Brain detectives: 10 amazing Kiwi insights

Sunday Sep 4, 2016

The human brain is one of the most complex systems ever known. Photo / Getty Images

At some point in their life, one in five Kiwis will suffer a neurological disorder - and rates are expected to spiral as our population ages.

That's unless scientists can find new ways to cure or treat conditions such as Alzheimer's and Parkinson's diseases, by unravelling one of the most complex systems ever known: the human brain.

As investigators share their latest breakthroughs at Brain Research New Zealand's annual conference, science reporter Jamie Morton takes a look at 10 new Kiwi-led advances.

1. Solving the mystery of Huntington's Disease

It's called the globus pallidus - and it could be the key to new treatments or a cure for Huntington's disease.

In a new study, Auckland University researchers focused on the specific part of the brain involved in helping us carry out movements.

Movement issues are one of the most common symptoms of the cruel genetic disease, which is characterised by excessive uncontrolled motions called "chorea" and eventual immobility.

Comparing the tissue of Huntington's-affected brains with that of normal tissue, the team looked at how degeneration in the globus pallidus was related to symptoms before death.

They discovered the damage seen in some portions of the region were associated with cognitive problems and all motor impairments - except for chorea.

"This research tells us that in order to deal with the motor and cognitive issues of Huntington's disease we need to repair both of these areas," study leader Dr Malvindar Singh-Bains says.

Because different symptoms were attributable to damage in different areas, the key to curing the disease would not simply be fixing the damage in a single area, she says.

There remained no cure or treatment for the disease, which affects about one in 10,000 people worldwide.

"We desperately need a way to halt the progression of Huntington's disease and one of the ways we can be sure that dream cure will actually work is to know how the disease affects the brain.

"This research puts us one step closer to new treatments or a cure."

2. Painting a picture of Alzheimer's disease

Auckland University researcher Lakshini Mendis.

In Alzheimer's disease, cells in the part of the brain that control memory and learning, called the hippocampus, slowly start dying.

Yet researchers still don't really know why these certain cells are targeted.

Searching for an answer, Auckland University researcher Lakshini Mendis and Associate Professor Maurice Curtis and Professor Richard Faull turned to lipids, which envelope the cell machinery and serve as the basic building blocks of living cells.

To compare differences in lipids in Alzheimer's and normal brain tissue, they drew on a relatively new imaging technique that allowed them to see exactly where in the hippocampus these different lipids were distributed.

"It enabled us to find out which regions of the brain affected by Alzheimer's disease were high in particular categories of lipids and in which regions they were low," Curtis says.

"This could be important because if a person has an abnormal array of lipids, they might have abnormal proteins and this leads to dysfunction in the hippocampus where memories are made.

"We also know lipids are really important, for instance, in stabilising cell membranes and allowing cells to produce and use neurotransmitters properly - this is something that allows us to see exactly where in the brain things are going wrong."

The team were eventually able to identify specific types of lipids that were much more abundant in a normal brain than in one affected by Alzheimer's.

The molecular picture they created offered a better insight into the role of lipids - and a was a valuable contribution to global Alzheimer's research efforts.

3. Can our brain repair itself?

Auckland University brain researcher Dr Kathryn Jones.

We know that after the adult brain is injured - or even when battling a neurodegenerative disease - it can attempt to repair itself using neural stem cells found in specialised regions.

The potential here is phenomenal, yet most damaged neurons in the brain go unreplaced.

It was this promise that led Brain Research New Zealand research fellow Dr Kathryn Jones to investigate a rodent model of Huntington's disease, and a gene therapy approach that used viral vectors containing a neural-promoting gene.

The researchers found they could increase the number of "newborn" neurons that migrated into the brain area where cells were being lost - and even extend this repair process for longer than had been previously observed.

"This opens the possibility for enhancing brain regeneration after injury or disease," says Jones, who collaborated on the study with Auckland University colleague, Associate Professor Bronwen Connor.

"We managed to enhance the normal neurogenic process that was occurring from stem cells found in the adult brain."

Along with slowing or treating Huntington's disease, the strategy could potentially be used to enhance brain repair after a traumatic brain injury or stroke.

"However, for complete repair after injury, we still need to elicit a larger neurogenic response," she says.

"The focus is now on gaining a better understanding of what is stopping this endogenous response working as well as it could."

4 The protein that can boost memory

Otago University researcher Professor Warren Tate.

A certain type of protein may have the power to enhance memory.

Professor Warren Tate, who has just reported the discovery he made with Otago University colleague Professor Cliff Abraham in the journal Neurobiology of Learning and Memory, unlocked this secret by focusing not on the "villain" in Alzheimer's disease, but on a hidden and distantly-related hero.

The protein they developed in the lab, called "secreted amyloid precursor protein-alpha", was impressively able to restore memory mechanism in aged animals - indicating it could be a useful therapeutic target in Alzheimer's disease.

Much of the focus has been on a protein fragment known as beta-amyloid, regarded as the disease's causative agent, but Tate and Abraham looked at another piece of the same larger protein it was part of.

"Although what we are looking at is not as intensely studied as beta-amyloid, our view is that it's important because it's neuro-protective, and therefore might protect against neurological damage and ageing," Tate says.

"So we are looking at what you might call the good guy, rather than the bad guy."

Using the brains of aged rats, the researchers simulated what might happen in a human brain if the protein was supplied.

"We've done quite a lot of work on this and we've found that if you inhibit mammalian memory mechanisms and then provide the protein we've produced in our lab, it will actually reverse the effects, both in terms of electrophysiology - that is, measuring memory - and also behavioural learning.

"So we know it's important - and we know that it has restorative properties."

Watch this space.

5. What are the warning signs of dementia in Parkinson's disease?

In a cruel double-blow, most patients with Parkinson's disease also develop dementia over time.

What remains a mystery is the speed at which this happens.

Because the process is highly variable, making accurate predictions has been a tricky challenge for researchers.

For one team of Kiwi scientists, trying to get answers involved following the cases of 121 Parkinson's sufferers and crunching four years of longitudinal data.

Ultimately, they were able to pinpoint a specific criterion for mild cognitive impairment - a pre-dementia state - that yielded the highest risk of developing dementia within the period.

The team - Professor Tim Anderson, Dr Tracy Melzer, John Dalrymple-Alford and PhD student Kyla-Louise Horne - assessed the patients using 24 separate tests, searching for problems in the five different categories of cognitive impairment: memory, attention, decision-making, language, and awareness of space.

They discovered the best pointer to a patient with Parkinson's developing dementia in the following four years was that person failing two or more tests in any of the five categories.

The team believes their findings will help improve patient management and prognosis - and even lead to new therapeutic interventions targeted for patients at imminent risk of dementia.

6. The powerhouse protein to turn against Alzheimer's disease

Scientists have found what could be another big puzzle piece to tackling Alzheimer's - a mighty and intriguing protein called PSA-NCAM.

It effectively allows brain cells to remodel their shape and their connections with other cells and, importantly, it has also been linked to the disease.

Using adult human brain tissue from the Neurological Foundation Human Brain Bank, Auckland University PhD student Helen Murray and her colleagues revealed PSA-NCAM was produced by mature brain cells in specific regions of the adult human brain.

Its widespread distribution highlighted the incredible capacity of the brain to change and adapt throughout adult life, says the study's senior author, Associate Professor Maurice Curtis.

"This was interesting work that demonstrated many brain regions are geared up for plasticity."

Capable of rearranging itself in response to external stimuli, like a person's changing world, the PSA-NCAM allows brain circuits to be modified, enabling the addition of new memories throughout life.

The team compared the amount of PSA-NCAM in normal, Alzheimer's and Parkinson's disease brains, finding the protein decreased only in a specific region of the Alzheimer's disease brain involved in memory, and that this drop was linked to levels of toxic tau proteins.

Pinpointing this particular region, called the "entorhinal cortex", was crucial.

"It tells us there's one circuit in the brain that's really involved in Alzheimer's disease - and it's one that seems to be deficient in this key plasticity marker," Curtis says.

"That's really quite good in a way, because it gives us a target to focus on, something we can potentially manipulate."

7. Alzheimer's, Parkinson's... and the inner ear

Otago University researcher Professor Paul Smith.

Balance-related organs in our inner ear, called the "vestibular system", have been associated with higher cognitive functions like learning and memory.

Discovering more about these intriguing links has proved tough, however, simply because it has been difficult for scientists to navigate through the inner ear's bony labyrinth.

A new rat-based study focused on a surgical approach that effectively activates the individual sensors and nerves located in the inner ear could pave the way for an incredible new type of prostheses.

Such tiny devices - similar to cochlear implants to treat hearing loss - could potentially enhance memory and improve balance for Alzheimer's and Parkinson's disease patients and ageing populations.

Professor Paul Smith, who has been researching the concept with fellow Brain Research New Zealand principal investigator Dr Yiwen Zheng as part of a global collaboration, says the first "artificial vestibular systems" had been implanted in the past few years.

They worked by sensing head movement and electrically stimulating the nerves that normally supply nerves to the vestibular sensory receptors to provide the brain with the self-motion information it needed.

Over the past decade, it had become apparent this information - the result of a sensory system more than 500 million years old - was important for the "spatial memory" that tells us where we've been.

"We use vision and other sensory information as well, but the vestibular system is much older in evolutionary terms and therefore is a pivotal source of information for orientation in the world," Smith says.

Previously it was impossible to electrically stimulate specific parts of the system in small research animals like rats but Smith and his colleagues overcame the hurdle.

"We developed a surgical approach to selectively electrically stimulate all of the different receptor groups of the vestibular system in the rat - making it possible to investigate the effects of artificial vestibular stimulation on the brain and better understand the full consequences of vestibular implants for human patients."

8. What does stroke have to do with air pollution?

It turns out air pollution has been an under-appreciated factor in strokes, along with other surprising risks.

That was revealed by a global study spearheaded by internationally renowned stroke researcher Professor Valery Feigin, based at the Auckland University of Technology.

In developing countries, air pollution in the form of fine particulate matter accounted for about a third of the stroke burden, prompting Feigin and colleagues to argue cutting smog should be a big priority in these countries.

But in developed countries a noticeably higher burden of stroke was associated with behavioural and medical risk factors.

In these countries, the researchers revealed, it was more reasonable to focus on the reduction of behavioural risks - in particular, diet, physical inactivity and obesity - and the management of associated medical conditions.

Addressing these could improve health outcomes, reduce health-care costs and could arguably slash an individual's risk of stroke by about 80 per cent - and overall incidence by about 50 per cent.

"Our findings are important for helping national governments and international agencies to develop and prioritise public health programmes and policies," Feigin said.

"Governments have the power and responsibility to influence these risk factors through legislation and taxation of tobacco, alcohol, salt, sugar or saturated fat content, while health service providers have the responsibility to check and treat risk factors such as high blood pressure."

9. Why genetics could mean individualised treatment for Parkinson's sufferers

Researchers have been exploring the curious connection between the processes that cause Parkinson's disease and a gene known as SNCA.

The SNCA gene codes for a protein normally associated with healthy brain function.

Unfortunately, this protein sometimes misbehaves, forms unwanted aggregates and causes brain cells to fail and eventually die.

The result is Parkinson's disease.

The spread of the malformed protein across the brain also leads to progressive loss of many brain functions and even to dementia.

A global collaboration has already found subtle variations within the molecular structure of the SNCA gene were linked with dementia in patients with Parkinson's.

Other variations were also linked, but more commonly in patients without additional cognitive impairment.

These insights came from looking at the fine detail of the entire SNCA gene and how it varied across people with Parkinson's disease.

Brain Research New Zealand scientists involved in the global study are now leading an international effort to learn whether these genetic analyses can be combined with other clinical data.

Their new aim is to develop something that could provide accurate and individualised "risk scores" for future problems for those diagnosed with Parkinson's.

This could give doctors more information to discuss with patients when looking at treatment options, along with a better selection of participants for new drug trials.

10. Better blood flow could solve cognitive decline riddle

Otago University researcher Dr Liana Machado.

It's a question that has long baffled neuroscientists: why do some people show less cognitive decline than others as they age?

In a study led by Otago University researcher Dr Liana Machado, young and older adults were asked to complete cognitive tests while the study team measured blood-flow patterns in their brains.

As expected, older adults performed worse than young adults on the cognitive tests.

Yet the older adults also showed different blood-flow patterns, indicating they used more brain areas than the young adults while completing the cognitive tests - especially as the tests got harder.

Importantly, in the older adults, using more brain areas was associated with a better test performance, indicating the extra brain areas helped boost cognitive performance.

Now the researchers have established a relationship between blood flow and cognitive performance, Machado said it could be possible to help those not performing as well.

"Basically, if we can get the older adults who are having cognitive difficulties to increase their blood flow in the brain - particularly in the frontal lobe, which is where we saw the higher levels - then maybe we can help them perform better."

This could be done either through low levels of electrical brain stimulation, targeting the frontal lobe, or simply by encouraging them to engage in more physical activity, such as brisk walking, to improve their blood flow.

- NZ Herald

http://www.nzherald.co.nz/lifestyle/news/article.cfm?c_id=6&objectid=11702413