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Nov 30

The court jester’s (harlequin) job was to entertain the court with his/her music and juggling abilities. The court members laughed at the jester (maybe not with him), but possibly the jester had the last laugh since his various entertaining endeavors possibly promoted in his brain greater plasticity and health.

All this week I will discuss several articles that examine the effects that musical playing and juggling has on the brain. Additionally, since it is the start of the festive season that usually includes more music being played at home and in the malls I think the timing is appropriate (not to mention a large number of mp3 players and music will be purchased during the festive season).

Now I am neither musical or can juggle (but maybe I should learn) so bear with my lack of expertise in this field (but hopefully I can explain the scientific findings) – and don’t ask me to sing silent night to you unless you are into auditory suffering – but I think this week’s series of blog pieces will be both entertaining and informative.

Many famous painters and writers used the court jester (or harlequin) in their works, including Picasso and Shakespeare. Maybe the below painting by Picasso will promote a little plasticity to start you out this Sunday. The first piece of the week will appear Monday morning.

Dora Maar au Chat, 1941

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Nov 27
DNA damage, due to environmental factors and n...

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A new paper just out in Cell by the Sinclair group gives us some intriguing but sobering information about aging and genomic integrity.

The new twist to the ever evolving story is the Sirt1 protein might have at least two primary roles in the cell. The first role is to locate itself on DNA to inhibit these particular genes that it is situated on for they are not needed by this particular cell at this time. The second role though is to help repair DNA damage caused by such things as oxidative stress. Sirt1 leaves its original location in which it was suppressing specific genes to where the DNA is damaged and hence they are no longer doing their gene suppressing job.

As the short review article in Science pointed out – this is a catch-22 situation (the catch-22 of aging).

In the paper when they induced oxidative stress there was a Sirt1 dependent dsregulation of gene expression – which resembles that of an aging mouse brain (see below). With the oxidative stress Sirt1 was relocated (from its original sites of action) to the DNA double-strand breaks. If Sirt1 was reduced there was less efficient repair of these DNA breaks. Interestingly, overexpression of Sirt1 repressed 85%  of the formerly deregulated gene expression.

Next the researchers irradiated mice to induce cancer in a specific mouse strain prone to developing cancer (p53 +/-) and found the Sirt1 activator resveratrol if fed 3 weeks prior to the irraditation increased survival by 24%. Since resveratrol might not be just working through increased Sirt1 activity they used a transgenic aniamal that allowed temporal and tissue specific overexpression of Sirt1. A 2-4 fold increase of Sirt1 expression in bone marrow lymphocyte progenitors and mature B and T cells was induced 2 weeks prior to exposure of the mice to irradiation. Survival in the Sirt1 induced animals increased by 46%. Finally, they found that overexpression of Sirt1 in the mouse brain could repress the age related deregulation of certain genes.

I am only give you brief outline of the paper, I encourage you to read the full thing if you are a scientist for even if this is not your particular scientific interest it is thorough and involves many interesting techniques.

Take home messages:

Aging could be a catch-22 situation – Sirt1 steadfastly performs its normal function of suppressing inappropriate gene expression but when there is DNA damage it abandons the castle to fight off genomic instability – but at the cost of deregulation back on the home front. However, overexpression of Sirt1 (via resveratrol and/or more direct genetic manipulations) can at least partially rescue the adverse affects of the accelerated irradiation induced ‘aging’ (genomic instability – increased cancer). Think of it as if you have enough soldiers you can both defend the home castle and fight wars in far off lands (though I am not a big fan of war like analogies).

Remember dietary restriction (in the form of calorie restriction or every-other-day fasting) has been reported to increase Sirt1 expression and dramatically decrease the incidences of cancer (tested numerous ways including radiation induced cancer), and increase genomic stability. Sounds famliar doesn’t it.

Nov 26

Here is a follow-up to my Monday post on the quick rebound from an exercise layoff in the important brain health protein brain-derived neurotrophic factor (BDNF).

A new paper published in the Journal of Applied Physiology examined running, BDNF, trkB, neurogenesis (new neurons), and neurite outgrowth (branching of the new neurons) in middle age rodents.

Both BDNF and its receptor (trkB) declines in the brain as animals age and this reduction is correlated with the reduction of new neurons (neurogenesis) in the adult brain. There is a precarious drop from age 3 month to 13 months old (middle age) where things start looking like a flat line out to 24 months. For example 13 month old animals only have 3-5% as many new immature neurons (neurogenesis) in the hippocampus (important for memory and possibly general mood) as compared to 3 month old animals (which would represent young teenagers in humans). The question the researchers asked was can 5 weeks of treadmill running reverse this downward trend in middle age animals?

The actual exercise paradigm start out with 20 minutes the first day (at 10 m/min) then 10 minutes of duration added every day until they reach 60 minutes of running per day (they are running at around 70% of their V02 max). This is interesting as most rodent running neurogenesis studies put in a running wheel and the animals run a great deal (up to 10 km per day – and think of how small they are) where in this study they restricted running to a level that is more reasonable for humans – one hour per day.

5 weeks of treadmill running increased the levels of both BDNF and trkB. What is interesting is that this short exercise period produced levels of these two proteins in 13.5 month old animals (started running at 12 months of age after a one week habituation to the treadmill – they usually live 24-30 months – hence middle age animals) to levels above sedentary younger animals (9.5 month old).

The number of neural stem cells (NSC), but also the number of immature and more mature neurons were increased with running in 13.5 month old animals – to the point it was slightly above the 9.5 month old sedentary animals (but still quite a bit below running 9.5 month old animals) . Additionally, the dendritic branch pattern of these new neurons were increased to a more mature neuronal state (their measurement for more mature neurons).

Take home message:

Most of you reading this are not young teenagers (far as I know) so your rate of neurogenesis is drastically decreased and hence you should be out there exercising. According to this paper an hour a day at roughly 70% of your Vo2 max which equates to approximately 80 % of your max heart rate.

Nov 25

Most scientist that are attending a conference are in one way or another funded by the tax payers so I think we have an obligation to make the most of any meeting we attend.

So what are some of the criteria that should be met? (in my opinion)

1 – Try to travel there at an economical rate: e.g. flying economy – not business or executive. And is there really a need for so many scientists to attend 10 to 20 conferences a year – how much new information can there be in a chosen scientific field (that couldn’t be read about in journals) if you are attending one or two conferences a month - talk about a large carbon footprint.

2 – Attend the conference (you would be surprised sometimes what percentage of conference sessions are attended by scientists). One example was for the opening of the most recent conference I attended (a very large one) I could not believe how many people were heading away from the conference center (they had picked up their badges etc) to tour the city instead of attending the conference.

3 – Try to take in the appropriate scientific information that is available at the conference (as an example there were over 15,000 posters and talks at the recent conference I attended), so there was more than enough for everybody special fancies and interests.

4 – Present your recent scientific work to the scientific community honestly and frankly – warts and all (don’t just try to present a tidied up story).

I am sure I and others could add more, but I think this is a minimal level.

Additionally, for my personal check list my main goal at a meeting is to acquire enough scientific information that I am able to generate a new idea/scientific experiment of worthwhile quality (or at least it at least seems new to me – though others might have thought of it before).

In my most recent meeting despite having picked out and read over 500 abstracts (most of them several times to try to find a common theme among the divergent stories) and closely examining approximately 150 posters/talks at the meeting I failed to come up with a worthwhile new idea (sure I came up with plenty of ideas but not that I would judge as good enough to pass my criteria). I personally failed the taxpayers in my mind. I have no excuse. This led me to feeling pretty depressed at the end of the conference when I realized my failure (this is the first conference this has happened to me).

Scientists try to be responsible with your use of tax payers money at meetings, and all of your other scientific endeavors

Nov 24

I have previously written a few times about how quickly deconditioning of aerobic fitness occurs after an exercise layoff (see here and here), but what about brain health?

I have a perfect reason for writing this new piece because with my recent travel schedule (multiple cities, multiple meetings, etc), busy conferences, and maybe an extra busy social calendar has combined to halt my running over the last two weeks (this is really not a good excuse for I saw many neuroscientists up in the early morning running before the conference started as I walked to the conference centre). The question then is how much aerobic and brain deconditioning occurs?

Aerobic fitness declines after a layoff (no aerobic exercise)

Alan Couzens writes in his blog piece – with supporting data from scientific papers – it takes considerable time to recover that lost fitness after even a short lay off (not to be confused with tapering) – and hence it is best to stay consistent. A one to three week layoff results in 25-30% drop in actual performance. Even one week of no exercise results in a 50% drop in mitochondria (your energy producing engines)  and it can take 4 additional weeks of training to bring those mitochondrial numbers back up to where they were before the layoff (and hence performance).

Brain fitness after a layoff (no aerobic exercise)

What about the effects on brain health after a physical exercise layoff? There is not a lot of research on this subject but several papers are quite fascinating.

Many papers have found that with running the amount of brain-derived neurotrophic factor (BDNF) is increased in several brain regions (the hippocampus is usually studied) and reported to increase neurogenesis (a good thing) and be involved in reducing symptoms of depression. In general BDNF is very good for your brain health (I should write a blog piece on this important brain health protein).

TrkB signaling

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But what happens when you stop running? Widenfalk et al., 1999 reported that when you stop running BDNF drops – with a trough occurring 5 days after stopping running (and still lower at 10 days). And even 30 days after stopping the BDNF levels in the CA3 region of the hippocampus region while not statistically lower (at a 0.05 level) appears to remain lower than the levels prior to stopping running. The good news though is that even at the lowest levels BDNF is not lower than prior to starting running. Therefore, even after 30 days of no running the prior running animals BDNF levels remained higher than before they started running (they also saw the same overall results for the receptor for BDNF which is called TrkB or TK+ in the image).

Additionally, exercise also increased neurogenesis in a recent human study, which is presumed to be mainly due to increase of BDNF (Pereira et. al., 2007) (in reality they only used a correlate measurement of neurogenesis which the validated in a mouse model – but it is the best they can  do for a human study).

In a more recent paper (Radak et al., 2006) using swimming (5 times/week, 2 hr/day, for 8 weeks) and found the typical increase of BDNF with exercise. However, after 6 weeks of detraining BDNF levels (measured by a more sensitive assay than the above paper – ELISA) on the whole brain were below the pre-exercise levels. Another brain trophic factor (nerve growth factor – NGF) also fell after detraining to levels below the baseline pre-exercise period. The memory improvement effect which occurred with exercise was also lost with the cessation of training.

Okay, this doesn’t sound so good – BDNF dropping to levels lower than before you started running. This could be related to the ‘depressed’ feeling people experience when they stop running (be it due to an injury or other situations) – though many other molecules including possibly the immune system may be involved.

However, there is also some good news.

Berchtold et. al., 2005 found a number of interesting results. In their running paradigm it took 14 days of daily running for BDNF to increase above the pre-exercise levels. Additionally, they found that you don’t have to run every day to keep BDNF levels up. While running 6-7 days a week might be optimal at a aerobic fitness level, according to animal studies running every 2nd day was just effective as running every day to increase brain BDNF levels. It took slightly longer for BDNF levels to increase above pre-exercise levels when running every 2nd day (21 days for every 2nd day vs 14 days for daily running).

In this paper it took between 7 and 14 days of non-running for BDNF levels to drop to pre-exercise levels (they didn’t look at longer time periods to see if they would drop below pre-exercise baselines as the above study).

But the most interesting part of this paper is when they re-introduced exercise to the animals after a two week layoff (just like my current condition). It only took 2 days of running to increase BDNF levels – where normally it took 14-21 days. There was a slightly better effect if the animals where doing daily exercise compared to alternate days. But the real message here is that there appears to be a ‘molecular memory’ of your previous running – a conditioning of the system – so when exercise is re-introduced the positive effects occur far earlier.

Take home messages:

Yes, try to be as consistent as possible with your exercise program. A two week total lay-off will result in considerable aerobic fitness loss that requires possibly 4 weeks to recover back to your previous levels. However, in regards to BDNF (which may help your mood, memory, and brain plasticity) as little as two days of exercise will result in a re-introduction of increased BDNF levels.

With that said I managed my second run since getting back home – hopefully the BDNF is kicking in – we all need our daily dose of BDNF.

So if you have an extended layoff it is not all bad – get out there and get all the brain health benefits of exercise and it will only take a couple day of exercise to get back up to your old levels, yippee!

Nov 21

A large part of the neuroeconomic research field is the study of human irrationality. It can be argued that our propensity for irrationality leads to many of the problems of our modern society (but I won’t go into the details at this present time). Now I will present I personal example for your amusement.

At the recent large neuroscience conference (SFN: Nov 15-19, 2008) I was offered a new post-doc position with a 50% pay increase! The new post-doc offered a great opportunity to further examine novel neuroprotective treatments in a great and clinically relevant model, that has near unlimited opportunities for me.

I turned down the job – which is in itself highly irrational – for the obvious difference in pay, but also my current position is only funded for the next 6 months – not to mention the additional factor of the current worldwide economic conditions. What I did next though really makes me question this whole rational human thing (at least at a personal level). I then turned and made a counter offer to the principal investigator I would work for him free on part of the problem.

Now that is some negotiating strategy, going from a 50% pay increase to offering to work free for him.

How irrational, not to mention stupid is that? This is all despite my additional scientific interest of studying human irrationality (so in theory I am not ignorant of this human pension for irrationality). Maybe I should have my head scanned - I think I might know what it will find :)

Additionally, there are no rational reasons particularly keeping me at my current location and post-doc position.

So what I am suggesting is in your own day to day choices maybe step back once in awhile to check how rationale some of your choices are (hopefully they won’t be as irrational as my one personal example I am sharing).

Nov 13
La Bohémienne endormie  (The Sleeping Gypsy – ...

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Brain stimulation for a healthy brain can come in many forms – for the past couple days it has been touring NY city and visiting museums. I visited the MoMA (The Museum of Modern Art) today as part of my final art plunge brain stimulation activity in NY city.

What struck me was one of the audios in which a 19th century artist said something to the effect of: the 19th century artist sees a thousand times more in a lifetime than an artist from the 18th century and that obviously this difference will require new art forms to convey the new reality.

I assume he meant that most 18th century artist didn’t travel much, but also didn’t live in such big cities with a high density of people (therefore see less life/lives in a given day) and hence overall sees less ‘new things’ in a lifetime. This notion of taking in more information (seeing) than the previous generation somewhat struck me, but also made me jump to the 21st century.

Think of what the average 21st century kid will see in their lifetime. Not only traveling a great deal and many living in gargantuan cities, but the big difference is the TV/movies (traditional media) and the internet. Think of the hours of video information that are taken in over a lifetime (even a year) and the endless number of web pages. If the artist thought there was a big change from the 18th to 19th century – well then I would really expect a new art form for the 21st century. Of course the question is in what form it will take? I will suggest that it, being the product of the information age, will involve petabytes of information. The question is how to present this massive load of info. You cannot use a traditional canvas (a human cannot paint that high of density), might the art actually take the form of the net ? Is the new art form just plain and simple the net?

Will an artist of the 21st century by linking various sites (both personally made and other sites) to form an ‘image’, a feeling, an experience, a story? In reality of course this is being done today (and done in the past). Will there be new and better ways to perform this? Do we call this art today, will we call it art in a hundred years, will some form of this new art hang in art galleries of the future – or will we all be using the net to view the new art?

Okay – enough of my art musings, off to society for neuroscience annual meeting tomorrow where 30,000+ neuroscientist descend to view all the latest and greatest neuroscience.

What did you do today to stimulate your brain?

Nov 13
Colour Doppler of Common Carotid Artery

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How healthy are your arteries that supply the blood to your brain (carotid arteries)? Your brain health is influenced by getting an adequate blood supply. What do you think happens to your brain health if it is not getting sufficient blood supply due to blocked unhealthy arteries?

A frightening new study (abstract published at the American Heart Association meeting) indicates that for at risk children (obese or high cholesterol with an average age around 14 years) their vascular age was that of a 45 year old. Scary !

Using ultrasound imaging of the neck arteries (measuring the thickness of the inner walls of the carotid (neck) arteries – these are the ones supplying blood to the brain) of these children they could compare them to various age ranges to get a vascular age of these group of kids.

On average these kids had a cholesterol level of 223.4 mg/dL, LDL cholesterol of 149.8 mg/dL, triglyceride levels of 151.9 mg/dL.

The triglyceride levels of over 100 mg/dL was the best predictor of advanced vascular aging among the lipid risk factors. And those kids that were obese and triglycerides above 100 mg/dL were even worse off.

Do you know your cholesterol and triglyceride levels and what the norms are? If you don’t maybe you should.

What best correlated to the bad carotid artery inner wall thickness was the simple body mass index (BMI) and higher systolic blood pressure. Two fairly easy measurements for all of us to obtain. For a simple BMI calculator go here. Overweight is anything above 25, and obese is anything above 30. Go to your doctors or a drug store and get your blood pressure measurements.

You want a healthy cardiovascular system if you want a healthy and functioning brain. Everything is connected.

Back to the 14 year kids with arteries of a 45 year old. This is not a good picture, not a good future. Thirty years added to their age which would suggest they are more likely to die at 45 instead of 75. And I would guess that this increased age of arteries keep on getting worse with a continuation of their current lifestyle. Instead of their arteries 30 years older than their real age, maybe it stretches out to 40 or 45. A truly scary scenario. And think of the current epidemic of obesity in children, what does this hold for the future of this generation? Will for the first time in current developed nations we have a decrease in lifespan – or we will spend billions upon billions to use advanced modern medicine to keep them alive, and what will this cost society not only at a financial level but at a functional level?

Do what ever you can to have a healthy cardiovascular system; exercise and eat healthy – and try to do this everyday.

Nov 12

In my continued search of further brain stimulation on my current trip I visited some art galleries in Chelsea (Chelsea art galleries) (in NY city). Supposedly over 300 galleries between 10th and 11th avenues and 19th and 29th streets. I didn’t see anywhere close to 300 but I did randomly explore quite a few.

Yesterday, I posted about my visit to the metropolitan museum of art – that was good in many ways but a bit disappointing (with the exception of the ancient Egyptian carved walls). But today the art galleries were highly inspirational and stimulating. This might be due to the art I saw today was new and live – not the art of history. I did not know the name of the artists so I had no preconception, I simply walked in and let my eyes and mind explore. The galleries were vibrant with life – fresh paint, fresh thoughts. Now not all the art was personally stimulating to me and I wonder which of the multitudes of artist will ever ‘make it’? Though that mabye doesn’t matter, they are out there trying, living their dream.

One particular gallery really caught my interest. The art was in what I assume the edgy comic book genre. You could see, feel the inspiration, the drive, the flurry of thoughts and these simple but detailed and interesting mostly black and white panes. Very cool and interesting. I took some photographs which included the name of the artist so I can investigate later. Additionally, there was a gallery with some big carved granite installation that were impressive. I am sure there is plenty more to explore – if I can find the time tomorrow in my last day in NY city.

Art is alive in well in NY city.

Go out and explore art in your area – be it a singer playing a tune at a nearby bar, a poet slamming in a cafe, an artist’s painting hanging in a local gallery, or a novelist in a nearby coffee shop (though this one is difficult to really enjoy :) ) – stimulate your brain.

Nov 11
Metropolitan Museum of Art

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As part of mind stimulating trip I have the opportunity to visit some museums. I am lucky enough to be in NY city and visited the Metropolitan museum of art – among the greatest in the world.

I strolled through the long and winding rooms and wondered would I think these are great painting if somebody hadn’t told me? Or at least that these seven (pick any famous seven) painters are clearly above the other painters who’s works aren’t hung on these prestigious walls (and are largely or completely forgotten) for millions to see each year? Already the museum had at least got me thinking – proposing thought experiments.

I remember several years ago, after having spent 3 weeks in Europe and visiting various museums, when I walked into a Washington DC museum and as I wandered around I saw a painting in the distance and I said to myself – ‘A Degas’ even though I didn’t recognize this specific painting. When I wandered up to the description sure enough in was a Degas. I was feeling pretty proud for an artless scientist.

Therefore, today I was somewhat mystified when at the museums several times I was wrong with my guess of the artist. I thought I recognized the Pointillism style of X and it would turn out to be Y (pointillism is just one example of impressionism and post-impressionism). Then I realized as I looked closer (without remembering the names), at least to an untrained and schooled eye, that it seemed liked there were little groups that all pretty well used what I use to think of as a distinct style. I am sure somebody with a little bit more art knowledge would surely set me straight – but still there are some similarity in some of the techniques used by the various members (if they were not copying there were ‘heavily influenced’ – not to say the same thing doesn’t happen in writing and/or science).

This throw me for a few minutes because my simplistic understanding of the late 19th century paintings were the exploration of new ways to look and interpret the world. They we could view the world through individual specific perceptions – but if they were just copying each other – . Early in the day I saw the rich colours and brilliant lighting techniques of the Renaissance and Baroque painters (and throw in Romanticism). Yes, they were beautiful but how many different ways can you depict reality in a straightforward manner (even with very dramatic lighting)? I had heard of several books that highlighted the changes in science and physics that fostered the new art (or vice versa – not sure about the chicken or egg argument in this case). My artless trained conclusion was how many ways can you depict a new reality – hence they soon started copying each other. And like the Renaissance painting style this new exciting departure from normal reality also gave way to the even newer and bolder attempts of modern art (modernism, post-modernism). Okay, enough of my overly simplistic art history lesson (which is I am sure somewhat misguided).

Sadly, I wasn’t inspired today at the museum – maybe because I have seen enough art (in the form of history) as now I only see slight derivations of things I have seen previously from the various museums I have visited around the world. (I also found myself in the middle of my visit to this museum pulling out my laptop and doing a little science as I glanced up at a Degas’ between my work on the computer – actually I guess I am pretty luck to be doing work in such beautiful surroundings).

But I do draw myself near to a Van Gogh painting – looking closely at the splotched on paint – layered thick and richly. I ponder of how his work, his inspiration is congealed in this one time piece of work that can not be copied – that globe of paint smeared with that specific color, that specific slash, that specific motion. His art does seem particularly full of energy – if that is possible.

What struck me the most today was when I visited the ancient Egyptian art section and they had stones wall carvings with hieroglyphics writing. I was not really sure if these were originals (but I assumed so), or copies. But I thought of the person who 5,000 or so years ago worked away to make this wall art. Was he a free person or a slave? Did he enjoy his work, or did they have any choice? But still the work has lasted – not in its original location half way around the world – but sits in a Central park museum on some of the richest land in the world. This art piece is viewed by millions and millions and over years and years. I wonder what is the artist’s story? This made my neurons and brain sing.

Stimulate your brain – take in some art, be it in a book, on the web, or stop by a local gallery in your area (you don’t have to go to some world class museum to view art). Sure you might have some disagreements with what the experts think. You might even have thoughts of your own – and there can not be too many things more stimulating for your brain than some honest to gosh thoughts. Maybe you will even be stimulated to produce some of your own art.

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