Wednesday, January 27, 2010

When the Brain Is Hungry For Cholesterol

by Chris Masterjohn

Those of you who have spent much time perusing my web site know that cholesterol is the limiting factor for the formation of synapses, connections between neurons that form the basis of learning and memory. In fact, one of the reasons we learn better when we get enough sleep is because the brain ramps up its production of cholesterol when we're getting our shut-eye.

Scientists have long thought that cholesterol in the plasma never enters the brain in significant amounts because its transport is blocked by the blood-brain barrier. In general, the brain produces its own cholesterol and, when that cholesterol's time is up the brain converts it to 24-hydroxy-cholesterol and sends it out with the trash.

An article in
February's issue of Current Opinion in Lipidology, however, reviews two recent studies published last year showing that when the brain fails to make enough of its own cholesterol, it does in fact take it from the bloodstream.

In one study, researchers inactivated the gene for squalene synthase, the first enzyme committed to
cholesterol synthesis, from the cells in the ventricular zone of the brains of mice. Progenitor cells in this region began producing new blood vessels that allowed them to acquire cholesterol from the bloodstream or from the neural tube.

In the other study, researchers inactivated a cholesterol transporter in glial cells. Glial cells support neurons in a variety of ways — one of them is to produce secretions rich in the
cholesterol necessary for synapse formation. The brains of these mice partly made up for the resulting cholesterol deficiency by taking up more cholesterol esters from HDL particles in the bloodstream.

This concept, that when cholesterol made in the brain proves insufficient to meet the brain's needs the brain can compensate by taking cholesterol from the blood, goes a long way in explaining why all of the mental problems suffered by Smith-Lemli-Opitz Syndrome (SLOS) patients improve with dietary cholesterol. In fact, the FDA has even approved a pharmaceutical-grade cholesterol supplement to improve the retardation, hyperactivity, irritability, poor attention span, and tendency toward aggressive and self-injuring behavior seen in these children. 

These findings are truly remarkable, because they open up the possibility that cholesterol in the bloodstream may support the brain in much less extreme cases of cholesterol deficiency and in many other undiscovered ways.

Read more about the author, Chris Masterjohn, PhD, here.

10 comments:

  1. "a pharmaceutical-grade cholesterol supplement"

    After decades of being told that cholesterol is the worst thing since sliced bread, that sounds hilarious.

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  2. Haha, "the worst thing since sliced bread!" An appropriate rendition of the phrase. :-)

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  3. Dear Good Chris Masterjohn, I love your powerful critique of "The China Study" That's where I first came across your spectacular ideas. I finished reading Taubes’ GCBC on June 16, 2008 (I have retained the date in my memory, because I KNEW it was a paradigm changer) and my life has been transformed for the better since then. A new book recommendation for you. “The Other Brain” by R. Douglas Fields, PhD. It’s about the 85% of the cells in our brains that aren’t neurons, but glial cells. Our brains are FATTY and CHOLESTEROLLY. Glia and axons are fatty fat fat fat fat fat fatty fat-hyperlipidinous (my coined word). Axons extend into the body too. All 100,000 miles of them if they were stretched out and laid end to end- that's a lot of FAT. I just got the book. Can’t put it down, except to comment here. This may be preaching to the choir, but advising humans to eat low-fat, vegetarian is a prescription for brain deterioration and dumb-down. HAND ME THE LARD and the BEEF. I am LIVID that I hadn’t heard about any of this until Taubes’s book fell into my hands, and I teach biochemistry for heaven’s sake! Another phrase of mine, Wheat is Murder (ala Lierre Keith).

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  4. And perhaps this explains the reason that us older folks with higher cholesterol than the mainstream medical would like us to have live longer with a better quality of life.

    No statins for me!!!! I love my cholesterol....especially my large fluffy kind.

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  5. I'm trying to get my hands on this fabled pharmaceutical-grade cholesterol... can't locate it on the interweb. Any resources for it? ~Thanks.

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  6. Chris:

    This is related to Dexter's comment.

    Do you think that it is possible that the gradual increase in cholesterol that we often see with age is in fact an evolutionary response to combat senescence?

    Also, I have seen research suggesting that caloric restriction may lead to accelerated senescence, but I do not recall any mention of cholesterol. Maybe this new article you reviewed provides the answer.

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  7. I mentioned I'm reading 'The Other Brain' by Dr. R. Douglas Fields, Fascinating. I just found his mention of cholesterol being required for creation of synapses and another connection between infection with Chlamydia being the catalyst to Alzheimer's. James Le Fanu in 'The Rise and Fall of Modern Medicine" pointed out the link between heart disease and chlamydia-interesting, references available upon request. Don't lower cholesterol and impair the immune system PLEASE. And then there's this...
      I started ruminating on the fact that there is a blood-gut barrier (tight junction control and regulation between the intestine and blood) that is made leaky by gluten. This is problematic to say the least. So I wondered about gluten and the blood-brain barrier and sure enough there is some speculation about this by a Jeremy E. Kaslow, M.D. My interest is peaked for several reasons. I recently heard about non-celiac gluten sensitivity and that you don't have to be diagnosed with celiac to have problems. Combine that with Lierre Keith of 'The Vegetarian Myth' alerting me to the fact that grains are addicting because of the opioid recepters they activate in the brain (reference for this too if you'ld like). AND then there's this... we have NO requirement in human nutrition for grain and wheat....zero, zip, nada. Humans are adapted to eat grains in one and only one spectacular way.....it helps us (and has helped us for a very long time) reproduce like mad. The more we've reproduced, the more people there have been; the more chance for genius. Up until about 100 years ago, natural forces kept our population in check.
    So what havoc might gluten pose in the brain (even for non-celiacs)?. From Dr. Kaslow....

    "Another factor is related to the concept “cerebral allergy.”  This is a concept supported by just a few hundred medical doctors and psychiatrists. It became increasingly apparent in the 1990s that there are immune system defenses in the brain, and that the microglia can be recruited and even reprogrammed to do the work. Experiments show that microglia can be stimulated to “change roles” and produce a cascade of cytokines (the “cell-movers”) that can produce, maintain and increase the inflammation response. Because we cannot feel brain tissue - it is not “engineered” to signal to us its own changes - hence there is no pain, itching, etc. Inflammation involves swelling, increased blood flow, increased temperature, itching or pain or both - none of this can be felt in the brain unless severe. This must be one of the strongest reasons for people with brain-based disorders denying that anything is wrong with their brains."
    Autoimmunity, inflammation, neurodegeneration, mental illness .....hmmm.
      Anyway, I'm starting to see that the idea of an inviolable (to mischievous gluten) blood-brain barrier is a dangerous assumption.

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  9. "In fact, one of the reasons we learn better when we get enough sleep is because the brain ramps up its production of cholesterol when we're getting our shut-eye."

    lol, now I have an excuse to lie in bed even more tomorrow morning, it's helping my brain! I have proof lol

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  10. This comment has been removed by the author.

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