Finding Mr. Right just got a lot harder

It’s hard being a young woman these days. Chivalry is dying, but many glass ceilings are still firmly in place. We’re supposed to have it all but sacrifice nothing, balancing choosing a career path and a life partner. We can delay having kids by putting our eggs in the freezer next to our vodka, but our similarly aging male partners’ sperm might handicap our chances of having healthy offspring, with higher risks for autism and schizophrenia linked to paternal age.

And now it turns out that hormonal contraception, or The Pill, our revolutionary defense against the inherent misogyny of biology, could be tricking us into choosing the wrong men.

Two studies led by Dr. Craig Roberts from the University of Stirling in Scotland have suggested that taking oral contraception can change your attraction to and preferences for men. In an initial study, Dr. Roberts and his team asked women who were about to go on the pill to rate the attractiveness of a selection of male faces, considering them as both short-term and long-term partners. They were then tested again approximately three months later to see if their preferences had changed. Sure enough, in the second test session women who had started hormonal contraception had significant shifts in their partner preferences, now preferring significantly less masculine-looking faces than they had three months earlier. Conversely, control women who had not started the pill did not differ in their choices from the first session.

In a follow-up study, real couples who had met while the woman was either on or off the pill were assessed for the male partner’s masculinity. This involved complex photo manipulation and judgment of the pictures by outside individuals, who ranked the male faces on features of masculinity. Though these methods are a bit fuzzy and convoluted, the researchers’ results (surprise surprise) matched those of the first study. That is, male partners of women who were already on the pill when they met were judged to be significantly less masculine looking than men whose female partners were not taking hormonal contraception.

Notable masculine features include squarer face-shapes, stronger jawlines and less prominent cheekbones, all of which are typical signifiers of higher levels of testosterone. The authors claim that this shift to preferring less masculine features is perhaps a transition towards subconsciously choosing more faithful or nurturing partners after starting contraception, which can be beneficial for long-term relationship success. However, a major problem with these partner preference shifts is that presumably at some point during a mature, adult, monogamous relationship women go off their contraception, potentially reversing back their partner preferences. This can lead to dissatisfaction in the relationship, female philandering, and some very awkward conversations: ”Sorry honey, you used to do it for me, but now I find you much too feminine for my liking.”

Another major concern is that genetically we are supposed to be drawn towards mates who are more dissimilar to ourselves. This is evolutionarily advantageous, as greater parental genetic variability reduces the likelihood of heritable diseases in the offspring. Basically, your children are less likely to be born with a genetic disorder if you and your partner’s DNA are more different. It has been proposed that some of the shifts in partner preferences after initiating oral contraception are actually towards men who are more genetically similar to you, which can be problematic, but no theories as to why this might be the case.

However, it’s a pretty big stretch to say that preferring men with slightly rounder faces means you’ve undergone a major change in your list of demands for your partner’s personality and genetic makeup (if you happen to have such a list for that). Also, the first study was only performed with 18 women in the experimental condition, which is a pretty tiny population for measuring significant differences in behavior. So the researchers conducted another follow-up experiment to investigate if these effects mapped onto real-world behavior. Researchers tested 2500 women (a much better sample size) in stable relationships who had started dating their partner while they were either on or off the pill, and compared them on several measures of relationship and sexual satisfaction.

Women who had first met their partners while taking oral contraception scored significantly lower on measures of sexual satisfaction and rated themselves less physically attracted to their partners than those women who had met their partners while not on the pill. However, the women taking the pill did have higher overall relationship non-sexual fulfillment and financial stability than those who were off. And in a related twist, women who were on contraception were actually less likely to have separated from their partners than women not on the pill at ‘partner choice’.

So what’s the take-away from this? Don’t take oral contraception and you’ll have better sex with a more attractive man, but will be more likely to break up with him in the future? Go on the pill and you’ll be dissatisfied sexually by your unattractive mate and your offspring will have genetic disorders, but at least you’ll stay together forever? Maybe. Or maybe being on the pill leads you to choose partners based more on long-term than short-term payouts. Or means that you have different priorities in your partner preferences to begin with. Either way, make the decision wisely, your future children may depend on it.

Everyone poops: A weight loss story

It seems like we are always looking for a quick and easy weight loss solution. We spend millions of dollars every year on gym memberships, workout equipment, dietary supplements and self-help books in the vain attempt to lose those last 5 (or 10 or 20) pounds. Unfortunately, most of these attempts fail miserably and we end up right back where we started, if not worse. But what if there was an easier way? What if there was one simple solution to losing all that excess weight for good? What if all it took was a stool transplant. Would you do it?

Yes, fecal matter. That embarrassing brown lumpy bodily expulsion. We learned from an early age that Everyone Poops, and now a recent study has hinted that with the right transfer, somebody else’s poop could help you lose weight.

But let’s not get too far ahead of ourselves and take a look at the real science first. The concept of a personal microbiome, a unique bacterial make-up as individual as our DNA, has been gaining traction over the last few years. Gut bacteria, or ‘microbiota’, have been implicated in everything from food allergies to obesity, with some studies suggesting that these bacteria may account for up to 20% of our differences in body weight. Stool samples are teeming with these microbiota, and previous studies have used fecal transfers to replenish lost essential bacteria that help fight infections after they’ve been wiped out with antibiotics.

Research from scientists at Cedars-Sinai Medical Center in Los Angeles has recently confirmed that some strains of bacteria can contribute to weight gain, helping people to retain and store calories more easily by aiding in the digestion of nutrients. These bacteria appear to make the stomach and intestines more productive, breaking down food faster and more efficiently so that more nutrients and calories can be absorbed. While this may have been beneficial to our hunter-gatherer ancestors, when food was scarce and mostly consisted of difficult-to-digest plants and animals, today it may be contributing to our problems with over-nourishment and obesity. In the current study, people with greater levels of these bacteria, determined either through stool samples or breath tests measuring hydrogen and methane – by-products of this nutrient break-down – had higher BMIs and body fat percentages than those with lower trace products of the bacteria.

But if your breath tastes especially methaney, don’t despair. According to recent research, there are now several ways to change your gut microbiota.

Physicians have long used gastric bypass surgery to aid in weight loss in cases of extreme obesity. The procedure involves removing up to 80% of an individual’s stomach and can result in weight loss of 75% of excess body weight. This dramatic success was initially thought to be driven by the reduction in stomach size, resulting in a lower capacity for consumption and absorption calories. Simply put, the smaller your stomach, the less food you can eat. However, new evidence suggests that a shift in gut bacteria may also aid in this change.

The microbiota of obese people is markedly different from those of lean individuals, contributing to and perpetuating weight problems. This bacterial profile is partly influenced by what we eat, and it turns out that changing the size of the stomach and intestines can also dramatically alter the make-up of these bacteria. A study published in Science Translational Medicine by researchers from Massachusetts General Hospital recently demonstrated this effect in mice, hinting that it also might apply to people.

In the study, animals who had undergone gastric bypass operations showed not only significant weight loss, but also a dramatic change in microbiota, potentially both resulting from and furthering their weight-loss. Notably, this change was larger and more stable in mice who had had the surgery than in those who lost a similar amount of weight through diet changes, but without the operation. The bypass mice also had greater fecal fat content (yes, we’re back to poop again), suggesting that the new gut bacteria make-up was limiting the break-down and digestion of fat, meaning more was passed through the body without being absorbed.

Previous research has suggested that body weight and fat can also be influenced by transferring lean animals’ intestinal bacteria into obese mice, and vice versa. To test this effect in the current study, gut bacteria from the bypass mice were inserted into new animals through intestinal content transfers – i.e. fecal matter transplants. Sure enough, these ‘donations’ from the bypass mice resulted in significant reductions in body weight and fat levels in the receiving animals, but interestingly did not affect food intake.

As fascinating as these results are, some important questions remain. Firstly, is this a long-lasting effect? Could stool bacterial transfers from lean individuals be a long-term solution to obesity, or would these effects fade away as the transferred super-bacteria die off and are replaced by the host’s natural ones? To date, no studies have followed up these effects long-term, so this remains to be seen. Also, like much innovative scientific research, these results come with ethical questions to consider. Does having a different type of gut bacteria change our responsibility for our own weight and healthy diet? And should we all receive an injection of lean bacteria to prevent future obesity and related health problems?

So what do you think, would you do it?

The second piece of chocolate

Imagine you have a piece of chocolate. Unwrap it, place it on your tongue. Savor its decadence as it melts in your mouth; relish the bitter and sweet coating your taste buds; indulge in its creamy texture. As the chocolate dissolves, signals are sent throughout your body. Chemicals are released, reinforcing its rewarding properties and preparing your body for the rush of sugar it is about to receive. You swallow. Immediately you want another piece.

The pleasure of eating is one of our most natural joys, be it savoring a perfectly cooked steak or delighting in that melt-in-your-mouth chocolate. But with the rise of obesity and related maladies – particularly cardiovascular disease, hypertension and type-II diabetes – such simple pleasures have been perverted, pathologized by experts and classed as a source of harm. With nearly 25% of English adults qualifying as obese, and with ensuing costs to the NHS reaching £5.1 billion each year, the UK is facing a self-induced public health pandemic. But how has this happened? And why can’t we all just put down that second piece of chocolate?

Added sugars have become the focus of widespread concern among doctors and researchers, their effects on our waistlines, livers, and even our brains, giving cause for alarm. Obesity specialist Dr. Robert Lustig has emerged as a crusader for the anti-sugar movement, contending that sugar, not fat, is behind the dramatic rise in ‘western diet’ conditions over the past 30 years. The problem stems from the way our bodies metabolize fructose – half of the refined sugar molecule, sucrose – as opposed to pure glucose, which makes up the other half and is found in foods like potatoes and white bread.

Glucose is metabolized by all cells in the body, whereas fructose is primarily processed by the liver. If the liver cannot adequately break down sugar into energy it is converted into fat, and the faster the body receives fructose, the more likely this is to happen. High fructose sugar solutions, like fizzy soft drinks, are particularly prone to this fat conversion, providing high volumes of fructose that reach the liver much more quickly. This inability to break down sugar and the subsequent rise in liver fat is believed to be at the root of insulin resistance, the main deficiency underlying type-II diabetes.

But regardless of doctors’ warnings and the evidence that increased sugar consumption leads to obesity, as well as liver and heart disease, our sugar intake continues to rise. This may be due to the seemingly addictive qualities of high-sugar foods themselves. For despite our best intentions to cut out the cake, doing so rivals quitting smoking in terms of difficulty. New research indicates that foods high in fat or sugar may qualify as addictive substances, causing similar neurochemical changes in the brain as drugs of abuse.

Researchers at Princeton University have demonstrated this phenomenon by intermittently exposing rats to a sucrose solution in addition to their regular food. After a month, rats began to show binge, craving and withdrawal-like behaviors for sucrose, self-administering extremely large quantities when it was available. Adaptations similar to those seen in cocaine-addicted animals emerged in the rats’ brains, with surges of dopamine released during a binge – a process linked to feelings of reward and novelty, and a key facet of drug addiction. An increase in craving was also seen in the test animals, demonstrated by greater sucrose-seeking when deprived of the solution, even in the face of punishment. Additionally, rats experienced withdrawal-like symptoms when the sugar was removed, exhibiting tremors, head-shakes and signs of anxiety and aggression. Such behavior is typically seen in animals going through opiate withdrawal, and is caused by the release of endogenous opioids in the brain by high-sugar foods, reinforcing their hedonic characteristics and creating a withdrawal effect when removed.

Given sugar’s apparently addictive properties, one proposed response to the obesity epidemic is to regulate its availability in much the same way as tobacco and alcohol. Labeling foods high in sugar and fat as ‘addictive’ could potentially remove the stigma attached to being overweight, re-characterising it as a complex medical condition rather than simply one of personal weakness and poor self-control. Furthermore, tougher regulations on the advertising and availability of junk food might help to reduce the proliferation of cheap high-fat/high-sugar snacks that has made diet control increasingly difficult. However, taking responsibility for diet out of the hands of individuals also diminishes personal accountability and the imperative for each of us to make positive food choices. The fast food industry certainly isn’t helping us to lose weight, but it’s also not forcing the food down our throats. Should we be trusted to control what we put into our bodies, or do we need someone to stop us from taking that second piece of chocolate?

*So this post is a bit cheeky. I originally wrote this as a submission for a writing competition, but seeing as how it was never published, I figured it made an apt piece in honor of New Year’s resolutions!

(Thanks to Paul Sagar for help in editing the original piece.)

A Thanksgiving ode to tryptophan

My favorite holiday is on Thursday. And while I can’t be at home in the States to celebrate, being an ex-pat at Thanksgiving does have its perks, as I get to attend multiple alternate feasts over the weekend. That means twice the stuffing, twice the cranberries, twice the turkey, twice the tryptophan.

Yes, tryptophan. That infamous amino acid we use to justify dozing off during our aunt’s vacation slideshow after the big meal. Tryptophan is an essential amino acid, a protein precursor that the body uses to build various chemical structures. This includes serotonin, one of the primary neurotransmitters in the brain that is involved in everything from decision-making to depression. Serotonin is also a precursor to melatonin, which is important in sleep and wakefulness and is where the tryptophan-tiredness link comes in. However, despite the popular neuro-myth, turkey is actually no higher in tryptophan concentration than other types of poultry. Numerous different plant and animal proteins provide us with our daily doses of tryptophan, with sunflower seeds, egg whites and soy beans having some of the highest concentrations of the amino acid. In fact, turkey comes in at a measly 10th on the list of tryptophan sources.

Instead, the relation between eating and sleeping seems to be more dependent on the amount of food consumed, rather than the type we eat. Insulin is released after every meal, particularly ones high in carbohydrates, and the more carbs consumed, the more insulin is produced. This increase then changes the chemical levels in our bloodstream, affecting the re-uptake and release of various amino acids. Ultimately these changes result in greater amounts of tryptophan crossing the blood-brain-barrier and being taken up into the brain. There the tryptophan is converted to serotonin, some of which is also metabolized into melatonin, causing our postprandial nap.

Tryptophan’s influence on serotonin levels doesn’t just affect sleep cycles. The link between depression and low serotonin levels is well established, and tryptophan supplements have been suggested as less invasive treatments for the disorder. Unfortunately these studies have been mostly unsuccessful to date, as mild modifications of tryptophan seem to have little to no effect on mood in most individuals. However, it is possible that people with low endogenous levels of tryptophan due to specific genetic profiles may be more susceptible to the chemical’s effect on mood, and current research is still ongoing in the matter.

So regardless of whether it’s turkey, stuffing or sweet potatoes you prefer, remember to load up your plate during Thanksgiving to get those happy drowsy effects later. It may just help you feel a little bit calmer, and prevent some of the Black Friday mayhem the next day.

Weed be better off smoking our parents’ pot

We’ve all heard our parents say it*: “Back in my day, dope was much better than it is now. It wasn’t nearly as strong as what you kids smoke today.”

Like much of the advice our parents give us (like always take out your contacts before you go to bed), this one is also true. The THC (tetrahydrocannabinol – the primary psychoactive compound in cannabis) concentration in marijuana has increased by as much as 12% over the last 30 years. This rise in THC levels is related to increases in the subjective ‘high’ feelings associated with smoking cannabis, like changes in perceptual sensations, contentedness, and increased appetite. However, THC is also linked to many of the negative consequences of cannabis use, including risk for dependence, attentional bias or distraction, impaired memory and cognition, and the potential emergence of psychotic symptoms.

Alternatively, CBD (cannabidiol – one of the other major chemicals in cannabis that works by increasing endogenous cannabinoid levels in the brain) is associated with the anxiolytic or anti-anxiety effects of marijuana. Additionally, it is thought to act as a protective factor against many of the negative effects the drug can have, including the development of abuse, cognitive impairments, and even psychotic symptoms.

Unfortunately, in addition to the high levels of THC seen in today’s cannabis, there is also a significant depletion of CBD. ’Skunk’, as it is referred to by users and dealers alike, is the strain of this new high-THC, low-CBD cannabis that is flooding the marijuana market. And it is this drug that is thought to be at the root of the increase in cannabis dependence diagnoses seen over the last decade.

Recent changes in policy and public perception of the risks associated with cannabis have also resulted in an increase in use, particularly among adolescents and young adults, with roughly 50% of high school students reporting having used the drug at some point in their lives. However, despite a previous belief that cannabis was not addictive, there has also been a substantial increase in the number of users seeking treatment for dependence, and nearly 11% of current users qualify as addicted. Skunk smokers in particular are more likely to experience cravings for the drug, go through their stash in shorter amounts of time, and have greater attentional bias to cannabis cues.

Professor Val Curran’s group from University College London has been leading the charge on research into the effects of cannabis use, comparing recreational and chronic smokers, and studying the varying effects different strains of cannabis have on the brain. Her group is particularly interested in comparing skunk to THC-CBD strains, and they have discovered much of the evidence for the protective effects CBD has against the development of psychosis and dependence. CBD’s action upon the endogenous cannabinoid anandamide seems to be behind the reduction in psychotic experiences in regular smokers, and CBD has even been looked at as a potential treatment for schizophrenia, reducing psychotic symptoms as effectively as some of the anti-psychotic drugs currently prescribed. THC-CBD users also show less distraction to marijuana stimuli than skunk smokers, and they report significantly reduced feelings of craving. There were also no differences in the subjective intoxication effects of smoking either skunk or THC-CBD, indicating it does not alter the psychoactive properties of the drug.

So the question is, where has all the CBD gone? Modern day growing methods using indoor marijuana farms have greatly decreased the risk of detection for cannabis producers by circumventing the need to import cannabis internationally. Cannabis greenhouses also guarantee a more reliable crop, as they are not dependent on changes in weather patterns. However, the 24-hour lighting used in these farms results in an inadvertent destruction of the CBD levels in the plant. Thus, these new strains not only have increased potency with higher THC contents, they also have reduced protective factors against the drug’s negative effects. In the producers’ eyes, these are just additional economic advantages to growing on an indoor farm, as more dependent users who go through the drug more quickly will result in more cannabis being sold.

These changes in potency raise interesting questions regarding the recent legalization of recreational and medicinal marijuana use in some states. Most pressingly, where and how is this cannabis being produced? And what are the differing levels of THC and CBD present in it? Also, would it be possible to better control cannabis production to avoid its addictive or psychotic-inducing effects? And should we start to think about prescribing CBD to patients currently suffering from THC dependence?

While the developments in cannabis policy may potentially reduce the harm caused to individuals from incarceration or criminal records for minor possession, in terms of the potential psychological effects caused by the drug, it appears we’d be better off smoking our parents’ pot.

*Apologies to my parents, who have never actually uttered the above phrase.

**Title pun credit to Claire Gillan.

Thought-controlled robot arms: Welcome to the future!

It’s the year 2012, and while we don’t all have jet packs or flying cars, there have been some pretty incredible scientific discoveries as of late. Two amazing studies in particular have come out involving advances in spinal cord injury rehabilitation. The first helped paralyzed rats to walk again, and in the second a tetraplegic woman used a thought-controlled robotic arm to take her first self-directed sip of coffee in 15 years.

The first study, published in Science by a Swiss research group, used rats to study physical rehabilitation in paraplegic animals. The researchers partially severed the spinal cords of a group of rats, paralyzing their hind-legs but crucially sparing some of the nerve tracts up to the brain. They then stimulated the spinal cords of these animals in the affected region with an electro-chemical current, hoping to excite the remaining nerve cells. The idea behind this is that if you can activate somatosensory signals (the sensations of touch and position of the body) in the affected limbs, you can help rewire the brain to potentially encourage firing of motor neurons as well.

Researchers also fitted the rats with a prosthetic harness that helped support the animals and placed them on a tiny treadmill, while simultaneously stimulating their injured spinal cords with the electro-chemical signal (the article has amazing videos of this here). By zapping the spine with this current and artificially moving the animals’ legs, it is possible that any lingering neurons involved in these motor and sensory regions will be stimulated, and possibly re-wire to facilitate further repair and improve locomotion. Sure enough, after just three weeks of this training program some of the animals were able to take steps voluntarily, and after six weeks all of the rats could walk with help from the stimulation. After two more weeks of training these formerly paralyzed rats were even able to go up stairs and jump over obstacles!

Confirming the researchers’ theory of assisted neurogenesis, the rats who had undergone the training program had significantly more new neurons and connections from the spinal cord to the motor area of the brain than animals who had not been trained.

In the second and even more fantastical study, two patients with tetraplegia (complete paralysis of the body) were able to self-direct a robotic arm using only their thoughts. Led by Dr. Leigh Hochberg at Brown University and published in the journal Nature, scientists implanted an electrode into the motor area of the paralyzed individuals’ brains. The patients practiced for months, training the computer chip to read their motor neurons’ signals by imagining moving their arms in various prescribed motions. The chip learned to decode the relevant firings from these cells, measuring the corresponding output from each neuron for the specified movement, and then used these signals to comunicate with a computer and direct a nearby robotic arm.

Starting with just simple point and touch actions, the patients trained the system on increasingly more difficult motions involving precise speed, force and direction. By the end of the study, the communication and interpretation of one of the patient’s thoughts was so well coordinated she was able to use the robotic arm to grasp a cup, raise it to her lips and drink through a straw (there are some pretty amazing images of this as well).

I’m going to repeat that: with the help of science and a microchip, this woman controlled a robot with her mind!

So while I’m still waiting for my jet pack, these studies are pretty exciting examples of advances in health-science research, showing just how far science has come and giving us a glimpse into the next generation of neuro-engineering. Welcome to the future.

If I can’t remember it, it didn’t happen: A susceptibility for alcohol-induced blackouts

As anyone who’s ever taken an Alcohol Edu course (or been 21 in the last decade) knows, consuming too much alcohol can cause memory loss, colloquially known as a “blackout”. This anterograde amnesia stems from an inability of the brain to form new long-term memories and is caused by a disruption in the GABA and NMDA receptors in the prefrontal cortex (PFC) and medial temporal lobes when drinking.

First, for those of you who skipped (or drank) your way through your alcohol education, a brief reminder on the effects of alcohol on the brain. GABA is a primary inhibitory neurotransmitter, acting to decrease the likelihood of a cell’s firing. Alcohol acts as a GABA agonist, elevating levels throughout the brain and therefore diminishing the rates of firing in normal cellular processes. At high levels, alcohol also acts upon glutamate NMDA receptors, one of the main excitatory neurotransmitter systems. Alcohol works as an NMDA antagonist, blocking the NMDA receptors and preventing glutamatergic activation, further inhibiting neuronal functioning. This inhibition particularly occurs in the PFC, medial temporal cortex and the parietal lobe, primary targets of alcohol in the brain. In the hippocampus in particular, an area in the medial temporal cortex crucial to memory formation, this inhibition can result in a disruption of long-term potentiation, a cellular process involved in the consolidation of short-term to long-term memories.

Alcohol’s effect on the PFC also impacts memory ability, as short-term memories are maintained there while they are being worked on or rehearsed. However, when attention shifts to a new stimulus this memory must be consolidated into a more stable long-term version via cellular activity in the hippocampus, or else it will be discarded and forgotten. Alcohol’s inhibition of the PFC via its effects on GABA and glutamate can disrupt the maintenance of these short-term memories, decreasing the likelihood of consolidation and preservation. The dampening of firing in the PFC is also attributed to the behavioral disinhibition that so commonly succeeds alcohol consumption, as the PFC can no longer inhibit or control impulses as well.

Now, on to the exciting bit! In individuals who regularly experience alcohol-induced memory loss, or a blackout, it is the contextual memory that seems to be most impaired. This refers to the details surrounding an experience, such as where, when and with whom the event occurred. However, blackouts seem to affect some drinkers more than others, and are not necessarily determined by the amount of alcohol that an individual consumes. Simply put, you either blackout when drinking large amounts of alcohol or you do not.

Published online this week in Alcoholism: Clinical and Experimental Research, psychologists from the University of California, San Diego and the University of Texas, Austin have recently confirmed this urban drinking legend by testing 24 regular binge drinkers, 12 of whom admitted to blacking out on a regular basis, reporting on average two blackouts per month, and 12 who drank comparable amounts of alcohol but declared no memory problems when drinking. Both groups were matched on their typical alcohol consumption, averaging 3 drinking days per week and consuming 4-5 drinks at a time on a typical day when drinking. Both groups also had comparable binge tendencies, consuming 10 or more drinks on occasion over the previous 3 months.

Participants were tested on a contextual memory task using functional magnetic resonance imaging (fMRI) both when sober and after drinking to a blood alcohol content of .08, the legal limit in the United States, typically 3 drinks for a male and 2 for females. During both the sober and intoxicated trials, participants performed equally well in their behavioral scores, recalling similar amounts of information regardless of their blackout group status. Groups also did not differ in their response times on the task during either condition, however both groups recalled significantly fewer trials when intoxicated and were significantly slower than when sober.

In the imaging analysis, there were no differences in activation levels between the groups during either encoding or retrieval for the sober condition of the task. However, when intoxicated, both groups demonstrated significantly less activation in the right frontopolar PFC during retrieval. The blackout group also had significantly less activation during both the encoding and recall portions of the experiment after consuming moderate amounts of alcohol as compared to the non-blackout group. Specifically, participants with a history of blacking out showed less activation in the left frontopolar PFC during encoding, and decreased activity in the right posterior parietal cortex and the bilateral dorsolateral PFC during retrieval as compared to their non-blackout contemporaries. This fronto-parietal network is implicated in attentional maintenance and inhibition, as well as working memory and executive control, suggesting that there could be greater difficulties in these skills in the blackout group when drinking.

The researchers speculate that the decrease in activity in the frontal pole during intoxication is indicative of an alcohol-induced impairment in executive functioning in both groups, particularly in regards to working memory and cognitive maintenance. The additional decrease in activation in the fronto-parietal network seen in the blackout group also suggests a greater disability in executive functioning and memory maintenance in these individuals when drinking. However, it is notable that there were not any significant behavioral differences between the two groups in total memory recall, particularly during the intoxication condition.

While it is reassuring that there were no impairments in either group during the sober condition, the drinking results do seem to suggest that there may be underlying problems with memory and executive functioning in those individuals with a proclivity for forgetting, which could emerge after more chronic drinking behaviors. Why some people are predisposed towards these additional memory impairments is still unclear, but there does seem to be something different in the brains of those who blackout regularly that is not just dependent on the amount of alcohol they drink.

(Insert poor taste joke about drinking away your memory problems here.)

Frankenstein research methods in multiple sclerosis treatments

I recently attended a fascinating lecture by Cambridge neuroscientist Robin Franklin on progenitor cells (“neural stem cells”) and their treatment potential in neurodegenerative diseases, such as multiple sclerosis (MS). The progressive form of MS, which follows from the relapsing-remitting version, stems from a decreasing ability of oligodendrocyte cells and their crucial myelin sheaths to be regenerated after they are destroyed through the course of the disease. Dr. Franklin’s lab studies cell remyelination, specifically focusing on oligodendrocyte precursor cells (OPCs), which are a form of progenitor that can evolve into oligodendrocytes to replace the damaged cells and sheaths. However, as an individual ages, these cells have a greater difficulty differentiating and do not regenerate as efficiently, which is most likely the cause in the transition to the progressive form of the disease. Dr. Franklin’s lab has used parabiosis to study the effects of aging on progenitor cell differentiation, the amazing science fiction-esque research method of fusing two mice together (in this case young and old), enabling them to share blood flow. From this research, Dr. Franklin has provided the most compelling evidence to date that decreases in crucial blood proteins as an individual ages are behind the increasing disability in remyelination and disease progression.

But let’s take a step back and do some defining, as I’ve just introduced a lot of jargon in that first section. Until only the last few decades, it was commonly thought that brain structure was relatively stable through adulthood, the window of neurogeneration and plasticity closing after adolescence. However this myth has been debunked, and there has been a revival in research on neural plasticity in adulthood and its potential treatment implications for individuals suffering from stroke, traumatic brain injury, and neurodegenerative diseases.

Multiple sclerosis (MS) is a neurodegenerative disease that consists of the breakdown of myelin sheaths, the protective coatings that surround cell axons and make up white matter tracts, enabling more efficient signal transmission between cells. This is in contrast to other neurodegenerative diseases, such as Huntington’s or Parkinson’s disease, which stem from the death of gray matter neurons themselves. These myelin sheaths originate from oligodendrocyte cells, bizarre looking neurons that consist of a cell body and up to 80 projections of giant wrap-around sheaths coming out of each arm. These sheaths encase and protect neighboring cell axons, however in MS both the sheaths and the oligodendrocyte cells become damaged, eventually breaking apart and dying.

Fortunately, the brain contains its own version of stem cells, early stage neurons called progenitor cells that have the potential to develop into a variety of different types of mature neurons. These progenitor cells are particularly adept at evolving into oligodendrocytes, and thus in the early stages of MS these lost cells can be replaced relatively easily. This depletion-repletion process explains the relapsing-remitting course of the early stages of MS. However, as the disease progresses it becomes increasingly difficult for these oligodendrocytes to regenerate, stemming from an increasing inefficiency in differentiation of the progenitor cells. This turn of events seems to define the later stage of progressive MS, though why this decline occurs has been unclear.

Enter Dr. Franklin and his team of researchers. Published recently in Cell Stem Cell, Dr. Franklin’s group used parabiosis to determine that the decreasing efficiency of cell regeneration was caused by an increase in age. Comparing heterochronic (young and old mice joined together) with isochronic (young-to-young or old-to-old) pairs, researchers damaged the myelin in the spinal cord of the older animals using a local toxin injection, and measured subsequent levels of both oligodendrocyte precursor cells (OPCs) and oligodendrocytes themselves. After 14 days, the levels of OPCs in the older damaged mice in the heterochronic pairs was significantly greater than those in the older isochronic animals, and at 21 days the levels of mature oligodendrocytes in old heterochronic animals were equivalent to those in young isochronic pairs. Both of these results were associated with an overall increase in myelination in the damaged heterochronic-old animals as compared to the isochronic-old pairs.

This improvement in regeneration seems to stem from an increase in differentiation of the already existing progenitors in the old mice, rather than a pilfering of these cells from their young counterparts. Instead, by joining together the vascular systems of the young and old animals, the older mice were able to benefit from increased levels of proteins and cells, such as macrophages, that signal the need for differentiation in the progenitors, enabling them to once again trigger the transformation process into full-fledged oligodendrocytes.

In his talk, Dr. Franklin was quick to point out that this was not a therapeutic study, but that it instead shows a pharmacological approach towards regeneration of oligodendrocytes for remyelination in MS may be promising going forward. These results suggest that it is not an influx of new progenitor cells that is needed in older individuals, but instead an enhancement of the signalling cells that make these transformations possible. This would of course be a far easier clinical undertaking than surgically fusing together young and old patients, and provides one of the first bits of evidence for treatment options in actually repairing the damage caused by neurodegenerative diseases.

Forget the stair master, brown fat is where the burn is at

There has been a flurry of articles recently about the rise in research on brown adipose tissue (BAT), endogenous body fat that contains higher levels of mitochondria and is used to help keep the body warm. Until only three years ago, this holy grail of body tissues (“good” fat that burns significantly more calories and can help rid the body of “bad” fat) was thought to exist only in rodents, where it was more commonly seen in the young and in thinner animals. However, BAT has also been seen in human infants, important in helping to keep newborns warm as they can not shiver to create their own body heat. BAT was thought to gradually disappear as individuals aged, but it is now believed that adults can retain small levels of their brown fat from childhood, with thinner individuals maintaining more, and that exercise can aid in this retention

How BAT promoted weight loss was not understood until recently. Researchers from Canada shed light on this process using PET-CT scans to identify the metabolic processes involved in BAT. Published this month in the Journal of Clinical Investigation, researchers subjected participants to acute cold exposure by placing them in a special liquid thermo-controlled suit at a temperature of 18 degrees Celsius (64 degrees Fahrenheit) for 90 minutes. During the course of this exposure, brown fat in the upper back experienced a significant increase in cell metabolism while working to keep the body warm, a process dubbed “cold-induced nonshivering thermogenesis”. Researchers hypothesized that this increase in BAT metabolism was initially fueled by elevations in extracellular glucose and fatty acid uptake, but that when these levels were depleted the tissue began drawing on stores of intracellular triglycerides, meaning that BAT was burning off lipid reserves during cold exposure.

As such, total energy expenditure of participants increased during the study by a whopping 80%, resulting in an average burn of an additional 250 calories. Curiously, there was no significant interaction between the amount of brown fat an individual had and caloric expenditure despite a wide variability in BAT levels, though this could be due to the small study sample size, involving only six participants. There was an interaction between BAT and thermogenesis though, with the added increase in metabolism helping to keep an individual warmer longer, and the more brown fat a participant had the longer and colder conditions he or she could stand before starting to shiver.

A second study on brown fat looked at a more elusive type whose production is promoted through exercise. Published this month in the journal Nature, researchers at the Dana-Farber Cancer Institute discovered a new hormone, christened irisin, that seems to help transform white fat into brown fat. This production is dependent upon the transcriptional co-activator PGC1-α, a protein found in muscle tissue that is generated during exercise and involved in metabolism, cell genesis, and protection against muscle atrophy.

Knowing its vast beneficial effects, scientists bred mice to have elevated levels of PGC1-α to determine its influence on BAT and energy expenditure. Although the increase in protein had no effect on either brown or typical white adipose tissue, there were effects in a special type of subcutaneous white fat that is more susceptible to “browning”. This process involves increases in levels of the protein UCP1, which is highly active in brown fat cells and is involved in thermogenesis. These same effects also seem to occur following a regular exercise program in mice, facilitated by changes in mRNA expression induced by increases in PGC1-α and subsequent protein production.

Through several elaborate experiments, researchers were able to narrow down the proteins to those affected by the gene expression of FNDC5, including the newly discovered irisin. Irisin is significantly elevated in both mice and humans after exercise, and appears to be the key ingredient in the expression of UCP1 in the transition from white to brown fat. Direct injections of the protein resulted in increased levels of UCP1 in subcutaneous white fat, as well as subsequent increases in metabolism and small decreases in body weight in obese mice 10 days after exposure.

While both of these studies are still in their infancy, their potential implications for future research are very exciting. In the mean time, if you want to lose weight try going for a run, the benefits may be twofold. Alternatively, if you’re too lazy to work out you could try sitting outside in the cold for a while.*

*Please note, I do not actually recommend this as a safe or valid weight loss plan.

That Diet Coke isn’t so diet anymore

While everyone is working on their New Year’s resolutions for 2012, either making them or not breaking them, I thought it would be a good time to write about a trio of articles on sugar and artificial sweeteners and their respective health consequences.

A piece published in New York Times magazine several months ago raised the alarm on the extreme health detriments of our sugar habits. Author Gary Taubes cited Dr. Robert Lustig, a researcher in pediatric obesity and hormone deficiencies, as promoting the idea that sugar, not fat, is the main cause for the dramatic rise in type 2 diabetes, hypertension and other “western diet” diseases seen in the last 30 years. These particular detriments stem from the way our bodies metabolize fructose (which makes up half of the refined sugar molecule sucrose), as opposed to pure glucose, which makes up the other half and is found in foods such as potatoes and white bread.

Glucose is metabolized by all cells in the body, whereas fructose is primarily processed by the liver. If the liver cannot adequately break down the sugar (both fructose and glucose) it receives into energy, it is converted into fat. This is more likely to occur if the liver becomes overloaded by the fructose in sucrose solutions, such as in high fructose corn syrup which has a greater concentration of fructose to glucose. The more and faster the body receives the fructose the more likely this is to happen. Therefore, drinking a sugary beverage, such as soda or even fruit juice, results in an even greater spike in fructose as it reaches the liver much more quickly. These drinks place a greater strain on the body than a raw piece of fruit, a “pure” form of fructose, which contains fiber and is digested much more slowly. This failure to break down sugar and the subsequent rise in liver fat is believed to be at the root of insulin resistance, the main underlying deficiency in metabolic disorders such as type 2 diabetes and heart disease.

It is undeniable that as our sugar consumption increases, so do our rates of obesity, diabetes and heart disease. Currently the average American consumes roughly 90 pounds of added sugar a year, and recently non-sugar sweeteners have been proposed as an alternative to sugar and high-fructose corn syrup to help reduce these rates. However two studies from the University of Texas: San Antonio presented at the American Diabetes Association’s Scientific Sessions suggest that these changes might not provide any real benefit.

The first, a longitudinal health study, measured participants’ waist circumference over a ten-year period. They discovered that diet soda drinkers had an almost 70% increase in waist circumference over this time, and those who reported drinking more than two diet soft drinks every day had waist circumference increases 500% greater than individuals who did not consume any diet drinks. These results remained even after controlling for variables such as starting circumference, diabetes, age, sex, smoking status, physical activity levels, and neighborhood of residence.

The second study assessed the effect of aspartame on a high fat diet in mice. One group received food chow with added corn oil and aspartame, the other just the additional corn oil. The group that consumed the extra aspartame had significantly higher glucose levels, but similar insulin levels than the mice who only received the high fat diet. This signifies severe consequences of a fake sweetener diet on diabetes, as blood sugar levels were elevated but insulin (which lowers blood sugar) was not compensatorily raised. This suggests that diet sodas and other foods made with fake sugar could actually lead to an increased risk for developing type 2 diabetes compared to a high fat diet alone.

So if anyone is still looking for a resolution this New Year, perhaps try cutting back on your soda consumption, both regular and diet. Your liver will thank you.