Discovering brain stem cells and waking them up with exercise

CSL Florey Medal

DSC_3314Professor Perry Bartlett is putting people with dementia on treadmills. He has already reversed dementia and recovered spatial memories in mice through exercise. During the next year he’ll find out if exercise will have the same impact on people with dementia. Then he’ll look at depression.

Underpinning these projects is the idea that the brain is constantly changing and that learning, memory, mood and many other brain functions are, in part, regulated by the production of new neurons. When Perry started exploring the brain in 1977, the mature brain was regarded as static and unchangeable. He challenged this dogma and his work has led to a transformation in our understanding of the brain.

In 1982 Perry predicted that there were stem cells in the brain. In 1992 he found them in mouse embryos then in adult mice. A decade later, he isolated them from the forebrain. His next big project was building up the Queensland Brain Institute from ten people to 500 in little more than a decade. Subsequently, the Institute has unleashed a new generation of neuroscientists whose discoveries range from using ultrasound to treat Alzheimer’s disease, to finding stem cells associated with mood, spatial learning and more.

Today, Perry is focusing on taking his latest discovery from mice to the clinic. He and the research team he mentors are preparing to start human trials to determine if exercise really can slow down or reverse dementia in humans. Dementia affects more than 300,000 Australians and many more cases are expected as our population ages. It’s a devastating condition and the direct cost to the community is more than $5 billion a year. The impact on families is beyond measure.

Perry receives the 2015 CSL Florey Medal for his revolutionary discoveries that have transformed our understanding of the brain and for his leadership of neuroscience in Australia.

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Professor Perry Bartlett qualified and worked briefly as a dentist. But along the way he was lured into immunology by a sense of adventure and the thrill of understanding something no one else understands.

After completing a PhD in transplantation immunology at The University of Melbourne, Perry studied cell biology at John Hopkins University, before moving on to University College London, where he worked under renowned immunologist-turned-neurobiologist Martin Raff.

It was here that he became interested in the interactions between the immune system and the brain, and made his first big discovery by creating the first monoclonal antibodies able to identify discrete populations of neural cells in the brain.

Coming back to Australia in 1978, he set up the first neuro-immunology lab in the world at the Walter and Eliza Hall Institute in Melbourne, where his work helped to overturn the idea that the brain was immune-privileged, that is, protected from the immune system.

Inspired by Professor Don Metcalf’s work on blood forming (haemopoietic) stem cells, in 1982 Perry published a paper predicting the presence of stem cells in the adult mammalian brain. “The idea that the brain was the only organ in adults, fixed and unable to repair and regenerate didn’t make sense to me,” says Perry.

So he set out to find stem cells. It took more than 20 years. In 1992, he was the first to prove the presence of stem cells in the forebrain of adult mice. Then in 2001, his team was the first to isolate them from adult mice. In the years since, his team has shown that the hippocampus contains many stem cells that are activated by neural activity to produce new nerve cells.

“We know that the hippocampus is vital for the formation of spatial navigation and remembering when and where activities occur. Our latest work suggests that many different groups of stem cells are at work in the hippocampus regenerating new neural connections,” says Perry. “We now understand that the brain is very plastic, changing all the time.”

“Our first thought back at the beginning was ‘Wow, now we will be able to repair the brain,’” says Perry. And, while it’s still been a long road, they are now well on the way.

“What excites me is that our initial discoveries nearly 25 years ago are now leading to potential treatments for dementia, and maybe for depression too,” say Perry.

The production of new nerve cells naturally slows down as we age. But Perry and his team have shown that the right amount of exercise in mice increases the production of new nerve cells and new neural connections in aged mice, reversing dementia and recovering spatial memory.

“After exercise an old animal that couldn’t find his way through a maze can now find his way just like a young animal,” he says.

In 2016 work will start on human trials to
determine if the result can be repeated and, if so, to then determine the right amount of exercise.

Returning to his immunology days, his team has also shown that the brain’s resident immune cells, microglia, appear to regulate the production of new nerve cells in response to exercise.

The team has identified the molecule regulating the microglia, fractalkine, and some of the molecules directly regulating the resident stem cells. These discoveries potentially open a new path for drugs against dementia.

If his personal research results weren’t enough, Perry has also played a massive role in the wider development of neuroscience in Australia. In 2002 he moved from Melbourne to Brisbane to establish the Queensland Brain Institute at the University of Queensland. In the past 13 years he has helped it grow from ten staff, to more than 500, attracting $87 million to build the Institute, $32 million in philanthropic contributions and, recently, $18 million in State and Federal support for the Clem Jones Centre for Ageing Dementia. That’s on top of winning $47 million in competitive grant funding for his own research programs.

As President of the Australian Neuroscience Society, he has forged links into Asia and, in 2010, established the first Joint Laboratory of Neuroscience and Cognition between QBI and the Chinese Academy of Sciences (CAS) Institute of Biophysics in Beijing. He went on to establish a further two joint laboratories, one with the CAS Institute of Automation in Beijing and another with the Second Military Medical University in Shanghai.

But fundamentally it’s the desire to understand the brain that has driven Perry’s research career. He says there is still much for the next generation of neuroscientists to discover.

“The brain is extremely complex,” he says. “There are 10,000 million neurons, each with 10,000 connections. My fascination for the brain comes from this complexity, how do these vast networks of circuitry determine the brain’s more metaphysical aspects like who we are, consciousness and our, so called, free will.”

Written by Toni Stevens and Niall Byrne, Science in Public, www.scienceinpublic.com.au

Further reading

www.qbi.uq.edu.au/group-leader-bartlett

www.aips.net.au/news-events/the-florey-medal

 

Professor Perry Bartlett

Qualifications

1975                      PhD (Transplantation Immunology), The University of Melbourne

1970                      BDSc (Dentistry), The University of Melbourne

Appointments

2003 – ongoing     Foundation Chair in Molecular Neuroscience, Queensland Brain Institute (QBI), The University of Queensland (UQ)

2003 – 2015         Inaugural Director, Queensland Brain Institute, UQ (stepped down as Director on 30 June 2015)

2003 – 2008         Australian Research Council (ARC) Federation Fellow, QBI, UQ

2002 – 2003         National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow, The Walter and Eliza Hall Institute of Medical Research (WEHI)

1997 – 2001         NHMRC Principal Research Fellow & Head, Development and Neurobiology Group, WEHI

1987 – 1996         NHMRC Senior Research Fellow and Head of the Laboratory of Neuro-immunology, WEHI

1982 – 1986         NHMRC Research Fellow, Cellular Immunology Unit, WEHI

1981 – 1992         Honorary Senior Research Fellow, Brain Behaviour Research Institute, La Trobe University

1978 – 1981         Senior Research Officer, Cellular Immunology Unit, WEHI

1977 – 1978         Medical Research Council Research Fellow with Professor M Raff, Department of Zoology, University College, London, UK

1974 – 1977         Research Fellow, with Professor M Edidin, Department of Biology, John Hopkins University, Baltimore, USA

Honours and awards

2014                      The Eccles Lectureship in Neuroscience, Australasian Neuroscience Society (ANS)

2014                      ANS Distinguished Achievement Award

2011                      Awarded one of NHMRC’s “10 of the Best Medical Research Projects in 2010”

2011                      Honorary Professor, Second Military Medical University, Shanghai, China

2009                      The Elaine G.C.F. Tso Memorial Lecture & Award, awarded by The University of Hong Kong, China

2002 – 2008*       NHMRC Senior Principal Research Fellowship

2003 – 2008*       ARC Federation Fellowship

2003                      Elected Fellow, Australian Academy of Science

2000 – 2002         Elected President, ANS

2000                      ANS Plenary Lectureship

2000                      Bethlehem-Griffith Research Medal and Prize for Neuroscience

1994 – 2002         NHMRC Principal Research Fellowship

1991                      Inaugural John Woodward Prize for Excellence in Neuroscience, awarded by the Australian Brain Foundation

* First person to hold both these prestigious awards simultaneously

 

The CSL Florey Medal

The Florey Medal is awarded biennially to an Australian biomedical researcher for significant achievements in biomedical science and/or human health advancement. In addition to the silver medal, the award currently carries a prize of $50,000 due to the generous support of CSL Limited.

This award was established in 1998 by the Australian Institute of Policy and Science in honour of the Australian Nobel Prize-winning scientist, Sir Howard Florey, who developed penicillin.

The Florey Medal is part of the Tall Poppy Campaign which aims to recognise and promote scientific and intellectual excellence in Australia.

Past winners are:

2013 – Professor Ruth Bishop

Discovery of rotavirus and the fight against this virus that has killed millions of young children through acute gastroenteritis.

2011 – Professor Graeme Clarke

Development of Australia’s bionic ear.

2009 – Professor John Hopwood

Diagnosis and treatment of genetically inherited disorders that affect children with clinical effects leading to progressive destruction of the brain and other organs.

2006 – Professor Ian Frazer

Research towards the development of vaccines against Human Papillomaviruses including cervical cancer and genital warts affecting the lives of millions globally.

2004 – Professor Peter Colman

Structural biology research, particularly for the discovery of a new class of anti-influenza drug.

2002 – Professor Colin Masters

Work relating to Alzheimer’ disease.

2000 – Professor Jacques Miller

Discovery of the function of the thymus which signalled a seminal contribution to immunology.

1998 – Dr Robin Warren and Professor Barry Marshall

Discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease.

The Australian Institute of Policy and Science (AIPS)

The Australian Institute of Policy and Science is an independent and non-partisan not-for-profit organisation first founded in 1932. They have grown with Australia’s public policy history and work to:

  • Increase public engagement in science.
  • Promote excellence in research, innovation and the promotion and communication of science.
  • Inform and influence policy and policy-making.
  • Invest in a scientifically inspired, literate and skilled Australia that contributes to local and global social challenges.

AIPS achieves its objectives through an extensive network of partners spanning university, government, industry and community actors.