Visible neuroscience

Imaging techniques enable neuroscientists to learn about the structure and function of cells in the nervous system. Here, Dr Zoltán Rusznák shares some captivating images of the brain and how they were made.

Neurons are the building block cells of the brain and spinal cord, communicating with each other through synapses to regulate nervous system function. Relating the shape, size, and location of neurons to their function is important in understanding mechanisms in brain health and disease. However, because neurons are small, three-dimensional, and embedded among many other cells in the nervous system, special techniques are required to be able to see them. The following pictures show neurons in the cochlear nucleus, which is the part of the brain that decodes sound information from the ear.

Stacking up to localise sound

Globular bushy cells illuminated by a fluorescent stain

Globular bushy cells illuminated by a fluorescent stain

What’s in this picture? Globular bushy cells are neurons in the cochlear nucleus that act as sophisticated timing devices. They measure tiny delays in how quickly a sound reaches both ears, which is the basis of how we localise the source of a sound.

How was it made? The picture on the left was taken with a camera attached to a microscope. It shows a round bushy cell body in the middle of a single, very thin slice of brain tissue – a slice only 0.06% of the thickness of a grain of salt! The right-hand picture is a stack of 40 images taken from successive slices of the same piece of brain tissue – imagine a stack of salami coming out of a deli slicer. The image stack results in a view of much greater depth, so that a second bushy cell body becomes visible, as well as a detailed view of the synaptic nerve terminals, indicated by the several bright green structures on the cell bodies.

Putting the puzzle together

Giant neurons illuminated by a fluorescent stain

Giant neurons illuminated by a fluorescent stain

What’s in this picture? ‘Giant neurons’ of the cochlear nucleus receive sound information from the ear and help to localise the source of sound from a single ear.

How was it made? These pictures are also made from stacks of single images, like in the previous picture. However, since the giant neurons are so, well, giant, many adjacent image stacks have to be assembled like a puzzle in order to capture the many branching nerve endings. Each square in the pictures corresponds to a single field of view of the microscope.

Merging muscarinic receptors

Granule cells and muscarinic receptors illuminated by fluorescent stains

Granule cells and muscarinic receptors illuminated by fluorescent stains

What’s in this picture? These small round neurons in the cochlear nucleus are called granule cells. Neurons have proteins on their surface called receptors that respond to chemical messengers and transmit signals throughout the neuron. Sometimes we want to know the specific type and location of receptors that a messenger binds to in order to transmit its signal.

How was the picture made? Different fluorescent dyes are used to distinguish the receptor from the rest of the neuron. The left-most image shows green, bead-like dots that indicate the presence of a particular type of receptor called a muscarinic M3 receptor in a slice of brain tissue. The middle picture is taken from the very same piece of brain tissue, but the tissue is instead stained blue to define the nucleus of the granule cells. When the green and blue images are merged (right-hand picture), the green dots are showed to be surrounding the blue cell nuclei. This tells us that the receptors are located on the surface of the granule cells, and suggests that these receptors mediate the effects of certain neurochemical messengers in the cochlear nucleus. This information is helpful to determine how hearing works and what might go wrong in auditory disorders.

A ride for my Dad

NeuRA volunteer Lizzi Mallett explains why she decided to participate in the Memory Cycle to Cambodia in March 2015 and why fundraising for NeuRA’s research is so important to her.

Six years ago my family and I said goodbye to my dad, John Mallett, as he slipped away from our world after suffering from the rapidly progressing motor neurone disease (MND) and frontotemporal dementia for five short years. His battle with these awful diseases started when I was 15 and he was only 58. He lived life each day as if it was his last. His thirst for life took us on a wild journey and he loved every second of it. It is because of my dad that I have decided to dedicate my life to supporting and helping NeuRA. At the beginning of the year I moved to Sydney from Perth and began volunteering with NeuRA’s Foundation team.

When the opportunity for the Memory Cycle came up, I thought that there was no way someone like me, who doesn’t cycle regularly, could do a challenge like this. We would be cycling from Vietnam to Cambodia, and I would have to fundraise a minimum of $3,500 while living on the other side of the country from my entire support network. However, my mother reminded me of my dad’s determination in life and how he purchased a bike when he was ill but could not ride it. He taught me that if I put my mind to something, that I could achieve anything! And by *anything*, I mean the time he sneakily planned a trip from Perth to Hampton Island all on his own when he had already lost the ability to speak and swallow – however, that’s a story for another time. With this determination in mind, I thought, ‘yes, I can do this, I’ll cycle for my dad’. After all, Dad was the one who taught me how to ride a bike and we used to do everything together. This is something he would like to have done and if he was still here with us today, I’m sure he would have signed up for the challenge too. So I signed up and started my fundraising page. Almost instantly, thanks to social media, I raised $1,000 in under a week. Whoa!! Who knew I could do that. I am extremely close to reaching my minimum fundraising goal. See, my dad was right! The mind works wonders; you can achieve anything when you put your mind to it. The Memory Cycle is the best way to fundraise for NeuRA as I get to travel, meet new people, do really cool things with the Inspired Adventurers, and work out, all at the same time.

I had an unbelievably close bond with my dad and it breaks my heart seeing people suffering from neurological diseases just like he did. If you have a desire to help NeuRA and make a difference to so many families suffering from the illnesses that NeuRA researches, then please donate or sign up for Memory Cycle and ride in Cambodia with me. We will have an absolute ball! If you would like to contribute and cannot join the cycle team (even though you really want to!) then you are more than welcome to give a little donation on my fundraising page, and follow my journey on my blog.

I hope to see your pretty little faces on NeuRA’s Memory Cycle team; otherwise, we appreciate every little cent that comes our way. NeuRA is making a huge difference to so many people’s lives, including my own family. Your donation will help NeuRA conquer neurological disease one step at a time.

Dad and I

Dad and I


Dementia: when do I know I have a problem, and what is happening in my brain?

Dr James Burrell is a Senior Research Officer and clinical neurologist whose research interests lie in linking clinical symptoms and pathology in dementia syndromes.

Dr James Burrell

Dr James Burrell

In my work as a clinical neurologist, I often encounter people who are concerned that they might be developing the dreaded d-word: dementia. They report being more forgetful than previously, forgetting the names of people, places or things, or perhaps just not feeling as ‘sharp’ as they once did. In my experience, these sorts of concerns are common. Importantly, however, only a proportion of people with such symptoms actually go on to develop dementia.

Working out who will develop dementia, and more specifically which type of dementia will be developed, is one of the major challenges cognitive researchers and clinicians face. We are presented with two separate, but related problems: first, how can we tell when minor forgetfulness heralds the onset of something more serious? Secondly, if someone has an obvious dementia, how can we make an early and accurate molecular diagnosis?

We know from many well-designed studies that neurodegenerative disorders begin years before any symptoms develop, and that to be effective a treatment will most likely need to start at the very earliest stages, before any significant and permanent damage develops. On the other hand, not everyone with mild cognitive symptoms actually progresses to develop dementia. Being able to accurately identify patients at risk of developing dementia at a very early stage is one of the major goals of research in neurodegenerative diseases.

In the Frontier clinic based here at NeuRA, we are often faced with the opposite problem: we assess patients with early dementia who present with memory, language, or behavioural disturbances, but it can be difficult to work out the specific underlying brain disease. In many ways, our research aims to bridge this gap between the problems related to ageing that people face in their everyday lives and the physical changes in the brain that are ultimately responsible. We use a combination of methods, including detailed clinical assessment, neuropsychological or cognitive testing, sophisticated brain imaging, neurophysiological techniques, gene testing, and even blood and tissue biomarkers, to try and better link cognitive symptoms and specific brain diseases. With collaborators in the UK we have even developed a new app, for cognitive testing in clinical practice (ACEmobile™ for iPad, available from the Apple App Store). Only after we can make an early and accurate diagnosis of a neurodegenerative brain disorder will the hunt for a meaningful treatment really forge ahead.

Contracture: understanding mechanisms and testing treatments

As part of a new National Health and Medical Research Council Program Grant on motor impairment, Prof Rob Herbert aims to advance the transfer of new understanding of physiology and pathophysiology in motor impairment toward the clinical outcome of improved motor function.

Prof Rob Herbert

Prof Rob Herbert

Motor impairment is a common consequence of a number of illnesses and injuries. One type of motor impairment that is an important cause of physical disability is muscle contracture. A contracture is a stiffening of the muscles that limits normal joint movement, and severe contractures cause deformities that are the most visible manifestation of brain damage. Contractures arise when brain lesions, including those that arise from stroke or traumatic brain injury, cause paralysis or spasticity. Paralysis and spasticity change the mechanical environment of muscles – that is, they cause muscles to experience different patterns of activity, different changes in length and different forces than would normally be experienced. The muscles adapt in response to their altered mechanical environment by becoming stiffer, causing joints to become less mobile.

Contracture is a common problem. In a recent study, my colleagues and I monitored 200 consecutive people admitted to a Sydney hospital with the diagnosis of stroke. Six months after admission, half of all those people had developed at least one contracture. Contractures are also common in people with many other sorts of brain lesions. For example, contractures are prevalent in people who have had a traumatic brain injury, or who have multiple sclerosis or cerebral palsy.

Contractures prevent joint movement, so they cause physical disability. For example, many people who have had a stroke or traumatic brain injury develop contractures of the calf muscles. Calf muscle contractures impede ankle motion, making it difficult to stand up from a chair or walk normally. In the same way, contractures of shoulder muscles can impair the ability to reach and contractures of wrist and finger muscles can impair grasp. Severe muscle contractures can cause the limb to adopt a fixed position. For many people, contractures become a much greater impediment to normal movement than the paralysis or spasticity that initially caused the contracture to develop.

There has been surprisingly little research into the mechanisms of contracture. As a result, the mechanisms are poorly understood. Studies on animals have shown that it is possible to make muscles become short or stiff with a number of experimental procedures. For example, leg muscles can be made short by immobilising the leg in a plaster cast, and diaphragm muscles can be made short by inducing emphysema (a lung disease). These studies show that the stiffening of muscles can occur either because of changes in the muscle tissue (the muscle “fibres” or “fascicles”), or because of changes in the tendons that join muscle fascicles to bones. But studies on animal muscles can’t tell us about the mechanisms of contractures seen in human populations. Surprisingly, it is still not clear whether contractures in people who have had a stroke or traumatic brain injury are due to changes in the muscle fascicles or tendons.

There is just as much uncertainty about how to prevent and treat contracture. For the last half-century, physiotherapists and nurses have applied stretches to muscles, or passively moved limbs, or applied splints or casts to stretch the limb, with the aim of preventing or treating contractures. But recent research suggests these interventions have little effect. For example, in one study, 63 volunteers who had experienced a stroke were randomly allocated to receive either a wrist splint or no splint. Two months later there was no discernable difference in the stiffness of the wrist of people who had or had not been splinted. There have now been over 35 studies like these, and they quite consistently show little or no effect of stretch or movement-based interventions. For now at least, there are no treatments that have been clearly shown to prevent or reverse contracture.

Eventually, scientific research will provide answers, both about the mechanisms of contracture, and about how to prevent and treat contracture. The first steps have been made in identifying the abnormalities of gene expression that are ultimately expressed as contracture. New ideas for treatments are being generated by basic research, for subsequent testing in clinical trials. Our motor impairment program will study human volunteers and patients to learn more about normal motor function and the mechanisms of motor impairment, and to test the clinical efficacy and mechanisms of novel treatment interventions. The development of new techniques for imaging and measuring the internal architecture of muscles using MRI provides one promising advance. One study will look at how muscle tendons and fascicles are recruited during movement, which will inform subsequent clinical studies in people in whom contracture is common, such as people with stroke, spinal cord injury and multiple sclerosis.

Hopefully, the next decade will see major advances in both our understanding of the mechanisms of contracture and how to treat them.

An example of one of the unique muscle images generated by Prof Herbert's team. In the centre is a human leg muscle. The blue lines show the course of muscle cells in six locations in the muscle. The insets provide information about how the cells terminate on the tendinous sheets that cover the upper and lower surfaces of the muscle.

An example of one of the unique muscle images generated by Prof Herbert’s team. In the centre is a human leg muscle. The blue lines show the course of muscle cells in six locations in the muscle. The insets provide information about how the cells terminate on the tendinous sheets that cover the upper and lower surfaces of the muscle.

An international approach to tackling Parkinson’s disease

Dr Nic Dzamko and Prof Glenda Halliday have put together an international team dedicated to researching the causes of Parkinson’s disease. They will be the first in the world to use valuable early clinical samples to identify the genetic and molecular underpinnings of this brain illness.

Parkinson’s disease is a debilitating neurodegenerative disorder with no current cure. 1 in every 30 Australians is diagnosed with Parkinson’s disease, and these numbers are predicted to rise. Over the last 10-15 years, it has emerged that genes play an important role in the risk of developing Parkinson’s disease. Approximately 16 genes have now been identified that increase the risk of developing Parkinson’s disease. Understanding what these genes do in the healthy brain, and how their functionality might go wrong, has become a major focus in the search for clues about the cause of this disease.


Dr Nic Dzamko in the laboratory

One of these genes, called LRRK2, has received considerable attention. The LRRK2 gene encodes a protein that belongs to a class of enzymes called kinases, which is interesting to researchers because many anti-cancer drugs developed by the pharmaceutical industry also act by blocking kinases. In the past few years, more than 20 drugs that can block the kinase LRRK2 have been patented. While it is hoped that these drugs may be beneficial for the treatment of Parkinson’s disease, more work needs to be done to understand exactly what LRRK2 does, and therefore whether drugs that block its action will be safe and therapeutically useful. To better understand the function of LRRK2, our team at NeuRA has initiated two new projects in collaboration with scientists from around the world.

The first project involves us leading a group of scientists from London, Tokyo, California and the Netherlands. Using 400 samples that have been sent to us from these locations, and that cover a range of brain regions at different disease stages, we will determine if, when and where the expression of the LRRK2 enzyme goes wrong in the Parkinson’s brain.

The second project aims to investigate the idea that inflammation is linked with Parkinson’s disease, in collaboration with researchers in the US and Europe. This project is particularly exciting, as it may identify much-needed markers of early disease. By working with the worldwide LRRK2 Cohort Consortium, established by the Michael J Fox Foundation for Parkinson’s Research, we have access to more and better samples to ultimately obtain more meaningful data. We will measure a range of biological markers associated with inflammation in serum and cerebrospinal fluid. By comparing the extent and type of inflammation in people who do and do not have certain genetic mutations, and between people with Parkinson’s disease and healthy controls, we will identify whether inflammation is an early sign of Parkinson’s disease. This world-first access to blood samples from people with a large genetic risk of getting Parkinson’s, but who do not yet have the disease symptoms, is a chance to try and identify potential treatments for the early stages of this illness.

These projects have taken about a year and over 300 emails to come together. Although meetings are often scheduled in the very early hours of the morning to accommodate time zones, working together as an international team to leverage skills and resources is an important step toward solving the problem of Parkinson’s disease. Of course, our work would not be possible without the funding we have received for these projects from the Michael J Fox Foundation and the Shake it Up Australia Foundation.

Reasons to run

This Sunday, August 10, the Sydney City2Surf will include two groups of people who have more reasons than many to get up early and run to Bondi beach.

Evan Brownsmith is organising a team of eager accountants from PKF Lawler Tamworth and Walcha, NSW to run the City2Surf in support of motor neurone disease (MND) research.

PKF team cropped

The PKF Lawler team: (L – R) Blair Richards, Kelee Hawker, Evan Brownsmith, Michelle Higgerson and Nicole Parkinson

This terrible disease has recently been diagnosed in two of PKF Lawler’s longstanding clients, with a profound impact upon their families and friends and the whole team at PKF Lawler. Through our efforts, both running and fundraising, we hope to raise awareness in the Tamworth community of the impact of MND. By partnering with NeuRA we hope to provide valuable funds for the development of life-altering treatments for MND sufferers.

Like most people, I have a love-hate relationship with running. On a good day – when there is sun and very little wind, and it’s not too hot and not too cold, and you’re feeling fit and your legs feel strong, and you’re wearing the right outfit, and the scenery is good, and no-one is watching you, and you’ve got a really good album playing in your ears – running is the best thing in the world! There’s nothing better than the sense of achievement you get from pushing yourself further as your feet pound the pavement. On every other day, running sucks!!

Most of the time, running is really hard! That’s why we come up with so many excuses for not doing it. We like the idea of running, but often we don’t enjoy running itself. What we don’t think about each time we choose not to run, though, is how lucky we are to be able to run. Most sufferers of MND will lose the ability to run. This is the inspiration for team PKF Lawler in the City2Surf, and this is what motivates me to get off the couch, put my joggers on and make the most of my good health and good fortune.

For those who don’t know, MND is the name given to a group of diseases in which the motor nerve cells (neurons) controlling the muscles that enable us to move, speak, breathe and swallow, undergo degeneration and die. Motor function is controlled by the upper motor neurons in the brain that descend to the spinal cord; these neurons activate lower motor neurons, which exit the spinal cord and directly activate muscles. With no motor neurons to activate them, muscles gradually weaken and waste away. These effects are irreversible, and as MND sufferers progressively lose function, their quality of life is diminished and independence is undermined.

On August 10 this year my colleagues and I hope to make a significant difference for these people. We cannot directly improve the lives of MND sufferers, nor can we make it easier on their families. We cannot hope to cure this terrible disease ourselves, but we know that our modest contribution to NeuRA will help the very people who just might. Perhaps more importantly, through demonstrating a willingness to ‘give it a go’, we are setting a great example to the community of Tamworth. We want to show that it’s important to get out there and have a crack, not because we should, but because we still can.

Fundraising stall

Ashlee Schwennesen and Julianne McDougall raising funds with a fresh produce stall

You can donate to the PKF Lawler team here.


Simone Riley is participating in the City2Surf with her family to support stroke rehabilitation research and to honour her Dad, a proud City2Surfer.

dad and me

On July 21, 2013, my Dad, a man who lived a healthy, active, and happy lifestyle, was stopped in his tracks by unfortunate genetics and a nasty stroke.

A man who was 64 years young, who had run 20+ City2Surfs (his favourite event) and over 60 marathons, trekked in Nepal and to the top of Mt Kilimanjaro, and was training for a trek from France to Spain, Dad was now in for the biggest challenge yet. His was an atypical stroke, meaning that he didn’t suffer the ‘usual’ deficits in movement that stroke often inflicts, but he did lose his vision and began to experience major cognitive and memory deficiencies.

Simone’s dad in Nepal

As Dad’s hospital days turned into weeks, and then months, our hope went up and down like the rollercoaster going on in Dad’s head. On my first visit to the hospital, I walked into a dark room and was faced with a body on a mattress on the floor that was heavily sedated, as the hospital staff didn’t know what else to do! When Dad woke up every now and then, to walk and eat, our hearts broke when he didn’t recognise me, or even my Mum, his wife of 43 years! Thankfully, we found a Brisbane doctor who agreed to come to the Gold Coast to assess him. This was the first hope we had. After moving hospitals, adjusting his medication, and some wonderful rehabilitation, physiotherapy, and speech therapy, we gradually saw the man who ‘once was’ slowly coming back. He once again knew who Mum was, who I was, and also recognised his other daughters, his son, his grandkids, and other people important to him. After almost six months in hospital, my dad walked out with my mum and went home.

The start of his (and her) new lives involved major adjustments; Mum was now his full time carer and also unfortunately had to take on the role of rehabilitator. I felt compelled to do and find what I could to help them with the struggle to find appropriate post-hospital rehabilitation.

While researching stroke, I stumbled across NeuRA. What better way to honour my Dad than to join the NeuRA City2Surf team and make him proud; to run his favourite event, while raising much-needed funds for a charity that will continue research into stroke rehabilitation and one day perhaps even prevent stroke altogether?

It has almost been a year since Dad’s stroke. Things are far from perfect; he has good days and bad days. Only last week, when I sat holding his hand on the couch, he knew I was there, but couldn’t, for all his wanting and trying, get my name out. His vision will never come back, but through trial and error and ups and downs he is rising, admirably, to his challenges.

pb marathon

This year, along with my sister, my best friend (who is like Dad’s fourth daughter), my Mum, some cousins and lots of Dad’s friends, Dad will once again take the trip to Sydney to run/walk/shuffle/crawl/hop/skip/jump; in short, do whatever it takes to complete his annual City2Surf! Given that Dad really doesn’t like the fact that he missed it last year, participating in this year’s race is in itself an achievement that we will all enjoy, almost as much as the cold beer we share with him at the finish line.

You can donate to Simone’s fundraising effort here.

You can also donate to the 2014 NeuRA Runners team here.

The life of an early career researcher

An early career researcher is an interesting creature – focussed, driven and often self-critical. Outgoing Chair of the Early Career Committee (ECC) at NeuRA, Kirsten Coupland, explains what it is like being a young scientist and the role the committee plays in supporting careers.

Early career researchers are those working in science who have completed their PhD less than six years previously or who are under the age of 40; whether studying or employed, involved in academia, or industry. There are around 120 early career researchers currently at NeuRA but this number fluctuates as people take exciting steps in their careers. These researchers are just discovering what a career in research entails. They are finding that a scientific career is not as structured as one in the corporate world; skills are learnt on the job and successful outcomes to experiments often initially elude them. Young researchers learn at the deep end. The work of the ECC, of which I am the outgoing Chair, is important for young researchers at NeuRA. We provide events and seminars that develop the skills and professional attributes young researchers need to cultivate a successful career in science.

What it takes to be a scientist

The world of research is extremely competitive and many of the things that set one scientist apart from the crowd are less tangible than research results. Being a good scientist requires the ability to communicate, have a strong network, a comprehensive knowledge base and confidence.


Kirsten Coupland in the laboratory

What we do 

NeuRA’s ECC aims to give young researchers the ability to cultivate these assets and enjoy themselves at the same time. Events the ECC orchestrates encourage young researchers to interact with new people from different research groups. In doing so, they not only become confident at communicating their research to scientists from other fields, but they also start developing a network they will use throughout their career. Initiatives include regular seminars featuring speakers from around the country who discuss topics such as ethics, social media, and where to source funding.

Panel discussions of post-docs or non-academic science careers have helped get early career researchers thinking about what they will do with their scientific knowledge. Informal coffee meet-ups allow students to discuss their research with a mixed audience and interact with people they may not know at NeuRA. Early career researchers are the future generation of scientific research. It is important they have the skills and attributes necessary to carry out creative and exciting science that will revolutionise the way we understand the human body.    

Providing for the future

Why is it that Australians prepare fiscally for retirement, but do not routinely donate to research into diseases of brain and mind, which will affect many Australians during their retirement?

DSC_3155Many people begin to take an active interest in preparations for retirement at some point during their adult life. Obligatory employer contributions make it possible to begin superannuation savings early in working life, and additional voluntary contributions are incentivised by tax benefits. Many people feel a sense of pride in this financially prudent approach to the future, and are able, at the end of a productive working life, to approach retirement with a safety net or a cushion; in short, some degree of financial security that will provide necessities as we age.

Ageing, however, cannot be dissociated from rising health costs and an unknown degree of necessity to rely on others to cope. There are more complex factors in how we allocate our financial resources when approaching older age that need to be taken into consideration.

There is a conundrum here: people make provision for an active, healthy and fulfilling retirement; however, they often do not consider donating to research and development in areas of health that are relevant to ageing populations. Many donors to biomedical research may be drawn to illnesses more prevalent in younger people, such as childhood cancer or breast cancer. Nevertheless, there remains a brutal reality for older Australians, who face the prevalence of dementia as a major barrier to health and quality of life. More than 320,000 Australians are currently diagnosed with this illness, and this figure is set to rise to 900,000 by 2050. There is currently no cure for dementia or for many other types of neurodegenerative disorders that also affect an ageing population, such as Parkinson’s disease and multiple systems atrophy.

So, when we are in a position in life to contribute to research, why don’t we choose to prioritise donations to research into neurodegenerative conditions, which incur significant costs and will affect an increasingly large proportion of the population?

Perhaps this asymmetry in choice is brought about by fear. Neuroscience research has enabled an increased understanding among the public of the effect of genes on heritable disorders. On the flipside, though, being able to predict one’s own vulnerability to diseases of the brain and mind may be only a grim reminder of a difficult future. Perhaps it is more comfortable for people to suppress this pessimistic prospect by contributing to research programs in which the afflicted individuals are youthful, the organ replaceable or the condition reversible. This allows the donors, who may often be facing middle age or older, to distance themselves from the fear that comes with increased awareness of their own vulnerability and to feel that they are making an effective difference through supporting translational research.

It is crucial that we bridge this apparent divide. Greater knowledge of the causes of neurodegenerative illnesses, and a more productive search for cures, can have positive feedback. In short, successful research often begets greater funding.

As demands on carers and aged care institutions become more apparent with the sheer numbers of Australians increasingly burdened with neurological diseases, the public will demand a collective reassessment of priorities in research funding from government and philanthropic sectors. The challenge will be to grow the pool of available funds, without diverting them from other areas of priority. Perhaps this challenge is something to consider during financial planning for retirement.


Cannabidiol – a glimmer of hope for Alzheimer’s disease?

Alzheimer’s disease is the most common form of dementia, which affects around 330,000 Australians. In 2009 – 2010, the healthcare cost of dementia was over 4.9 billion dollars in Australia. Both of these figures are on the rise, given that our life expectancy is increasing.

People living with Alzheimer’s disease experience a range of symptoms that include social withdrawal and problems with remembering places, objects and people, and these symptoms become progressively worse with time. In the brain, aside from the increasingly well-recognised amyloid plaques and tangles, imaging and post-mortem analyses have also found extensive neuronal degeneration, inflammation, toxicity and oxidative stress, and these processes are likely to contribute to the development of Alzheimer’s disease.

Current treatments are unable to stop the disease progression, and the quest to find a viable treatment for Alzheimer’s disease continues. Many treatments have been designed to target single brain systems that are affected in Alzheimer’s disease. However, this approach is not sufficient for two reasons: 1) more than just one system is affected in the disease, and 2) it may be too late to administer these treatments once the disease has been diagnosed. Research now suggests it may be more beneficial for patients if treatments targeted a range of systems that are altered in Alzheimer’s disease and could be administered early, perhaps even before disease symptoms are prominent, as a method of prevention.

So where does one find a treatment that can exert neuroprotective, anti-oxidant and anti-inflammatory effects all at once? Well, the answer might lie in a compound known as cannabidiol. Cannabidiol has been shown to have all the above properties, which could be relevant for Alzheimer’s disease. However, there have been only a few studies that have followed up on this link, perhaps because many people might be eager to dismiss cannabidiol as a treatment due to concerns that it may exhibit the psychoactive properties of other compounds obtained from the cannabis plant. But in fact, cannabidiol is behaviourally inactive in humans when taken over long periods of time, including in people with schizophrenia and Huntington’s disease. Cannabidiol also prevents the memory-impairing effects of THC, the main psychoactive compound of cannabis. And, in promising news for Alzheimer’s research, cannabidiol has also been shown to reduce amyloid production and increase neurogenesis in brain cells. With this in mind, it is only logical that cannabidiol should be tested for its potential to benefit those with Alzheimer’s disease, as it might counter some of the main biological changes that are occurring.

David Cheng has just completed his PhD at NeuRA under the supervision of Dr Tim Karl.

David Cheng has just completed his PhD at NeuRA under the supervision of Dr Tim Karl.

My study, published in the journal Psychopharmacology, was the first to investigate the effect of cannabidiol treatment in a transgenic mouse model of Alzheimer’s disease. This mouse model carries two genetic mutations that are associated with familial Alzheimer’s disease, and the mice show behaviours that are relevant to Alzheimer’s symptoms, such as social recognition and spatial memory deficits. Since normal mice have a tendency to explore either new things or other mice, we compared how well transgenic mice fared in a test called the social preference test, which measures the amount of time that the test mouse spends exploring either a familiar or a new (never before seen) mouse. I discovered that the Alzheimer’s model mice spent the same amount of time exploring both the new and familiar mice, showing that they were unable to tell the difference between the two. Excitingly, daily cannabidiol treatment given over 3 weeks restored the social recognition memory of the transgenic mice.

In a separate study, soon to be published in the Journal of Alzheimer’s disease, cannabidiol was given to the transgenic mice every day, beginning at a very early age, to test whether it can be administered early as a prevention against the social recognition memory deficits. Promisingly, the development of recognition deficits in the disease model mice was prevented by the cannabidiol treatment. Using various biochemical techniques, I also found evidence to suggest that this effect might be mediated by the anti-inflammatory properties of cannabidiol.

These findings are extremely interesting as they show cannabidiol might have behavioural and biological effects that could benefit people with Alzheimer’s disease. Of course, we know that mice are not exactly like humans, but mouse models give researchers a great amount of insight into the effects of Alzheimer’s disease genetic mutations on both behaviour and biology. For example, links can be drawn between the social recognition deficits displayed by the Alzheimer’s disease model mice and the inability to recognise familiar faces in people with Alzheimer’s disease. Imagine what it would mean for people with Alzheimer’s disease and their friends and relatives if they could still recognise their loved ones! With more research, it will be possible to gain a better understanding of the exact mechanisms behind the beneficial effect that cannabidiol has already shown in this mouse model, paving the way for possible clinical trials in the future.