fuel for neurons.
Several years ago, neuroscientist Lori McMahon, Ph.D., professor of cell, developmental and integrative biology at UAB, found out from her colleague John Chatham, D.Phil., a UAB professor of pathology and a cardiac physiologist, that brain cells had the second-highest amounts of proteins with N-acetylglucosamine, or O-GlcNAcylation, in the body.
At the time, very little was known about how O-GlcNAcylation might affect brain function, so McMahon and Chatham started working together.
In 2014, McMahon and Chatham, in a study led by graduate student Erica Taylor and colleagues, reported that acute increases in protein O-GlcNAcylation caused long-term synaptic depression, a reduction in neuronal synaptic strength, in the hippocampus of the brain.
This was the first time acute changes in O-GlcNAcylation of neuronal proteins were shown to directly change synaptic function.
Since neural excitability in the hippocampus is a key feature of seizures and epilepsy, they hypothesized that acutely increasing protein O-GlcNAcylation might dampen the pathological hyperexcitability associated with these brain disorders.
That turned out to be the case, as reported in the Journal of Neuroscience study, “Acute increases in protein O-GlcNAcylation dampen epileptiform activity in hippocampus.”
The study was led by corresponding author McMahon and first author Luke Stewart, a doctoral student in the Neuroscience Theme of the Graduate Biomedical Sciences Program. Stewart is co-mentored by McMahon and Chatham.
“Our findings support the conclusion that protein O-GlcNAcylation is a regulator of neuronal excitability, and it represents a promising target for further research on seizure disorder therapeutics,” they wrote in their research significance statement.
The researchers caution that the mechanism underlying the dampening is likely to be complex.
Research details
Glucose, the major fuel for neurons, also controls the levels of protein O-GlcNAcylation on proteins.
However, high levels of the dietary supplement glucosamine, or an inhibitor of the enzyme that removes O-GlcNAcylation, leads to rapid increases in O-GlcNAc levels.
In experiments with hippocampal brain slices treated to induce a stable and ongoing hyperexcitability, UAB researchers found that an acute increase in protein O-GlcNAcylation significantly decreased the sudden bursts of electrical activity known as epileptiform activity in area CA1 of the hippocampus.
An increased protein O-GlcNAcylation in normal cells also protected against a later induction of drug-induced hyperexcitability.
The effects were seen in slices treated with both glucosamine and an inhibitor of the enzyme that removes O-GlcNAc groups.
They also found that treatment with glucosamine alone for as short a time as 10 minutes was able to dampen ongoing drug-induced hyperexcitability.
In common with the long-term synaptic depression provoked by increased O-GlcNAcylation, the dampening of hyperexcitability required the GluA2 subunit of the AMPA receptor, which is a glutamate-gated ion channel responsible for fast synaptic transmission in the brain.
This finding suggested a conserved mechanism for the two changes provoked by increased O-GlcNAcylation — synaptic depression and dampening of hyperexcitability.
The researchers also found that the spontaneous firing of pyramidal neurons in another region of hippocampus, area CA3, was reduced by increased O-GlcNAcylation in normal brain slices and in slices with drug-induced hyperexcitability.
This reduction in spontaneous firing of CA3 pyramidal neurons likely contributes to decreased hyperexcitability in area CA1 since the CA3 neurons directly excite those in CA1.
Similar to the findings for brain slices, mice that were treated to increase O-GlcNAcylation before getting drug-induced hyperexcitability had fewer of the brain activity spikes associated with epilepsy that are called interictal spikes.
Several drug-induced hyperexcitable mice had convulsive seizures during the experiments — this occurred in both the increased O-GlcNAcylation mice and the control mice.
Brain activity during the seizures differed between these two groups: The peak power of the brain activity for the mice with increased O-GlcNAcylation occurred at a lower frequency, as compared with the control mice.
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Materials provided by University of Alabama at Birmingham. Note: Content may be edited for style and length.
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Epilepsy Talk 
It seems like there are a couple of ways to get more glucosamine into your diet. One is eating pounds of crustacean shells or getting a supplement synthesized from such shells. The other is being sure to get some collagen in your diet. This can come from bone broths, bone marrow, or collagen rich dishes such as oxtail soup. There are also collagen protein powder supplements available.
https://hubpages.com/health/Foods-that-contain-glucosamine
Interesting info. Thanks.
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Comment by paleobird — March 15, 2018 @ 5:08 PM
Thanks for your suggestions paleobird.
The page you referenced is very cool, but I think I’ll stick to the supplements! 🙂
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Comment by Phylis Feiner Johnson — March 15, 2018 @ 8:51 PM
I have read this article pretty close & it made me think what I learned today from a herbalist where I tested 2 GABA supplements. It was interesting how I tested the 2 GABA products as I am now convinced that GABA helps the levels of GLUTAMATE stay at a normal brain level, whereas if GABA levels are low, like I believe mine are, the GLUTAMATE will rule my brain over the serotonin, dopamine & other chemicals of excititory neurotransmitter getting more agressive over the inhibitory nerve endings, cells & neurotransmitters not able to stay calm thanks to GLUTAMATE SATURATION in the brain. So how is it that GABAPENTIN that was suppose to keep GABA stable in the brains of humans, is now today according to my pharmacist tells me it only helps for pain conditions like neuropathy, fibromyalgia, but not for Epilepsy anymore ? GABA can also keep the levels of glucose in the brain stable, and yet no tests for GABA or GLUTAMIC ACID can get done at most neurologist offices. Instead we are told we need VNS, BNS or brain surgery, with out doing simple blood work before all things are ruled out for surgery BNS or VNS to be the next best thing to do. Not no surprise that glucosamine can work in rats, as we are always compared to a rat or a guinea pig, What’s new ?
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Comment by C D — March 15, 2018 @ 10:09 PM
I had you in mind when I posted this article C D. 🙂
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Comment by Phylis Feiner Johnson — March 16, 2018 @ 8:33 AM
Does this mean that a hypoglycemic persons seziures can be affected by their blood sugar levels?
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Comment by Jeanine Bunt — March 15, 2018 @ 11:33 PM
Hypoglycemia — Also called low blood glucose, is a condition that occurs when one’s blood glucose is lower than normal, usually below 70 mg/dL.
Signs include hunger, nervousness, shakiness, perspiration, dizziness or light-headedness, sleepiness, and confusion.
Glucose, an important source of energy for the body, comes from food.
Carbohydrates are the main dietary source of glucose.
Rice, potatoes, bread, tortillas, cereal, milk, fruit, and sweets are all carbohydrate-rich foods.
After a meal, glucose is absorbed into the bloodstream and carried to the body’s cells.
Insulin, a hormone made by the pancreas, helps the cells use glucose for energy.
If a person takes in more glucose than the body needs at the time, the body stores the extra glucose in the liver and muscles in a form called glycogen.
The body can use glycogen for energy between meals.
Extra glucose can also be changed to fat and stored in fat cells. Fat can also be used for energy.
Hypoglycemia can happen suddenly.
It is usually mild and can be treated quickly and easily by eating or drinking a small amount of glucose-rich food.
If left untreated, hypoglycemia can get worse and cause confusion, clumsiness, or fainting.
Severe hypoglycemia can lead to seizures, coma, and even death.
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Comment by Phylis Feiner Johnson — March 16, 2018 @ 8:51 AM
Phyllis, I started using a collagen protein powder supplement just for its ability to make my fingernails grow long and strong. I have noticed that I also am sleeping better since taking it (my seizure disorder is nocturnal). I figured that it might be that I was just a bit protein deficient but perhaps it was the glucosamine.
No, I don’t feel like eating piles of shrimp shells either but I love gelatinous types of meat dishes such as osso bucco and oxtail soup. Bone marrow is delectable too.
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Comment by paleobird — March 16, 2018 @ 12:28 AM
I’ll skip the osso bucco and oxtail soup. But biotin also helps with both nail growth and also hair growth.
The protein supplement is definitely great. I take it too and feel more energetic and balanced.
Thanks again for your brilliant insights. 🙂
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Comment by Phylis Feiner Johnson — March 16, 2018 @ 8:43 AM
Hi Phyllis,
I’m a vegan, so I can’t go down the bone broth/oxtail route. In a nut shell, is it as easy as taking a daily glucosamine supplement?
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Comment by Anna Hargreaves — March 16, 2018 @ 4:32 AM
Yes. I would suggest the glucosamine supplement.
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Comment by Phylis Feiner Johnson — March 16, 2018 @ 8:32 AM
Anna, as long as you are OK with taking a supplement synthesized from the exoskeletons of crustaceans but are not OK with taking a supplement synthesized from the endoskeletons of mammals or chickens……
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Comment by paleobird — March 16, 2018 @ 4:14 PM
Sorry, I’m not sure what you mean
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Comment by Anna Hargreaves — March 16, 2018 @ 4:34 PM
The synthetic glucosamine supplements come from shrimp shells so I’m not sure if that is contrary to your vegan principles. There is no truly vegan option for you here. Just more evidence, IMO, that veganism is not healthy in the long run as there are multiple nutrient deficiencies waiting for you if you are very strict with not wanting any shrimp to die for your health. Glucosamine as well as B12 and many other nutrients just don’t come from plants in meaningful quantities that we can absorb. We are naturally omnivores and trying to force our bodies into being herbivores just doesn’t work.
I highly recommend Lierre Kieth’s excellent book, “The Vegetarian Myth” for anyone who thinks they are saving the planet by not eating meat.
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Comment by paleobird — March 16, 2018 @ 9:13 PM
Whilst I appreciate your dietary comments paliobird, I was really just interested in wether or not it was helpful for me to take glucosamine as a positive step for my nocturnal seizures. As a matter of interest to yourself, I take Vitamin B12 supplements and eat plenty of Marmite and fortified cereals. I have been on a plant based diet since last November, and can honestly say that I have never felt healthier. I haven’t had any coughs or colds over the winter, which is unusual for me, and no days off work. I have lost a stone in weight without trying (which I needed to do), my cravings for sugar has gone, and I have more energy than I’ve had in years. The decision as to wether or not I take glucosamine will be purely based on its likely effectiveness on my condition, and it will be my decision alone if I can live with the fact that it is derived from the shells of crustaceans.
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Comment by Anna Hargreaves — March 17, 2018 @ 6:16 AM
How much glocosamine and how often are people taking the supplement 2x or 3x day?
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Comment by Cindy — March 17, 2018 @ 11:47 AM
To supplement glucosamine, take 300 – 500 mg, three times a day, for a total daily dose of 900 – 1,500 mg.
The benefits of glucosamine are dose-dependent, and studies use up to 2,000 – 3,000 mg a day, taken in several doses.
https://examine.com/supplements/glucosamine/
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Comment by Phylis Feiner Johnson — March 17, 2018 @ 1:12 PM
Does it have to be pure Glucosamine? I have Spring Valley’s Glucosamine Sulfate in 1000mg; I take it once a day for my shoulders. Glucosamine Sulfate is much less expensive.
Ps It really helps joint pain
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Comment by Leica Roberts — March 23, 2018 @ 9:04 AM
Glucosamine Sulfate is great. The best of both worlds.
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Comment by Phylis Feiner Johnson — March 23, 2018 @ 10:19 AM