»Anyone who knows me also knows that I have a huge sweet tooth. I always have. My friend and fellow graduate student Andrew is equally afflicted, and living in Hershey, Pennsylvania – the “Chocolate Capital of the World” – doesn’t help either of us.
But Andrew is braver than I am. Last year, he gave up sweets for Lent. I can’t say that I’m following in his footsteps this year, but if you are abstaining from sweets for Lent this year, here’s what you can expect over the next 40 days.
Sugar: natural reward, unnatural fix
In neuroscience, food is something we call a “natural reward.” In order for us to survive as a species, things like eating, having sex and nurturing others must be pleasurable to the brain so that these behaviours are reinforced and repeated.
Evolution has resulted in the mesolimbic pathway, a brain system that deciphers these natural rewards for us. When we do something pleasurable, a bundle of neurons called the ventral tegmental area uses the neurotransmitter dopamine to signal to a part of the brain called the nucleus accumbens. The connection between the nucleus accumbens and our prefrontal cortex dictates our motor movement, such as deciding whether or not to taking another bite of that delicious chocolate cake. The prefrontal cortex also activates hormones that tell our body: “Hey, this cake is really good. And I’m going to remember that for the future.”
Not all foods are equally rewarding, of course. Most of us prefer sweets over sour and bitter foods because, evolutionarily, our mesolimbic pathway reinforces that sweet things provide a healthy source of carbohydrates for our bodies. When our ancestors went scavenging for berries, for example, sour meant “not yet ripe,” while bitter meant “alert – poison!”
Fruit is one thing, but modern diets have taken on a life of their own. A decade ago, it was estimated that the average American consumed 22 teaspoons of added sugar per day, amounting to an extra 350 calories; it may well have risen since then. A few months ago, one expert suggested that the average Briton consumes 238 teaspoons of sugar each week.
Today, with convenience more important than ever in our food selections, it’s almost impossible to come across processed and prepared foods that don’t have added sugars for flavour, preservation, or both.
These added sugars are sneaky – and unbeknown to many of us, we’ve become hooked. In ways that drugs of abuse – such as nicotine, cocaine and heroin – hijack the brain’s reward pathway and make users dependent, increasing neuro-chemical and behavioural evidence suggests that sugar is addictive in the same way, too.
Sugar addiction is real
“The first few days are a little rough,” Andrew told me about his sugar-free adventure last year. “It almost feels like you’re detoxing from drugs. I found myself eating a lot of carbs to compensate for the lack of sugar.”
There are four major components of addiction: bingeing, withdrawal, craving, and cross-sensitisation (the notion that one addictive substance predisposes someone to becoming addicted to another). All of these components have been observed in animal models of addiction – for sugar, as well as drugs of abuse.
A typical experiment goes like this: rats are deprived of food for 12 hours each day, then given 12 hours of access to a sugary solution and regular chow. After a month of following this daily pattern, rats display behaviours similar to those on drugs of abuse. They’ll binge on the sugar solution in a short period of time, much more than their regular food. They also show signs of anxiety and depression during the food deprivation period. Many sugar-treated rats who are later exposed to drugs, such as cocaine and opiates, demonstrate dependent behaviours towards the drugs compared to rats who did not consume sugar beforehand.
Like drugs, sugar spikes dopamine release in the nucleus accumbens. Over the long term, regular sugar consumption actually changes the gene expression and availability of dopamine receptors in both the midbrain and frontal cortex. Specifically, sugar increases the concentration of a type of excitatory receptor called D1, but decreases another receptor type called D2, which is inhibitory. Regular sugar consumption also inhibits the action of the dopamine transporter, a protein which pumps dopamine out of the synapse and back into the neuron after firing.
In short, this means that repeated access to sugar over time leads to prolonged dopamine signalling, greater excitation of the brain’s reward pathways and a need for even more sugar to activate all of the midbrain dopamine receptors like before. The brain becomes tolerant to sugar – and more is needed to attain the same “sugar high.”
Sugar withdrawal is also real
Although these studies were conducted in rodents, it’s not far-fetched to say that the same primitive processes are occurring in the human brain, too. “The cravings never stopped, [but that was] probably psychological,” Andrew told me. “But it got easier after the first week or so.”
In a 2002 study by Carlo Colantuoni and colleagues of Princeton University, rats who had undergone a typical sugar dependence protocol then underwent “sugar withdrawal.” This was facilitated by either food deprivation or treatment with naloxone, a drug used for treating opiate addiction which binds to receptors in the brain’s reward system. Both withdrawal methods led to physical problems, including teeth chattering, paw tremors, and head shaking. Naloxone treatment also appeared to make the rats more anxious, as they spent less time on an elevated apparatus that lacked walls on either side.
Similar withdrawal experiments by others also report behaviour similar to depression in tasks such as the forced swim test. Rats in sugar withdrawal are more likely to show passive behaviours (like floating) than active behaviours (like trying to escape) when placed in water, suggesting feelings of helplessness.
A new study published by Victor Mangabeira and colleagues in this month’s Physiology & Behavior reports that sugar withdrawal is also linked to impulsive behaviour. Initially, rats were trained to receive water by pushing a lever. After training, the animals returned to their home cages and had access to a sugar solution and water, or just water alone. After 30 days, when rats were again given the opportunity to press a lever for water, those who had become dependent on sugar pressed the lever significantly more times than control animals, suggesting impulsive behaviour.
These are extreme experiments, of course. We humans aren’t depriving ourselves of food for 12 hours and then allowing ourselves to binge on soda and doughnuts at the end of the day. But these rodent studies certainly give us insight into the neuro-chemical underpinnings of sugar dependence, withdrawal, and behaviour.
Through decades of diet programmes and best-selling books, we’ve toyed with the notion of “sugar addiction” for a long time. There are accounts of those in “sugar withdrawal” describing food cravings, which can trigger relapse and impulsive eating. There are also countless articles and books about the boundless energy and new-found happiness in those who have sworn off sugar for good. But despite the ubiquity of sugar in our diets, the notion of sugar addiction is still a rather taboo topic.
Are you still motivated to give up sugar for Lent? You might wonder how long it will take until you’re free of cravings and side-effects, but there’s no answer – everyone is different and no human studies have been done on this. But after 40 days, it’s clear that Andrew had overcome the worst, likely even reversing some of his altered dopamine signalling. “I remember eating my first sweet and thinking it was too sweet,” he said. “I had to rebuild my tolerance.”
And as regulars of a local bakery in Hershey – I can assure you, readers, that he has done just that.«
Given the deadly global rampage that HIV has been on for the past few decades, you’re all probably familiar with the virus. But you may not be aware that there are two types of HIV—HIV-1 and HIV-2—with the former being significantly more prevalent worldwide. The most common type of HIV-1 is then further divided into distinct subtypes, some of which are associated with a more rapid progression to AIDS. If these different viruses meet in an infected person, for example if someone infected with one subtype is exposed to a different one, they can exchange bits of their genetic material to create a new virus.
One of these so called “circulating recombinant forms” is currently spreading through Cuba, and it’s unfortunately extremely aggressive. Individuals infected with this hybrid virus, which is a mix of three different HIV-1 subtypes, progress to AIDS more than three times faster than average. Now, scientists have scrutinized this particularly pathogenic strain, which has yielded insight into the traits that have bestowed it with this deadly efficiency. The findings have been published in EBioMedicine.
Before HIV can get inside our cells, it first needs to bind to receptors on the surface called CD4. While this is an essential first step, it’s insufficient to get the virus inside. This is where anchoring points, called coreceptors, come in, which HIV also has to latch onto to gain entry. There are two coreceptors, CCR5 and CXCR4, and around 90% of newly transmitted HIV uses the former.
CXCR4-using viruses emerge in around 50% of individuals, but this usually takes around five years from infection. These viruses are associated with a more pronounced depletion of immune cells, but whether this shift in coreceptor preference is a cause or consequence of disease progression is unknown. Interestingly, however, the aggressive recombinant currently spreading through Cuba starts to use CXCR4 very early on in infection, and researchers think this is likely contributing to the observed rapid progression to AIDS.
To find this out, researchers examined 73 recently infected patients in Cuba, 52 who had rapidly progressed to AIDS within three years and 21 without AIDS. Then, they compared the blood of these individuals with 22 patients who had progressed to AIDS after the period typically expected, which is around 10-15 years without treatment.
They found that all those who had progressed to AIDS within three years of infection were infected with a recombinant called CRF19, which is a mixture of subtypes A, D and G. Interestingly, infection with A/D recombinants has previously been reported to result in rapid progression to AIDS, but no CRFs had been exclusively associated with rapid progression. Furthermore, those infected with CRF19 had abnormally high levels of an immune response molecule called RANTES, which acts by binding to CCR5. Without this coreceptor available for binding, CRF19 may have been forced to bypass that anchor point and go straight for CXCR4. Since the switch to CXCR4 usage is associated with progression to AIDS, this could explain why those infected with CRF19 developed AIDS so early on.
Another reason that CRF19 might be so pathogenic is that it has an enzyme, called protease, from subtype D, which is known to be very efficient. This enzyme helps the virus form mature particles, which is an essential stage in the virus life cycle.
It might seem like science fiction but a new implant which attaches directly to the spine could help paralysed people walk again
Paralysed patients have been given new hope of recovery after rats with severe spinal injuries walked again through a ‘groundbreaking’ new cyborg-style implant.
In technology which could have come straight out of a science fiction novel or Hollywood movie, French scientists have created a thin prosthetic ribbon, embedded with electrodes, which lies along the spinal cord and delivers electrical impulses and drugs.
The prosthetic, described by British experts as ‘quite remarkable’, is soft enough to bend with tissue surrounding the backbone to avoid discomfort.
Paralysed rats who were fitted with the implant were able to walk on their own again after just a few weeks of training.
Researchers at the Ecole Polytechnique Fédérale de Lausanne are hoping to move to clinical trials in humans soon. They believe that a device could last 10 years in humans before needing to be replaced.
The implant, called ‘e-Dura’, is so effective because it mimics the soft tissue around the spine – known as the dura mater – so that the body does not reject its presence.
“Our e-Dura implant can remain for a long period of time on the spinal cord or cortex,” said Professor Stéphanie Lacour.
“This opens up new therapeutic possibilities for patients suffering from neurological trauma or disorders, particularly individuals who have become paralyzed following spinal cord injury.”
Previous experiments had shown that chemicals and electrodes implanted in the spine could take on the role of the brain and stimulate nerves, causing the rats’ legs to move involuntarily when they were placed on a treadmill.
But this is the first study to show a simple gadget can help rats walk again and be tolerated by the body.
Scientists have struggled to find a device which will sit next to the spine or brain because both are surrounded by a protective envelope of tissue which the hard surface of implants can rub against, causing inflammation and scar tissue
However the new gadget is flexible and stretchy enough that it can be placed directly onto the spinal cord. It closely imitates the mechanical properties of living tissue, and can simultaneously deliver electric impulses and drugs which activate cells.
The implant is made of silicon and covered with gold electric conducting tracks that can be pulled and stretched. The electrodes are made of silicon and platinum microbeads which can also bend in any direction without breaking.
Writing in the journal Science, where the results were published, science writer Robert Service said: “Soft flexible nerves connected to unyielding silicon and metal – the combination has spawned many a Hollywood cyborg.
“The implants Lacour’s team created still have to be wired to the outside world to operate, but she and her colleagues are designing wireless versions of the technology. Watch out, Hollywood, reality is catching up.”
The research was praised by British scientists.
“The work described here is a groundbreaking achievement of technology, which could open a door to a new era in treatment of neuronal damage,” said Dr Duško Ilić, Reader in Stem Cell Science at King’s College London.
“Until now, the most advanced prostheses in intimate contact with the spinal cord caused quite substantial damage to tissue in just one week due to their stiffness.
“There is still a long way to go before we may see any practical use of such neuroprostheses in humans. But it may be that it is something that could potentially be developed for use in humans in the foreseeable future.”
Prof John Hunt, Head of Unit of Clinical Engineering, University of Liverpool, added: “This study in rats is an interesting one and it could have the potential to be quite promising in terms of being applicable to people with spinal injuries.”
The implant has been primarily tested in cases of spinal cord injury in paralyzed rats but researchers believe it could eventually be used in epilepsy, Parkinson’s disease and pain management.
The scientists are planning to move towards clinical trials in humans within the next few years.
The research was published in the journal Science.