Your Memory Is In Your Blood

I was two thirds of the way to the end of a 45 member circle at a workshop, hating my position in the line-up. The facilitator started an introduction exercise that involved reciting the names of preceding individuals -from the beginning. The room was filled with science types, many commenting on the cognitive process of memory. As the people before me went, I concentrated on the names, faces and associating ideas with them. Dawn had an image of the rising sun behind her dark hair and Robin's pale blue blouse was like an egg.

The blood flowing through our veins is packed with cells -one type, platelets are small things. I imagine they're slightly squishy like a ball not quite taught with air but with the texture of a basket ball -the bumps representing lipids. In the living balls, the lipids constantly exchange, replacing each other. The enzyme responsible, phospholipase A2 (PLA2), may play a role in memory.

PLA2 is not just in the tiny platelet cells; it's in a variety of other cell types including neurons. In the brains of victims with memory deficits, PLA2 activity is decreased. With the idea that the PLA2 activity in platelets reflects that of brain cells, researchers at the University of Sao Paulo in Brazil asked whether brain training exercises could increase the activity of this enzyme in healthy elderly subjects.

The tasks researchers gave the subjects included a list recall exercise, much like the name task that I so dreaded. The experimental group was “trained” in four 90 minute sessions that included a discussion regarding memory and aging and a practice component that introduced the concept of mnemonic strategies (associating words with related meanings).

Blood was taken at the outset of the experiment and when it was over two weeks later. Researchers tested for PLA2 activity... it changed, generally increasing with the exercise. One caveat: there are several types of the enzyme. Some of them stay in the cell, while others are secreted. One of them depends on calcium and another is calcium independent. This last one, calcium-independent PLA2, decreases in patients with Alzheimer's disease. This one, however, also decreased in healthy individuals that underwent the training.

The paper concludes “the present data support the notion that cognitive training promotes biochemical changes that correlate with memory acquisition and retrieval... and illustrates the potential of non-pharmacological intervention to improve cognition in older adults through the modification of neurobiological systems.” So, learning can change your brain chemistry. And this change is likely paralleled in your blood.

With the mentioned caveat, I wrote to Dr. Wagner Gattaz, lead investigator of the study. Here is his reply:

I am also confused by this increment in iPLA2, I would expect exactly the contrary. I can not explain it. Therefore, the conclusion from our data is that cognitive training causes changes in membrane phospholiopid metabolism, in a very general manner.

1. Cognitive activity through the life, as measured by years of school, reduce the risk for AD. This is one of the most consistent findings across several studies.
2. PLA2 is low in AD
3. Cognitive activity increased PLA2
4. Thus, this finding (3) may provide a biological rationale for (1)
5. Maybe the use of cognitive training should be emphasized in individuals at risk for AD.

We are now investigating the effects of cognitive training on PLA2 in patients with AD. Our question to be tested: does the enzyme activity also increase in these patients?

After doing the naming exercise, I would love to have access to my own PLA2 levels and how they change over the course of the task, or better yet, a lifetime. Undertaking research on brain lipid biochemistry in people and trying to relate it to blood chemistry is quite the cognitive task. I wonder what Dr. Gattaz's PLA2 activity is.

TALIB, L., YASSUDA, M., ODINIZ, B., FORLENZA, O., GATTAZ, W. (2008). Cognitive training increases platelet PLA2 activity in healthy elderly subjects. Prostaglandins, Leukotrienes and Essential Fatty Acids DOI: 10.1016/j.plefa.2008.03.002

Spicing Up Mouse Muscles: Potential Therapy for Muscular Dystrophy

Preparing meat with turmeric occurs in kitchens daily but using spices to treat muscle disease is not a common occurrence. New research from Nanjing University in China shows curcumin, the compound in turmeric responsible for its yellow hue, alleviates a mouse version of muscular dystrophy (mdx) when injected.

Duchenne's muscular dystrophy is a muscle wasting disease that results in severe disability and ultimately, death. What is striking about the article published in Molecules and Cells is that the pathology of the muscle fibers is largely prevented.

In my research with potassium channels, I spent some time viewing plump dystrophic mouse muscles under the microscope. Normal muscle slices easily, folding onto the slide; cross sections show uniform fibers nicely packed with nuclei in the cell's corners. Muscles from mdx mice, conversely, fragment and shred during the cutting process. The muscle integrity is drastically compromised and that's noticeable even when you get a nice sample laying flat on the slide. Debris is packed between the misshapen fibers and the nuclei no longer associate with the edge of the cell but are now centralized.

The figures in this study are impressive because the muscle fibers appear healthier and the mice regain strength. The mouse data looks similar to mdx mouse muscles treated with corticosteroids -the current standard therapy for people with the disease. These medications slow the disease but have significant negative side effects.

Muscular dystrophy results from a deficiency in one protein, dystrophin. This protein, viewed as a pivotal component of a protein network, links a multitude of other proteins providing a physical framework for the cell. But what the study authors think curcumin is doing, has nothing to do with this protein assemblage.

Curcumin is well known to interrupt another protein, NF-kappa B, involved with regulating inflammation and stress. The authors hypothesize that the damaging affects of excessive NF-kappa B activity is reduced by curcumin.

Treating muscular dystrophy with curcumin is not a new idea. Another group, fed mice curcumin in hopes of lessening symptoms. But no effects were observed. The technique of injecting the compound seems to be the key probably because more curcumin reaches the blood stream and becomes available.

Is injecting curcumin a possible treatment for human patients? Could it replace current steroid treatments -or be used with them to treat the disease even more effectively. The doses of curcumin discussed are likely nontoxic.

Lead investigator of the study, Dr. Min-Sheng Zhu, Professor at Nanjing University in China, stated, “A daily injection is indeed difficult to be accepted for long-term therapy, but I think this difficulty will be overcome in the future if curcumin is effective in human as we expect. Actually, we have been making efforts to solve this problem. We don’t know whether curcumin can be used with corticosteroid treatment. Considering the side-effects, I think it should be OK.”

But what do practicing clinicians think about this savory idea of spicing up muscles? I attempted to find out by sending email to a reputable muscular dystrophy specialist. Unfortunately, I did not receive a response. So I'm calling on you, my reader to help out. If you work in the realm of clinical treatment, know someone that does or have personal experience on the topic, the readers here and I would love to learn more.

The image above, taken from Figure 2 of Pan et al. shows normal mouse muscle (C57BL/10), control mdx mouse muscle, and mdx muscle treated with curcumin.

Pan, Y., Chen, C., Shen, Y., Zhu, CH., Wang, G., Wang, XC., Chen, HQ., Zhu, MS. (2008). Curcumin Alleviates Dystrophic Muscle Pathology in mdx Mice. Molecules and Cells, 25(4)

Hormone Junkie: Treatment for Multiple Sclerosis

The MS solution, a book written by Kathryn R. Simpson, tells the gripping story about the author's own experience with multiple sclerosis (MS) and how she renders herself symptom free. Using hers and other case studies she illustrates the point: replacing hormones treats the disease. Written for people with MS, it guides the patient through the medical realm of neuroendocrinology.

I have read about studies -clinical trials even- that use estrogen or testosterone to treat multiple sclerosis and only wonder, why, if it works so well, it's not used more. Why aren't neurologists pouncing on this technique? She writes to this in the final words:

I will be the first to admit that this is a cutting-edge medical approach to MS; there aren't many doctors who specialize in treating hormone deficiencies, let alone have experience with using them in treating MS. You may be lucky and have an open-minded neurologist who will work with you on testing your endocrine system to see if this is a potential solution for your symptoms, but truthfully, I have found that this may not be the best medical specialty to work with in this approach. It's so far removed from a neurologist's medical training and clinical practice that it may be easier to find a forward-looking general practitioner or endocrinologist who has some exposure to hormone testing and treatment.

Simpson relates the disease to hormone equilibrium discussing the roles of estrogen, testosterone, thyroid hormones and others. Through her story, she touches on each and every hormone, how they decline with age, and how this relates to disease. By carefully replacing her hormones (lots of them -maybe, most of them), she describes how her symptoms vanish.

The book is inspiring and easy to navigate, while based in real science and believable anecdote. My only criticism is the cutting-edge research is cut a little short. Clinical studies were left without mention. This does not at all diminish the potential the “solution”. In fact, should I develop the devastating symptoms that accompany such a neurological disease, I'd soon be a hormone junkie.

Beer Goggles and Strobing Lights: What Your Brain Thinks About Alcohol

Neuroscientists have discovered -from the brain's perspective- what social drinkers already know: alcohol feels good, is relaxing, and you know how tipsy you are.

Imaging activity in the brain while administering alcohol intravenously, researchers from Brown University and the National Institute on Alcohol Abuse and Alcoholism, investigated how alcohol relates to emotion. Subjects underwent functional magnetic resonance imaging (fMRI) while receiving alcohol or saline. During the procedure, they were shown pictures of neutral or threatening faces -a technique known to elicit a fear response.

As expected, subjects given saline showed activity in the brain corresponding to regions relating to fear (including the amygdala) when viewing the threatening photos. The alcohol recipients, however, did not display this response. And, under the neutral image condition, they showed increased activity in areas of the brain having to do with pleasure and reward (ventral striatum).

A striking proportion of the reward regions showed activity in the alcohol condition. That the brain is saying “cheers, this drink feels good,” has implications to the study of alcohol in relation to addiction and alcoholism treatment.

The fact that alcohol abolished the fear response, readily triggered in control subjects, is intriguing. The authors speculate that because alcohol also affected the visual and limbic brain areas, an inebriated individual might see or interpret faces differently than their sober counterparts do. Perhaps this could explain the beer goggle phenomenon. Additionally, the data relating to the amygdala itself suggests it may play a role in misconstruing the presented expressions resulting in difficulty discerning friend from foe.

An unexpected finding relates to how individuals perceive the extent of their inebriation. Perception of one's intoxication did not reflect blood alcohol levels. However, people could seemingly sense how active their ventral striatum was. The more activity in the reward center -swayed by circumstance- the more a subject reported drunkenness. So, while you might not be able to tell what your blood alcohol level is, you can tell how tipsy you are. Perhaps this could explain why the strobing lights of a night club are part of the party while the flashing lights of a patrol car are sobering.

The above image, taken from Gilman et al. (Fig. 1A), shows activity in the ventral striatum in the alcohol condition.


Gilman, J.M., Ramchandani, V.A., Davis, M.B., Bjork, J.M., Hommer, D.W. (2008). Why We Like to Drink: A Functional Magnetic Resonance Imaging Study of the Rewarding and Anxiolytic Effects of Alcohol. Journal of Neuroscience, 28(18), 4583-4591. DOI: 10.1523/JNEUROSCI.0086-08.2008