Stimulating take on age-related dementia
July 25th 2009 21:43
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EVER had that awful feeling of forgetting just where in the car park you left your car? This kind of fleeting forgetfulness opens a small window into the dementia of old age, a condition where things go wrong in the laying down new memories, particularly memories of where and when things happened.
Helen Francombe | July 25, 2009
Article from: The Australian
Such age-related dementia would eventually happen to us all if we lived long enough, says Perry Bartlett, director of the Queensland Brain Institute.
But according to Bartlett, new research into stem cells in the brain shows the tantalising possibility of staving off age-related changes. It's also led to a shift in thinking about the permanence of dementia.
``We used to think it was an irreversible process, but now we think what is happening in the brain is more like a machine running down, and the good news is that we think it can be reversed, and this really is a brand-new concept,'' he says. In a nutshell, Bartlett says, it's all about harnessing the brain's power for self-renewal, which comes down to stimulating the natural ability of stem cells in the brain to create new neurons, or brain cells.
Healthy brains continually make new neurons, the nerve cells that store new memories. That's why a good supply of neurons is essential for good brain function and mental health, says Bartlett, noting that evidence is mounting that ageing dementia could be caused by a slowdown in the production of new neurons.
One way of kick-starting the stem cells in ageing brains is with exercise, according to new research from Bartlett's QBI colleague Dan Blackmore.
Speaking of Blackmore's work, Bartlett says: ``By the time a mouse is 18 months old _ equivalent to a human 65 year old _ it is making only about 10 per cent of the number of brain stem cells as it did when it was a young buck, and this same decline is apparently also happening in humans.''
Blackmore has discovered that mice that voluntarily exercise in a running wheel are protected from this age-related decline.
``Dan's study was very surprising because even if you ran mice only in their early life, they still showed an increase in brain stem cells when they got much older, pointing to the fact that exercise is a pretty good way of forward-proofing your brain stem cells for future years,'' says Bartlett.
What makes stem cells special is their ability to create large numbers of other types of cells.
``Their real feature is that when they divide they not only create a new cell but also one daughter cell remains as a stem cell _ so even an ageing brain like mine has some stem cells _ and this ability for self-renewal is a stem cell's hallmark,'' Bartlett says.
There are two main types of stem cells: embryonic and adult. Embryonic stem cells can develop into any cell type in the body. By contrast, adult stem cells have a more limited repertoire, usually making only the same type of cell _ say, heart or brain cells _ as the tissue in which they're found.
According to Bartlett, two parts of the brain are particularly busy making stem cells, the olfactory bulb and the hippocampus. The hippocampus is where a lot the action happens when people lay down new memories. It lies below the cortex and is shaped like a seahorse (the Greek word for seahorse gives the hippocampus its name) and plays a vital role in brain function.
``It is one of the first stops for inputs from our environment into our brains. For example, visual, auditory, olfactory and emotional input all congregate here, and that is where memories associated with these environmental cues are first imprinted,'' Bartlett says.
He says the hippocampus is responsible for spatial learning, such as remembering when and where events occur; for instance, those ``where did I leave my keys?'' moments.
``There is also a lot of anecdotal evidence that the size of the hippocampus correlates well with cognitive ability. If people have kept their brains very active, say by learning new languages, travelling and so on, they seem to have less shrinkage of the hippocampus as they age.''
The implication is that the age-related decline in stem cell activity and shrinkage of the hippocampus may be due to a lack of stimuli. If so, stimulating the brain through exercise _ physical and mental _ promises to be a powerful strategy for combating dementia. What's more, work by QBI researcher Tara Walker suggests it may be possible to design a drug to do the same thing. She already has identified the chemical messengers responsible for revving up the stem cells in the hippocampus after exercise.
As Bartlett says: ``They will become frontline therapeutic agents in our attempts to overcome ageing dementia and, together with exercise, I really think they are going to revolutionise our approach to preventing and potentially reversing dementia.''
While Bartlett and company seek to gee-up stem cells already present in the brain, Richard Boyd, director of Monash Immunology and Stem Cell Laboratories in Melbourne, wants to import stem cells. Right now Boyd is working with colleagues at the University of California, Irvine, who are transplanting brain cells to treat Alzheimer's disease.
Their project was among the first to be funded under the new international alliance between the state of Victoria and the California Institute of Regenerative Medicine, headed by Alan Trounson, founder of the Melbourne-based Australian Stem Cell Centre. The UC scientists work with a strain of mice bred to develop Alzheimer's disease. The researchers have seen improvements in cognitive recognition after injecting brain stem cells into their pre-aged mice.
``In Alzheimer's disease we know there is a build-up of plaques in the brain and this paralyses the nerves,'' Boyd says. ``Interestingly, how the stem cells deliver the positive message is still not precisely known; maybe directly, maybe by growth factors (that) talk to the patient's own brain stem cells.''
He suggests that the stem cells may not obviously reduce the plaques seen in Alzheimer's disease. Rather, they may stop them getting any bigger. They also may stimulate the growth of new, healthy neurons around the plaques.
Exciting as this is, there is a large stumbling block to successful stem-cell transplants in humans: Homo sapiens' effective immune systems. ``Our T-cells (a type of immune cell) destroy foreign stem cells, just as they would a bacteria or virus,'' Boyd says.
His work hinges on tricking the thymus _ the engine room of the immune system _ into making T-cells that don't see transplanted stem cells as foreign. His approach is to inject blood stem cells from the intended brain stem-cell donor first. This re-educates the immune system so it thinks the donor brain stem cells are home grown, leaving them alone to get on with repairing the brain.
Boyd's California colleagues presented new results earlier this month at the International Society for Stem Cell Research conference in Barcelona. Another MISCL team also reported new findings in Barcelona.
That group studies stem-cell treatment for multiple sclerosis, an auto-immune disease in which the immune system destroys the nerve cells that make myelin, a substance that acts like the plastic coating on wires that stops short circuits.
Claude Bernard is group leader of the Multiple Sclerosis Research Laboratory: ``The loss of myelin around nerves in the spinal cord and brain leads to the symptoms such as paralysis and vision problems in MS. And although we do have some treatments that can give patients a reprieve for a while, it is still an incurable condition.''
Still, Bernard claims his research shows heartening results. Stem-cell transplants into mice with an MS-like disease have shown their symptoms, such as paralysis, are much reduced. It appears the transplanted stem cells stimulate some self-repair of the brain, possibly by attracting the mouse's own stem cells to the area of injection.
``And as an unexpected bonus the transplant also seemed to have its own immunosuppressive effect that may prevent further destruction by the nasty immune cells that cause the damage in MS,'' Bernard says.
It's an exciting time in stem cell research that holds the promise of new ways to combat neurological and mental illnesses, Bartlett says: ``Once we find the keys to unlock the potential of brain stem cells to create new neurons, we may be able to apply these approaches to other conditions such as depression, stroke, trauma or neurodegenerative diseases such as motor neurone disease.''
link to the Article reproduced here
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