A Hippo on Campus

Editor's Selections: The Smell of Fear, Placebo genes, Race and penis size and Mapping the Brain

2012-10-29T15:31:00.000+11:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

The Scorpion and the Frog's Miss Behavior sniffs out a study on the 'Smell of Fear'.
Steven Novella discusses recent reports of the 'placebo gene' at Science-Based Medicine.
Scott McGreal from Eye on Psych unravels a new study looking at racial background and penis size.
And Ferris Jabr discusses how DNA barcoding may help scientists map the brain.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Psychedelic DMT, Facebook stalking and 'Vaccine Injury'

2012-10-15T22:31:00.000+11:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Eye on Psych takes a two part look at the psychedelic world of Dimethyltryptamine (DMT) in 'DMT, Aliens and Reality Part 1 and Part 2.
Gaines on Brains discusses the cons of our Facebook stalking ways.
And a number of bloggers take those trying to link vaccinations and shaken baby syndrome to task:

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Gangam Style, beautiful brains, paradoxical obesity and the IgNobel Prize winners

2012-10-01T22:18:00.001+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Psysociety's Melanie Tannenbaum explores the psychology behind 'Gangam Style'.
BrainBlogger, Jennifer Gibson discusses our new found attractions in 'Genlemen prefer brains'.
Harriet Hall dissects 'The Obesity Paradox'.
And Scicurious talks us through the latest IgNobel winning research:

This post was written by Andrew Watt for A Hippo on Campus.

The Stigma of Dementia

2012-09-27T10:32:00.000+10:00

Last Friday, September 21st, was World Alzheimer's Day and in keeping with recent tradition it was also the day that Alzheimer's Disease International released their 2012 Report. This year's report focused on the stigma of dementia and included results from an international survey of people with dementia and carers as well as a collection of essays from people in the broader Alzheimer's community, including myself. A reproduction of my essay can be found below and the full World Alzheimer Report 2012 can be downloaded here.

There are few things more frightening than the thought of losing your mind. Losing those last shreds of awareness that tether you to your life and the people around you. If you’re lucky this notion will remain just that, a fear. An abstract thought that acts to occasionally cajole you into exercising more or eating better. But for others, a diagnosis of Alzheimer’s disease or dementia can turn this fear into a reality, taking a healthy mind and slowly stealing it away as they watch it happen [1]. There are currently an estimated 36 million people living with dementia worldwide [2]. Thirty-six million people quietly slipping away from both themselves and the loved ones who surround them. In many cases these individuals are struggling with more than just their condition alone, they are struggling with the profound stigma that remains affixed to a diagnosis of dementia.

The stigma associated with dementia adds an additional burden to the already heavy load carried by all those who are affected. Emanating either externally, from the wider population, or internally, from the affected individuals and carers themselves [1], such stigma acts to reduce people affected by dementia ‘from a whole and usual person to a tainted and discounted one’ [3].

Until recently my father, Alan, was one of the many individuals living with dementia. He was diagnosed with younger-onset Alzheimer’s disease at the age of 54, although we would later discover that this diagnosis was complicated by also having Lewy Body Dementia. The diagnosis changed his life irrevocably, and over the course of nine years he went from being a prominent surgeon to a frail old man as the diseases took their course.

As with most dementias, the deterioration in his cognition did not occur overnight. However despite this, small changes in his social circles began to evolve soon after his diagnosis. Whilst a solid few remained, many of his friends, including those from the medical community, stopped calling. Some made excuses but most simply faded away. Before long a similar pattern of desertion could be seen in my mother’s circle of friends as well as my own and those of my siblings, leaving us all with a feeling of isolation as the social supports we had so carefully constructed slowly eroded away. This sort of social stigmatisation and isolation are commonly reported by people affected by dementia, with many relationships waning despite cognitive faculties remaining largely intact. It remains hard to know whether the shift in friendships arose from my own issues in dealing with the diagnosis or whether my friends had lacked the knowledge of how to cope during this hard time. In reality it was probably a little of both. Fear, anger, shame, guilt and a general awkwardness tend to hang heavily over the heads of both those diagnosed with dementia and their carers in the early stages of the disease, as attempts are made to reconcile the diagnosis with their everyday lives.

‘People become very clever at being able to avoid you. It becomes a very lonely experience for many years.'

Carer

‘Once diagnosed, friends soon disappear; they find it hard to see the decline in your loved one, and then once they have died, the carer has to start and make a new life and sometimes [new] friends’

Carer [4]

In many ways, the early stages of dementia are the forgotten years. With only minor adjustments, diagnosed individuals are often able to retain a sense of normality in their daily lives. In his initial years with the disease, my father was able to continue enjoying the travel, films and friends in much the same way as he had prior to his diagnosis, albeit with a slight increase in help from those around him. He even acted as a member of the Consumer Advisory Committee for Alzheimer’s Australia (Western Australia) for over a year, passing on his insights on life after a dementia diagnosis. Despite this, I am ashamed to admit that a great deal of the stigma leveled at my father during this time emanated from me. In the early stages, it was easier to talk through him or not talk to him at all; to adjust to the loss that was to come rather than watching the disease slowly take its course. The heady mix of anger, guilt, shame and sorrow that his diagnosis had instilled in me resulted in my losing sight of who he was as a person, seeing instead the disease that would eventually claim his life. I lost a year to those wasted emotions. A year in which my father’s mind remained clear but in which my fear and shame kept him at arm’s length. In the end though it just took time; to adjust to the diagnosis and to realise that the time we could still share was more important than my own concerns.

As carers we are not immune to the stigma that continues to surround dementia and at times find ourselves perpetuating these notions rather than acting to halt them, particularly within those early stages. However, as time passes and our awareness grows, we are better able to see those affected by dementia as the individuals they are rather than the condition that afflicts them. Equally, it is imperative that we strive to challenge the stigma of dementia which pervades the wider community by ensuring that accurate representations of the condition are presented and an open discourse is established. Perhaps then the burden of dementia can in some small way begin to be reduced.

Sources

1. Alzheimer’s Society, Dementia: Out of the Shadows, 2008: London.
2. Alzheimer’s Disease International, World Alzheimer’s Report 2011, M. Prince, R. Bryce, and C. Ferri,
Editors. 2011.
3. Goffman, E., Stigma: Notes on the management of spoiled identity 1963, Englewood Cliffs, N.J.:
Prentice-Hall.
4. Alzheimer’s Australia NSW, Addressing the stigma associated with Dementia, 2010.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Sleepless surfing, cord-blood neurons, precognition and face-down dreaming

2012-09-24T22:26:00.001+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

NeoAcademic, Richard N. Landers, explores the link between a bad night's sleep and wasted hours on the web.
BrainBlogger, Katie Pratt talks cord-blood derived neurons.
Scott McGreal from Eye on Psych discusses the science behind precognition, but I guess you already knew that...
And Christian Jarrett explores that age-old question 'Does sleeping face-down induce more sexual dreams?'

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Animal mourning, cricket-fighting, school mentality and depressing donuts

2012-09-17T22:13:00.000+10:00

Here are my, mostly animal-based, medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

At The Scorpion and the Frog, Miss Behavior investigates how animals respond to their dead.
Decision making in Cricket-fighting (yes it's a thing) is put under the proverbial microscope at Neuroecology.
Scicurious' post dives into the benefits of herd, or school, mentality.
And Jennifer Gibson talks donuts and depression.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Religious preference, complimentary medicine, gender priming and more

2012-09-03T15:55:00.000+10:00

After a few weeks in the proverbial wilderness I return with a super-sized collection of medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Eric Horow, of peer-reviewed by my neurons, explores the question 'Do children learnt to hide religious preferences?'
Recent investigations into the prognosis of cancer patients using complimentary and alternative medicine were digested by both Respectful Insolence and Science-based medicine.
At Eye on Psych, Scott McGreal bravely asks 'could gender priming improve female recall of general knowledge?'

Vaughan Bell links to his recent Observer column on 'How stimulating dementia can help map our minds'. Technically a Observer article but well worth a read non the less.
And Neuroskeptic looks at 'your brain on Management'.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Inescapable Karma, Neuroscience and Race, and the Chemicals of Love

2012-08-06T23:09:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Dave Nussbaum discusses the inescapable nature of karma over at Random Assignment.
Neuroanthropology's Daniel Lende makes his first attempt at the dissecting the heady topic of 'Neuroscience and Race'.
And Yunhan Zhao's guest post, at The Scorpion and the Frog, takes a closer look at chemical underpinnings of that crazy little thing called love.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Brain size, footballers and anxiety

2012-07-30T23:05:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

The Cellular Scale asks 'Do small men think like big women?'.
Over at Brain Blogger, Amy Wong explores the risk of head injuries in footballers with a preference for heading the ball.
And Maria Konnikova's post on anxiety comes with a warning that it may cause, well, anxiety.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Fetal genomics, asexuality and medicinal marijuana

2012-07-18T11:43:00.001+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Neuroskeptic takes a glance into a not so distant future where fetal genome testing abounds, sparking some very interesting discussion.
Maria Panagiotidi of Nou Stuff takes a look at those of us who actually do prefer cake to sex in her post on asexuality.
And Natalie Jeanne Champagne's post at Psych Central offers a patient's perspective on medicinal marijuana.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Barbecue brushes, Big Food's balanced lifestyle and the invention of Karma

2012-07-09T20:46:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Maryn McKenna warns of the hidden dangers of that holiday barbecue.
Yoni Freedhoff's guest post at PLoS Blogs examines the role of Big Food in the 'balanced lifestyle' in 'Is obesity simply about a lack of "balance"? Why Big Food wants you to be fit'.
And Eric Horowitz of Peer-reviewed by my neurons asks the questions 'Why did we invent karma?'.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Llamas, cheetahs and posthmous diagnoses

2012-07-03T01:26:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

That's Basic Science explores the role that Llamas may play in the fight against HIV.
Gretchen Reynolds answers the age old question What can runners learn from cheetahs?
And Dr Jon Brock discusses the emerging industry of posthumous diagnoses with 'Did Alan Turing have Asperger syndrome?'

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Medically unique, the Worse-than-average Effect and the Black Death

2012-06-25T19:27:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Over at Chronic Health, Lutz Kraushaar asks the question 'Are you a unique medical case?'
Jeremy Dean discusses the 'flip-side to the Dunning-Kruger Effect' in his post on The worse-Than-Average Effect.
And Michelle Formanek guest-student-author at Aetiology posts on how the 'infamous "Black Death" still plagues the United States".

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Ineffectual exercise and autism in the water

2012-06-11T22:05:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

"Exercise doesn't help depression" turned out to be a stunningly poor summation of a recent article in the BMJ. Thankfully both Scicurious and Neurobonkers were on hand to set the record straight.
There must have been something in the water as similarly inaccurate headlines arose from a study investigating the effects of anti-depressants on autism genes. Enter a concise breakdown of the findings by Neuroskeptic and order was soon restored.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Chagas disease, veiled communication, cold-readings and soiled carpets

2012-06-05T01:46:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Maryn McKenna explores the near silent spread of Chagas disease.
Christian Jarrett investigates whether facial veils alter the communication of emotions.
Jordan Gaines talks of the neuro-side of psychics and clairvoyants at Gaines, on Brains (which crosses over into an impromptu interview).
And The Thoughtful Animal, Jason Goldman, asks whether a soiled carpet leaves our pets riddled with guilt.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Fast-paced risks, a son's potentially cancerous gift, the common sense of science and zombie ants

2012-05-28T16:22:00.002+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Jennifer Gibson takes a quick look at the risky business of our fast-paced lives.
Khalil Cassimally explores the link between a son's cells and a mother's cancer.
Dr Jon Brock delivers a beautiful review of Jacob Bronowski's The Common Sense of Science (which I now have on hold at the library and am very much looking forward to reading).
And over at The Cellular Scale. Zombie Ants. Enough said.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Know your neurons, a diff'rent look at kidneys and sympathy for psychopaths

2012-05-23T00:16:00.004+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Ferris Jabr reaquaints us with the familiar and at times not-so-familiar neuronal landscapes in a series of posts over at Scientific American entitled 'Know Your Neurons'. Part 1, Part 2 and Part 3.
Whizbang takes a Diff'rent Look at pedeatric kidney disease.
Mind Hacks' Vaughen Bell talks us through the logical holes created by an article on sympathy for pyschopathy and autism.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Cancer screening, 300ft falls and a how to on hiring

2012-05-08T10:11:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Henry Scowcroft clarifies the current state of blood tests for breast cancer risk at Cancer Research UK.
Steven Salzberg reports on surviving falls from great heights at Genomics, Evolution and Pseudoscience.
And NeoAcademic Richard Landers gives us an insight into the hiring practices of the future.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Smart drinks, neural robustness and Earworms

2012-04-30T23:26:00.005+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Jennifer Gibson, at BrainBlogger, gives us a smart excuse for another cold beer.
Wiring the Brain's Kevin Mitchell discusses 'Robustness and fragility in neural development'.
And Tom Stafford investigates the psychology behind those annoying earworms over at Mind Hacks. (Alright so this was originally posted at Future but it deserves a look for those who haven't already seen it.)

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Facial expressions, chronic stress and a stiff drink

2012-04-24T15:23:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Neuroskeptic assures us that facial expressions of emotion are still culturally universal.
Over at BodyinMind.org, Luke Parkitny discusses the dynamics of chronic stress and cancer formation.
And Dirk Hanson investigates why alcohol makes our minds wander in 'Dude, where's my metaconsciousness?'

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Social signals, stolen balls, ethnic group suffering and addiction on the streets

2012-04-16T16:28:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Miss Behavior investigates what happens when we send dishonest signals to those around us over at The Scorpion and the Frog.
Maya Kuehn discusses the intergroup dynamics of the Hunger Games with her Psych Your Mind post "Rue and Racism".
NeuroDojo's Zen Faulkes investigates the prisoners' dilemma and asks us whether we'd split or steal his Golden Balls.
And finally over at The White Noise, Cassie Rodenberg delivers a beautifully poignant post about the real faces of addiction.

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Olfaction, origins and autism

2012-04-10T11:28:00.000+10:00

Here are my medicine, neuroscience and psychology ScienceSeeker Editor's Selections for the week:

Emily Haines covers olfactory losses in Parkinson's Disease over at BrainBlogger.
Maria Konnikova explains our love of explanations in Hunter of Myths: Why Our Brains Love Origins.
And Kevin Mitchell explores de novo mutations in autism over at Wiring the Brain.

This post was written by Andrew Watt for A Hippo on Campus.

Are melatonin-laced drinks just taking the piss?

2012-04-04T11:28:00.003+10:00

At the end of a long day at work there's nothing quite like the salve of a glass of red to ease the troubles from your mind. Or perhaps a scotch is more your thing (neat or on the rocks I'm not here to judge). Then again maybe yours is a gin and tonic, an Old Fashioned or even just a cup of chamomile. The point is whatever your poison there are few among us who don't turn to a little liquid helper as the day draws to a close. Whether to dull those frayed nerves, to placate our worries, or let's face it to gently ease us into the calming refuge that is unconsciousness. Recently it appears however, that many of us are turning our backs on that hot toddy in favour of a hormonal liquer. Yep we're trading the merlot for the melatonin and the truth is we don't really know what it's doing to us.

Already widely available in the US, and slowly making their way to a store fridge near you, the relaxation drinks, with names such as IChill, Dreamwater and NeuroDrink, have recently found themselves the focus of a Nature Neuroscience Editorial, and for good reason. In the US the drinks, which contain ingredients such as melatonin, GABA and 5-HTP (a serotonin precursor), are classified as dietary supplements, meaning that they are not subject to the tests of safety or efficacy normally required for food and drugs. Rather as the editorial says 'It is instead assumed that the companies selling these products have conducted all of the necessary safety and efficacy testing before the products go to market (although there is no requirement that they release any information about such tests).' But before we dive into to a discussion of the safety of these products let's take a quick look at how consuming melatonin is thought to help us sleep at night.

Melatonin

Melatonin (or N-acetyl-5-methoxytryptamine for those of you playing at home) is a serotonin derivative produced by a small endocrine gland in the epithalamus, known as the pineal gland. First isolated back in the late 1950s, it was found to be intricately linked to circadian rhythms and, perhaps more importantly for our purposes, to sleep regulation. The synthesis of melatonin occurs mainly after dark when serotonin-N-acetyltransferase produces serotonin, from tryptophan, which is then converted to melatonin. This process also occurs during the day, however at a much slower rate as light signals at the retina are transmitted to the pineal gland, via the hypothalamus, resulting in a breakdown of serotonin-N-acetyltransferase and a subsequent reduction in its activity by approximately 100-fold. Or more simply about 100 times more melatonin is produced when it's dark outside than when it's bright.

So the pineal gland produces and accumulates melatonin before environmental and endogenous clues lead the gland to steadily release it from around 9.00pm. The melatonin release continues throughout those sleeping hours peaking between 2.00 and 4.00am, when our core temperature and state of alertness are at their lowest levels (or when we're fast asleep) before tapering off once the morning sun begins to peek around our bedroom curtains. But whilst it's generally accepted that melatonin helps make that pillow seem extra comfy it's not entirely sure how it all happens other than helping us sleep when it's dark and wake when it's light. But despite the gaps in our knowledge it's exactly this process that relaxation drinks are attempting to mimic. By introducing a high peak level dose of melatonin just before sleep, drinks such as Dreamwater attempt to kick start a solid night's sleep by telling our bodies they're already at those optimal stages of temperature and alertness and thus are ready for some serious shut-eye . But are they safe?

The simple answer is we don't know. One problem is that these products haven't been around long enough to know whether they are safe for short-term, let alone long-term use. The second issue is that negative effects resulting from the ingestion of such CNS targeting ingredients are notoriously hard to measure, especially when compared to the adverse effects in energy drink consumption. After all heart palpitations are much more readily observable than subtle changes in sleeping patterns, mood and cognition. These issues are further compounded by the fact that it is often a combination of these CNS targeting ingredients that are present in any one product, making it hard to delineate the individual effects of a single ingredient.

But whilst the FDA doesn't currently ensure the safety of these 'dietary supplements', it's interesting to note that they recently labelled melatonin-laced brownies as unsafe and warned manufacturers that the products could be seized from shelves if production continued. Like the relaxation drinks, the company producing the brownies had been marketing them as dietary supplements and stress relievers, however the FDA disagreed and issued a warning letter to the company stating that the cakes were 'adulterated' and contained 'an unsafe food additive' (more specifically melatonin). So what's the difference between the 'unsafe' melatonin in the brownies compared to the supplemental melatonin in NeuroDrinks? Nothing at all. As it would happen the difference all boils down to the fact that the drinks are not viewed as food under FDA guidelines. But this categorical oversight doesn't mean they should be given the green light. Especially when there are other more reliable, not to mention safer, sources of melatonin freely available.

Back in my day...

That's right, the concept of ingesting melatonin as a means of alleviating stress and restoring the wake-sleep cycle is by no means a novel phenomenon. In fact it is a traditional practice referenced in ancient Hindu and Yogic texts. Alright so obviously the tradition didn't involve popping down to the local store to pick up a bottle of IChill just before bed time, but it did involve drinking a ready supply of melatonin. But where would you get such a ready supply in those days of old? Well as it turned out the answer was inside us all along...

Known as 'Amaroli' (because urine therapy just didn't have the same ring to it), the practice involves collecting and drinking the mid-stream of your early morning evacuation. Taking care to avoid the initial and concluding flows that are thought to impart no health benefit whatsoever (and so just leave you with a bad taste in your mouth). Traditionally, Amaroli was performed in secret (a decision made after the early practioners encountered a number of awkward conversations...'Really you don't drink yours?') but thanks to modern technology Amaroli enthusiasts are now sharing their tips and tricks in open online forums. For example try adding some oregano it really helps with the taste, apparently (go on Google it you know you want to). Undoubtedly early Amaroli practitioners weren't aware that it was the soothing warmth of melatonin in their urine that was helping them drift right back to sleep, but the premise remains the same. Levels of melatonin in the urine are relatively high first thing in the morning and it is thought that the low pH of our gastric system is the perfect environment to convert our mid-stream melatonin back to its biologically active form. From there it is able to restore our circulating melatonin levels and thus ensure we continue to sleep like the proverbial log.

Now whilst it might be tempting to give these hormonal potions a go after a long day at work, when the thoughts of how tired you are are preventing you from sleeping. Why not stop and take a minute to consider just what it is that your potentially willing to risk for that good night's sleep. In my mind it's really not worth the hassle. After all do we really need another stressor to occupy our thoughts? So instead of that hormonal snake oil why not just take a moment to yourself. Take a deep breath. Have a cup of warm tea (or a glass of red) and try and enjoy those mid-stream dreams. But whatever you do, just don't forget the Oregano!

Sources

Bellapart J, & Boots R (2012). Potential use of melatonin in sleep and delirium in the critically ill. British journal of anaesthesia, 108 (4), 572-80 PMID: 22419624
Mills MH, & Faunce TA (1991). Melatonin supplementation from early morning auto-urine drinking. Medical hypotheses, 36 (3), 195-9 PMID: 1787809
Editorial (2012). Sip carefully. Nature neuroscience, 15 (4) PMID: 22449954

Images

Exhausted Salaryman by Hiromy
Pituitary and Pineal Glands

This post was written by Andrew Watt for A Hippo on Campus.

Editor's Selections: Choice, Coital conversations and Cleaning

2012-04-04T08:52:00.003+10:00

It is with great pleasure that I can announce that I am one of the newly minted Editors for ScienceSeeker.org (along with Sarah Chow, Cristy Gelling, Matthew Francis, Jason Goldman, Mark Hahnel, Peter Krautzberger and Allie Wilson). Each week I'll be selecting 3-4 of the best posts from across the blogosphere covering medicine, neuroscience and psychology for you all to enjoy. To get you all started here are my inaugral ScienceSeeker Editor's Selections:

Sam McNerney covers the paradox of choice over at Why We Reason? Are too many choices impairing our selections?
Tiffani Washington discusses why it's important to talk about what goes on behind your bedroom door behind your doctor's door in What We Don't Talk About When We Don't Talk About Sex.
And Christian Jarrett digests a study investigating whether that new carriage smell leads to more sanitary passengers at BPS Research Digest.

This post was written by Andrew Watt for A Hippo on Campus.

Removing epigenetic memory blockages in Alzheimer's disease

2012-03-01T21:34:00.000+11:00

The progressive deterioration of one’s social and cognitive functioning is often thought of as being synonymous with the normal aging process. After all we all forget names, misplace our keys and stumble over our words from time to time. Hell, sometimes it even happens in the absence of that second glass of wine. Yet you only need to look at Christopher Plummer's recent Oscar acceptance speech to realise that a deteriorating mind is not an inherent part of growing old. After all Plummer is 82 and appears to more on the ball than me most weekday mornings. Instead more often than not impairments to cognition in the elderly, and at times the not so elderly, are attributable to the presence of an underlying neurodegenerative dementia known as Alzheimer's disease. Whilst the causes leading to these impairments remain poorly understood, and largely contentious, new research published in Nature suggests that cognitive capacities in the deteriorating brain may arise due to 'epigenetic blockages in gene transcription', which, if the results are anything to go by, just might be reversible.

Some facts about dementia you'd probably rather forget

But before we sink our teeth into the recent study by Johannes Graff, let's take a moment to get some perspective on just how big a problem Alzheimer's really is. As most of you will already know, Alzheimer's disease (AD) is a highly varied and progressive disease accounting for up to 60% of dementia diagnoses worldwide (mostly in those over the age of 65). In fact it's estimated that five percent of people over the age of 65 will develop dementia, with the figure rising to 20% over the age of 80. However, that's not to say that those of us finding ourselves on the riper side of 65 are exempt from this insidious disease, as genetic forms of AD frequently strike people in their 50s, their 40s and occasionally even in their 30s. As of 2010, the number of people diagnosed with AD exceeded 35 million, bringing with them an annual cost of over $605 billion in care, treatment and lost productivity. That's right six hundred and five billion dollars! To put that in perspective the revenue of ExxonMobil, the highest ranking company in the world (with regard to revenue at least), is only $486 billion per annum and if we consider gross domestic product (GDP) then AD would rank at number 25, right above South Africa. And it doesn't stop there. The aging global population means that the prevalence of AD will increase dramatically, over the years to come. In fact it is expected to almost double every 20 years, reaching 65 million in 2030 and 115 million by 2050. This increase in prevalence will of course be accompanied by significant increases in the costs associated with the care and treatment of AD sufferers and highlights the need for more accurate and efficient diagnostic and therapeutic measures to be developed. And that's potentially why these new findings are so exciting.

I'll take my histones acetylated

In their study, Graff and co focused on the knowledge that our epigenetic processes help to orchestrate the stable changes in gene expression enabling memory formation. Of the modifications identified to date it is the acetylation of histones which is consistently associated with learning and memory, in such a way that histone acetylation is frequently reduced in animal models of neurodegeneration. If you're scratching your head at this stage wondering exactly what all this means then here's some basic background knowledge you mighht find useful. Histones are essentially protein spools which DNA wraps around to gain its structure and order. Without histones DNA would be an unruly mess akin to a dropped pot of spaghetti (if the pot had been full of only one really long piece of spaghetti). Acetylation on the other hand simply denotes introducing an acetyl group into a chemical compound, which in this case are the histones. Histone acetylation is important as it reduces 'the electrostatic affinity between neighbouring histones and DNA', thus allowing more space for the transcription of those all important memory-related genes. So histone acetylation means more readily transcribable genes, and conversely histone deacetylation means too much affinity between histones and DNA. To use the spool analogy again the DNA is wound to tight around the histones and thus a reduction in the ability to transcribe those memory genes is the result.

But what exactly is causing this reduction in histone acetylation in the AD-affected system? Well according to Graff it's all down to histone deacetylase (HDAC) levels, or more specifically a class I HDAC, known ironically as HDAC2 levels. Graff analysed the levels of HDAC2 in the neuronal tissue of two separate strains of AD transgenic mice (CK-p25 and 5XFAD for those of you playing at home) and found that HDAC2 levels were significantly elevated in the brain regions associated with neuronal degeneration (such as the prefrontal cortex and the CA1 area of the hippocampus, although curiously not in the CA3 area or the dentate gyrus). Interestingly, levels of HDAC2 in areas not affected by the neurodegeneration, such as the amygdala, remained normal and no differences in the structurally similar HDAC1 or HDAC3 were observed regardless of the brain region investigated.

Next the authors set out to ascertain whether HDAC2 was associating with genes in the mice hippocampi implicated in learning and memory, such as Homer1 and Cdk5, as well as genes involved in synaptic plasticity, such as Syp and Syt1. And not surprisingly it was! And yet it didn't seem to be associating more with housekeeping genes, such as β-actin, β-globulin or β-tubulin. In other words the tightening of the DNA around the histone spool led to a reduction in the transcription and subsequent expression of genes involved in memory and neural plasticity. Perhaps more excitingly though, was the finding that when the mouse CA1 hippocampal areas were injected with short-hairpin RNAs (obviously not actual hairpins just a means of knocking down genetic expression) to knock down the expression of HDAC2 they found that not only did itmanage to reduce HDAC2 levels to those indistinguishable from control animals but they also managed to alleviate the memory deficits associated with elevated HDAC2.

Of mice and men

Whilst promising these findings wouldn't be of much significance unless they could be tied back to the AD in humans. After all, unless specifically bred to do so, mice don't tend to make a habit of ending up with Alzheimer's related memory impairments. To do this the researchers analysed HDAC2 levels in the hippocampal CA1 tissue from 7 controls and 19 ADs. Like in the mouse tissue the researchers found that levels of HDAC2, but not HDAC1 or HDAC3, were elevated within AD brain tissue, suggesting that 'elevated levels of HDAC2 may also accompany cognitive decline' in the human brain.

But what is about the AD brain that leads to a buildup of HDAC2? Well like most features of AD it all comes back to β-amyloid (Aβ). That's right the researchers found that the pathological hallmark of AD, the peptide thought to be responsible for it all may also be responsible for the increases in HDAC2 observed in the study. This was determined by exposing primary hippocampal neurons to aggregated forms of Aβ, known as oligomers, with either the neurotoxic wild-type sequence (Aβ1-42) or the non-active reversed sequence (Aβ42-1). As expected this lead to increased levels of HDAC2 in the primary neurons exposed to wild-type oligomers but not the reverse sequenced ones. These results are perhaps best summarised by lead investigator Dr Li-Huei Tsai who said;

'We think beta-amyloid triggers a cascade of damaging reactions. One of these is to activate HDAC2, which in turn blocks the expression of genes needed for brain plasticity. Once this blockade is in place, it may have a more systemic, chronic effect on the brain.'

So where does it all lead from here? Well not surprisingly the authors of the study are currently working on identifying HDAC2-specific inhibitors to use in further drug development, a far cry from the Aβ-centric agents currently under investigation. However even if they are successful it is unlikely that such a drug will be the silver bullet the AD field is hoping for, as despite the fact that reducing HDAC2 appears to restore cognition it doesn't actually appear to stop neuronal death. Instead it is thought that HDAC2 reduction acts to enhance the neuroplasticity of the neurons which remain, strengthening their ability to connect and communicate with those around them. Either way, we'll more than likely find out just how effective an HDAC2-inhibitor can really be in the years to come (or the decades to come if you know your drug development) and in the meantime we get to be amazed by the new research that will no doubt be spurred on by these results. After all it was only a few days ago that the functionality of damaged neurons in the AD brain were thought to be irrevocably lost, but today. Well today there's just that little bit of hope.

Sources

Gräff, J., Rei, D., Guan, J., Wang, W., Seo, J., Hennig, K., Nieland, T., Fass, D., Kao, P., Kahn, M., Su, S., Samiei, A., Joseph, N., Haggarty, S., Delalle, I., & Tsai, L. (2012). An epigenetic blockade of cognitive functions in the neurodegenerating brain Nature DOI: 10.1038/nature10849
Karran E, Mercken M, & De Strooper B (2011). The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nature reviews. Drug discovery, 10 (9), 698-712 PMID: 21852788

Images

'Old man' by Martinhampl

'Complete histone with DNA' by Zephyris

This post was written by Andrew Watt for A Hippo on Campus.