Concussion repercussions

I went to a Montreal Canadiens game last week, with the Bruins as the visiting team. The atmosphere in the Bell Center was festive, as the Habs went up 4-0 in the first two periods. The mood shifted drastically, however, as a Canadiens forward was checked into the stanchion between the benches and fell to the ice, unconscious.

The now-infamous hit by Zdeno Chara on Max Pacioretty resulted in a serious concussion, as well as a fractured C4 vertebra. Amid the controversy regarding the hit and whether further disciplinary action should be brought against Chara, the incident brings the seriousness of concussion injuries back into the public eye.

A concussion is a form of traumatic brain injury, in which a sudden impact causes the brain to compress against the inside of the skull, resulting in a temporary loss of brain function. The majority of concussions do not result in loss of consciousness. Roughly 1% percent of the population will suffer from a concussion at some point, although this statistic is likely an underrepresentation of the true prevalence. We used to view concussions as relatively minor events, but some disturbing recent studies have shown that they can have serious consequences.

Common side effects of a concussion are headache, nausea, loss of motor coordination, and sensory dysfunction. These usually dissipate without requiring treatment acutely after the injury. However, with post-concussion syndrome, symptoms may not disappear for months or years, or even at all, and there is currently no treatment except rest.

We are also learning a rapidly increasing amount about the effects of concussion on emotional and cognitive function. Recent studies in National Football League players have shown an association between concussion and depression, as well as memory deficits and general cognitive impairment. Tragically, traumatic sports injuries have even been linked with suicide. These effects have been attributed to chronic traumatic encephalopathy, a degenerative condition in which multiple head injuries lead to aggregate damage to the brain; boxers that are termed ‘punchy’ suffer from one form of CTE.

Pacioretty will hopefully recover from his injuries avoiding these particular issues, although his future career is in doubt. However, the primary issue is that millions of young athletes engage in contact sports on a regular basis, putting developing brains at risk for serious neuropsychological consequences. It is imperative that future research determines how best to mitigate the risk of concussion-related injuries in these vulnerable individuals.

****

On a lighter note, this week is Brain Awareness Week, so make sure to attend some of the great events and get involved!


- Ian Mahar
[Adapted from a post originally posted here.]

Human Libido = Mouse Libido?

(crossposted from The Naive Observer)

No! Right? Maybe some sociobiologists would argue that they obey the same basic rules, but no, not the same. Not so fast though – anyone who has had to defend their mouse research against doubts about its relevance will tell you (a little too earnestly) that there is around 90% similarity between the mouse and human genomes. So in all your faces, non-mouse geneticists.

Many of us use mice and rats as model organisms to study things from a genetic point of view with reasonable hope that info gleaned from rodents will inform our knowledge of human biology and direct “less invasive” research on humans. But there’s no denying that humans and rodents are very different. So where do we draw the line when inferring from rodent studies? This problem is especially relevant in neuroscience, where we are caught trying to bridge the gap between the physical, cellular, genetically influenced brain and the less tangible, socially conditioned mind. What better way to give air to this issue than by juxtaposing the genetics and neural correlates of mouse and human libido?

Last year I reviewed a study that discovered that male mice release a small aphrodesiac molecule (ie pheromone) in their tears. This small molecule, called ESP1, makes female mice more receptive to males’ sexual advances. In other words, female mice are turned on by the smell of tears in their man’s eyes.

So, er… “a friend of a friend” read that study, was thoroughly convinced and, armed with the knowledge that mice and humans are genetically quite similar, took his tears to the bedroom, hoping to turn over a new leaf. Unfortunately he neglected to look at what seemed to be a follow up study in humans in the new year. Turns out female human tears contain a substance that does the exact opposite, decreasing male arousal when the men sniffed paper soaked in tears collected from women. (Is sniffing tears not creepy? What ethics committee approved that?) True enough, the authors only looked at female tears, so maybe there is a human analogue of the male mouse tear aphrodisiac. So, in the interest of being fully honest, guys, if you want to run the risk, you can still have a go at crying. However, it turns out that the friend of a friend shouldn’t have risked it; last I heard he’s lonely and writing a blog or something.

The point is that humans and mice are similar in some instances, and opposites in others. So there is no point. Rest assured that rodents will continue to provide a popular and invaluable model organism well into the future. That means when you see something in the paper to the tune of “Now-Famous Scientists Show Such and Such Will Make Someone Special Horny” or not, before hitting the streets in search of Such and Such, figure out what species the research was done on and make your own tentative judgment.

Reference

Gelstein S, Yeshurun Y, Rozenkrantz L, Shushan S, Frumin I, et al. 2011. Human Tears Contain a Chemosignal. Science 331: 226-30

Synesthesia

Does your best friend's name taste like macaroni and cheese? Does your favourite song look like a blue bolt of lightning? Is four red?  If so, you are most likely a synesthete - a person who experiences the rare neurological condition synesthesia. Synesthesia occurs when a stimulus induces not only the expected percept (perceived representation) but also an involuntary, automatically evoked percept, sometimes in another sensory modality. For example, the most common form of synesthesia is grapheme-colour - where seeing, hearing or thinking of a letter or digit evokes a colour. These associations are highly consistent (e.g. the letter A, will always evoke the colour green), and are present from childhood. For some synesthetes, the concurrent percept is projected into a specific location in space (i.e., right onto the grapheme) - these are called projectors. Associators, on the other hand, see the elicited percepts "in the mind's eye".

                It is only in the past few decades that research involving synesthesia has flourished. Historically, the condition was regarded with much skepticism. At worst, synesthetes were condemned as mentally ill, and confined to asylums , at best they were considered to be overly imaginative, or liberally metaphorical. In the last two decades innovative, psychometric methods have also been used to empirically demonstrate and stud the existence of synesthesia. Tons of behavioral findings have demonstrated that synesthetic percepts behave like typical sensory percepts in attentional tasks, which established their perceptual reality.

                In recent years, the focus has now shifted towards forming an explanatory framework for interpreting the various empirical findings. One difficulty in putting forward a complete framework is that there is a lack of knowledge concerning what is is about a synesthetes brain that is different from someone without synesthesia. For many years, synesthesia has been vaguely attributed to "crossed wires" in the brain. Despite sophisticated brain imaging methods (like fMRI and PET scannin), and substantial progress in neuroanatomy, the underlying mechanisms of synesthesia remain elusive. Several competing theories have emerged, with the main disagreement being whether the pathways implicated in synesthesia are unique to those with the disorder - indicating the presence of a structural brain difference - or if they are present in the normal population - indicating the presence of a functional brain difference.  So, the question comes down to: extra wires or altered functioning?

If you're interested, check back for parts two and three, where I'll review some evidence for each of the sides of the debate!

For lots more information on synesthesia, including personal anecdotes, check out: http://www.mixsig.net/.

Hilary D. Duncan

Concordia University

"Parkinson's Disease: Working Towards a Cure" Part 3 -- Towards a Cure

This is the third post from a three part series written by Andrew Greene, a graduate student at McGill University studying Parkinson's Disease.

Rather than giving a broad, but ultimately superficial overview of modern research in the field of Parkinson's disease I'll try to delve more deeply into one particular line of research that I believe holds great promise. It's important to keep in mind, however, that there are many other exciting avenues presently under investigation around the world that could prove more effective. It's also important to remember that much of the research I'll be discussing is still very new, and the interpretations that myself and others are drawing from it have not yet been firmly established as correct.
     Let's begin by taking a step back and recalling that the movement-related difficulties that afflict those suffering from Parkinson's are largely due to the death of a subset of brain cells (neurons) known as the dopaminergic neurons of the substantia nigra pars compacta. The ultimate goal therefore becomes finding a way to stop these neurons from dying, but to do that we first need to understand why they die. This has proven to be an incredibly difficult question to tackle, and the laboratory in which I'm conducting my research is just one of many around the world that are dedicated to it. 
     Particularly puzzling is why these neurons, which I'll call SNc DA neurons for short, succumb when other groups of neurons remain healthy. The obvious answer is that they have intrinsic properties that make them different from other neurons, and this has led many labs to characterize SNc DA neurons in detail to try to find what makes them so special. James Surmeier's lab in Chicago has identified some particularly interesting attributes, which may very well contribute to the SNc DA neurons' selective vulnerability. Foremost among these is the heavy reliance of SNc DA neurons on an unusual type of calcium conductor called an L-type calcium channel. SNc DA neurons take in large amounts of calcium through these channels at regular intervals as part of their normal signaling processes. The problem is that despite calcium's important roles in bone formation and cell signaling it's actually quite toxic when too much of it accumulates within a cell like an SNc DA neuron (don't worry about drinking too much milk though, any excess calcium that you consume is stored in your bones, which makes them stronger and keeps the calcium out of sensitive areas; SNc DA neurons don’t take up so much calcium because the person they’re a part of is imbibing too much of the stuff, it’s simply a normal part of how they function). Because this calcium 'ingestion' is an ordinary part of an SNc DA neuron's second to second activity these neurons are equipped with miniature pumps that pump calcium out before it reaches toxic levels. However, these pumps require a massive amount of energy to power, and thus represent a heavy burden for the SNc DA neuron's metabolism. On top of this, SNc DA neurons each make approximately 370,000 output connections with other neurons, hundreds of times more than what most other neurons of the brain make. These output connections also require a massive amount of energy to maintain and operate, adding to the energetic burden imposed by the calcium pumps.
      How is all this energy produced? Cells have internal organs much the way people do, and the organs responsible for using the combination of oxygen and food to produce a cell's energy are called mitochondria. Each cell has many mitochondria that work collectively to meet the cell's energy needs. Because SNc DA neurons have such high energy requirements their mitochondria have to work double time. This is problematic because mitochondria produce toxic chemicals called reactive oxygen species as by-products of their effort to supply the cell with energy. The harder the mitochondria are working the more reactive oxygen species they produce, and these toxic chemicals can go on to damage various elements of the cell, including DNA and the mitochondria themselves. This damage accumulates in SNc DA neurons over a person's lifetime, and can ultimately lead to the neurons' death.
     If SNc DA neurons produce so many toxic molecules you may be wondering why they don't die off in all of us as we age. In fact they do, and what separates a healthy elderly person from someone with Parkinson's disease is how many have died. You can be pretty much symptom-free with up to 80% of your SNc DA neurons gone, but once you lose more than that you start to have serious problems.
    So why do some people lose almost all their SNc DA neurons and get diagnosed with Parkinson's disease while others reach ripe old ages without even getting close to the 80% threshold? The answer to that is almost certainly quite variable. In some cases it appears to be due to exposure to certain toxins that damage mitochondria and/or enhance the production of reactive oxygen species. In other cases the problem lies with inherited mutations that may increase reactive oxygen species production or affect a cell's ability to survive them. In most cases it's probably a little of each.
      Classic examples of the kinds of mutations that can lead to inherited Parkinson's disease are those found in two genes called Parkin and PINK1. The vast majority of genes, including Parkin and PINK1, are encoded in your genomic DNA, which is contained in almost every cell in your body. The DNA itself is essentially just a set of instructions, and generally doesn't take an active part in the functioning of a cell. The instructions encoded in each gene usually allow for the manufacturing of a particular protein, and these proteins are what perform most of a cell's functions. For example, it's now well established that mitochondria produce energy thanks in large part to a collection of proteins that lock together to form a molecular machine known as ATP synthase. ATP synthase acts much like a hydroelectric power plant, except that instead of using the energy from water flow it uses the energy from protons flowing through a small opening in a fatty membrane, which acts as a dam. The flow of protons quite literally spins a miniature turbine contained within ATP synthase, and the energy from the spinning of many of these turbines is used to power the cell.
      The proteins encoded by the Parkin and PINK1 genes are not directly involved in energy production, but what's becoming increasingly clear thanks to a landmark study by Richard Youle's lab in Washington is that they act together to perform a quality control function for mitochondria. As I mentioned earlier, one of the elements of a cell that can become damaged by reactive oxygen species is the mitochondria themselves. When mitochondria are damaged they often become less efficient and wind up producing more reactive oxygen species by-products, which can further damage themselves and the cell. The cell has mechanisms to repair mitochondria, but when mitochondria become so damaged that it's impossible to fix them they have to be eliminated to prevent them from running wild in their reactive oxygen species production. The Parkin and PINK1 proteins are responsible for identifying heavily damaged mitochondria and flagging them for a process called autophagy (literally meaning 'self-eating'), in which the cell destroys the defunct mitochondria and recycles their components.
     This is all well and good, except in people in whom Parkin or PINK1 are mutated. Mutations are errors in the DNA instructions, and they can result in the production of defective proteins. The mutated PINK1 and Parkin proteins that are found in Parkinson's patients are unable to perform the mitochondrial quality control survey undertaken by their healthy counterparts, which causes damaged mitochondria to accumulate. These damaged mitochondria function less efficiently and thus produce more reactive oxygen species by-products, putting more stress on cells. This is particularly detrimental for SNc DA neurons since, as discussed earlier, they are already heavily burdened in this department. Losing mitochondrial quality control processes probably explains at least part of why people with grave mutations in Parkin or PINK1 almost always get Parkinson's disease, usually at an abnormally young age.
    While the molecular and cell biology described so far is interesting in its own right, it also serves a critical role in designing treatments for Parkinson's disease. Since we are beginning to understand what might be killing SNc DA neurons we can identify ways to protect them. Anti-oxidants that soak up reactive oxygen species could be a good start, but there are others. For example, drugs that can enhance the mechanisms that eliminate defunct mitochondria may be able to reduce the production of reactive oxygen species in SNc DA neurons (and other cells) and thus slow the progression of the disease. Another promising therapeutic avenue is forcing SNc DA neurons to stop relying on the L-type calcium channels, thus reducing their energy requirements and corresponding production of reactive oxygen species. This has already been shown to work well in mouse models of Parkinson's disease, and will probably move into clinical trials in the near future.
    As I emphasized in the beginning, what I've described here is only a glimpse of some of the exciting discoveries that are being made in the field of Parkinson's research. There are now many competing theories to explain why SNc DA neurons die in Parkinson's disease, and time may prove one of them to be the most accurate. It seems more likely, however, that several of these theories are correct and there are a multitude of factors that contribute to SNc DA neuron death. The best treatment will thus probably not come in the form of a single drug, but rather a mix of molecules designed to protect SNc DA neurons from the various threats they face over the course of a person's lifetime.

Brains need love too

I recently saw the new ad campaign from the institute where I work (the Douglas Institute), ‘Brains need love too’. Seeing as the campaign touches on brain awareness-related topics (including the brain's involvement in psychiatric illness), as well as today being Valentine’s Day, I thought it deserved sharing. The video is extremely open-ended, with the actual message of the campaign open to the interpretation of the viewer, at least until they visit the campaign’s web site. Here are the initial interpretations I took away from it:

- Psychiatric conditions are neurobiologically based, as implied with the opening shots of brains labelled by psychiatric diagnosis. I’m assuming the reasoning behind this is that it has traditionally been believed that stigma against mental illness could be ameliorated in the general public if it was more widely known that mental illness is fundamentally due to the structure and function of the brain itself, as opposed to any personal weakness of afflicted persons themselves. Although it’s noble to attempt to combat stigma by replacing popular misconceptions with fact, however, recent studies showing that stigma against mental illness persists even in the face of improvement of the public’s understanding of the origins of mental illness sadly cast doubt on the effectiveness of this particular strategy.

- People are more than their labels, another anti-stigma message. Outside of its labelled container, the brain reveals it’s capable of experiencing life just like anyone else.

- Take care of your brain, not meant as an anti-stigma message but more of a suggestion that all of our brains, well, ‘need love too’. Speaking of which, Brain Awareness Week is coming up in the near future, so get involved if you need some spring brain-awareness-lovin’. I’m assuming the figurative message here is to be aware that your brain needs care, if not by skateboarding and psychedelic brain-tossing, then by nutrition, exercise, mental stimulation, paying attention to your mental and emotional functioning, and not-sniffing-glue-or-opening-doors-with-your-head-or-something. They’re pretty vague on this one.

Overall, it’s charming and cute, and I like the bold approach of using real (albeit calf) brains up-close and bloody to show that something that may seem disquieting to us (in this case, a bloody brain) is capable of experiencing cognition, emotions and the world around us. Similarly, although mental illness can be disquieting to those with a stigma against it, psychiatric patients are fully capable of these same experiences. Also, regarding the brain images, I feel obligated to point out that we’re talking about something we’ve all got, which is processing this sentence right now within your own head, and while you don’t necessarily have to realize how cool that is, you should at least try to get over your squeamishness over the look of your own brain. It is, after all, what ‘you’ really look like.

It’s a bit difficult to determine the overarching message of the campaign from the 62-second ad alone; it does seem to be necessary to go to the campaign website for clarification, where there’s a slightly vague description urging people to take care of their brains and, more usefully, a list of diverse resources for information on the brain as well as psychiatric disorders and treatment. However, despite this it’s a well-produced and genuinely endearing ad. So go love your brain.

-Ian Mahar

(Adapted from a post previously appearing here)

"Memory, Aging and Alzheimer's: When forgetting too much becomes a problem"

Although our brains produce new neurons throughout our lives, their overall number peaks in our early twenties and then gradually declines as we age. Certain forms of memory tend to get worse with age as a consequence. Episodic memory in particular is often weaker in the elderly, making it more difficult to remember where a car was parked, or what time a friend was supposed to arrive for dinner. The good news is that other types of memory such as semantic (remembering general facts and concepts) and procedural (remembering how to do something) memories remain robust in most people well into their later years.

Unfortunately this is not the case for people suffering from an increasingly well-known disorder called Alzheimer’s disease, which severely impairs normal memory. Alzheimer’s is the most common example of a spectrum of disorders known as neurodegenerative diseases, all of which cause neurons to die off more rapidly than they would with normal aging. The prevalence of Alzheimer’s increases dramatically with age, rising from just 3% in those aged 65-74 to almost 50% among those 85 years and older.

Currently available treatments tend to focus on minimizing the symptoms of Alzheimer’s by compensating for the loss of neurons. Some of these therapies can be helpful, but scientists have not yet found a ‘cure’ for Alzheimer’s, i.e. a treatment that would actually slow or halt the neuronal loss. This is because it’s still not entirely clear why neurons die in Alzheimer’s, although thousands of laboratories across the world are bringing us closer to the answer every day. We can hope that several of the many promising therapeutic avenues currently under investigation by scientists in Montreal and elsewhere will one day provide an effective means of combating the disease for both present and future generations. (Andrew Greene, McGill University)

All are welcome to join us on Wednesday, February 23rd, at 7:00 pm at La Sala Rossa (4848 boul. St-Laurent, Montreal, QC, H2T 1R6) for an evening of questions and answers, as we discuss memory and aging with world-class experts Andrea Leblanc, Ph.D., Serge Gauthier, M.D., F.R.C.P.C., and Judes Poirier, Ph.D., C.Q. Refreshments will be provided. This is a free event! We hope to see you there!

for more information: http://sfn-montreal.ca/baw/cafe/

http://www.facebook.com/#!/event.php?eid=183243215043955

hosted by BAW Montreal as part of our 2011 Brain Awareness Week public events. 

Thank you to our sponsors .

*** Our popular Science Cafés offer the public the opportunity to meet and discuss various topics in Neuroscience in an informal setting. These Cafés feature a Question & Answer with three to four guest panelists who are experts in their fields, snacks and entertainment. Our Cafés are always free thanks to our sponsors. ***

Monogamous cheaters

In my previous post I wrote about vasopressin and oxytocin, so-called “love molecules” that promote attachment and pair-bonding in voles and humans. These molecules act on receptors found in the dopamine-reward system to enhance the dopamine “pleasure” response thereby re-enforcing monogamous activities. However, socially monogamous voles, like humans, are prone to “mistakes” or “slip-ups” with males and females frequency engaging in uncommitted sexual behaviors. Indeed, using genetic testing of offspring, researchers have found that many of the species first thought to be “monogamous” like birds and gibbons actually participate in extra-pair copulations. It’s now more exciting to find a species that is actually sexually monogamous (such as the recent discovery of a monogamous frog). Evolutionarily speaking this is not surprising; we want to get it on with as many people as possible to pass on our genes and increase genetic diversity, while at the same time having enough resources to take care of our young. Therefore, it is possible that two competing systems co-evolved in humans: one that promotes monogamy (vasopressin, oxytocin and others) and another previously uncharacterized system that promotes sleeping around with as many people as possible. This predicts that our tendencies towards infidelity and sexual promiscuity could also be genetically encoded.

Is unfaithfulness really all in the genes? A new study published recently in PLoS ONE suggests that it might be, at least in part. The authors linked a certain variant of the dopamine D4 receptor gene to the propensity towards one-night stands (but not the actual number) and the number of sexual partners in those that were unfaithful (but not to unfaithfulness per se, although there was a trend towards significance). Interestingly, people with this variant have less dopamine D4 receptors in the reward centers of the brain and these receptors show less binding to dopamine, suggesting that these individuals might need more dopamine floating around to reach the same feel-good mood. It’s not a surprise then, that this variant has also been associated with a slew of other behaviors that increase dopamine release including addictions, risky behavior and novelty-seeking.

So, what does this mean? The authors are careful to point out that the dopamine D4 receptor gene should not be labeled the “cheating gene” or the “promiscuity gene” (although it already has) since having the variant does not necessarily mean that you will sleep around or be unfaithful. Many other genetic, environmental (alcohol) and cultural influences are likely to play into an individual’s decision to sleep around or cheat. In addition, the variant may be associated with a third confounding variable like being more honest about sexual behavior, more attractive, etc. Or it may simply be associated with risky behavior and novelty-seeking, increasing the likelihood of wanting uncommitted sex.

For now, I’d hold off on sending your significant other for genetic testing.